Introduction to Neuroscience (Part 2) - 2014

Myotactic Reflex

classic knee jerk reflex when the hammer hits the patellar ligament what it is actually doing is stretching the muscle above it the muscle spindle is going to stretch and fire the Ia afferent neuron ∙this is exactly the same pathway as the monosynaptic stretch reflex the action of the inhibitory interneuron is just going to allow the heteronymous muscle to stretch, and prevents this muscle from countering the effect of the homonymous muscle

Somatotropic Organization

how do we know portions of cortex are involved in movement? ∙movement observed when portions of cortex stimulated with probes ∙moves were seen contralaterally to area of brain stimulated Somatotropic organization of the primary motor cortex ∙most laterally - tongue ∙medial, ventral portion - face ∙superior to face portion (still lateral) - hand and trunk ∙inside longitudinal fissure - leg

Motor Basal Ganglia

if the direct and indirect pathways are in complete balance, it does not mean that there is no motion, but rather that there is an elegant balance b/w the two pathways ∙the MSNs of one pathway may fire more rapidly, so that these neurons overcome the signals from the other pathway, leading to motion or inhibition of motion

Key Similarities b/w Olfactory System and Gustatory System

regeneration ability is shared by both olfactory receptors/cilia, as well as taste receptors neurons in both olfactory and gustatory systems are bipolar

Circumventricular Organs

sites where the blood-brain barrier is incomplete these are sites of neurosecretion and sites for sensory input to come in based on information from blood: ∙median eminence (parvocellular neurons synapse on blood vessels) ∙neurohypophysis (posterior pituitary cells secrete oxytocin and ADH) ∙organum vasculosum of lateral terminalis (OVLT) and subfornix - does osmoreception and Na reception ∙pineal gland (only mentioned)

Cerebrum

cerebrum has 3 types of cortex ∙in this lecture we focus on the neocortex Neocortex (isocortex) ∙6 layers (top layer near meninges, bottom layer near white matter of the brain ∙function: primary sensory, motor cortex and association cortex Allocortex (paleocortex) ∙3-5 layers ∙function: entorhinal cortex, piriform cortex Archicortex ∙3 layers ∙function: hipoocampal formation (location is in the hippocampus)

Acute Stress

"good" stress (Acute stress) is classified as experiences that are of limited duration, can be "mastered" and that leave a sense of accomplishment ∙this type of stress pushes you to complete task acute stress response evolved as a response to an immediate threat

Key Differences b/w Olfactory System and Gustatory System

while olfactory neurons are organized into glomeruli in the olfactory bulb, taste receptors on "taste cells" are organized into taste buds ∙taste buds are then organized into papillae ∙notice that taste cells form a synapse with gustatory afferent axons, which comes from the 3 cranial nerves once taste is detected by taste cells, the cell can be depolarized directly by the influx of cations through Na+ or H+ channels (ionotropic) OR linked to a GPCR (metabotropic) ∙certain tastes rely only on ionotropic channels, some only on metabotropic and other will use both ∙regardless of combination, activation of channels will lead to depolarization ∙instead of transmission of an AP as with olfactory system, there is release of serotonin

Differences in Gray Matter Across Cross Sections

within the spinal column, motor neurons are topographically organized ∙alpha motor neurons are large and generally distributed in the anterolateral region of the ventral horn and have larger nuclei ∙in regions with larger distributions of alpha motor neurons, the ventral horn will be larger the appearance of gray matter varies at different spinal levels (and white matter tends to disappear as we descend) ∙cervical - large ventral horns due to innervation of upper limb muscles, takes on a X shape, lots of white appearance, appearance of cuneate fasciculus thoracic - small ventral and lateral horns, H-shaped, lots of white matter ∙lumbar - large ventral horns ∙sacral - relative lack of white matter compared to gray matter, lateral horns contain sympathetic imputs, appearance of the gracile fasciculus

Brodmann's Area of Cortex

1 = somatosensory 2= somatosensory 3= somatosensory 4 = primary motor 6 = secondary motor 17 = primary vision 18 = secondary vision 22 = class language (Wernickes) 39 = Angular gyrus 40 = submarginal gyrus 41 = primary auditory 42 = secondary auditory 44 = speech/grammar (Brocas Area) 45 = speech/grammar (Brocas Area)

Pain Receptors

2 major classes of pain receptors: ion channels and G protein coupled receptors ∙ion channels open quickly and G protein receptors have a slower response and are probably more involved in sensitization as opposed to direct activation ∙virtually every molecule that acts on an ion channel also has a counterpart G protein receptor two receptors that are mostly commonly involved in inflammatory pain are the capsaicin receptor (TRPV1) and the mustard oil receptor (TRPA1) ∙TRPV1 receptor is expressed in sensory nerves (C fibers) →it is a polymodal channel that sense multiple noxious stimuli →it is activated by capsaicin, thermal heat (above 43°C), protons, and chili peppers (via a fatty agonist generated in the body) →if you take out this receptor in a mouse, it senses no inflammatory pain at all →the TRPV1 receptor is key b/c it responds to many stimuli →it is thought that phosphorylation of the receptor is important to the process of sensitization →often there is cross talk b/w many of the TRPV1 receptors and G protein receptors → activate protein kinase C which causes receptor sensitization ∙TRPA1 is expressed in sensory nerves (C fibers) →receptor is activated by isothiocyanates in mustard oil and wasabi and cinnamon aldehydes (hot tamales) →it is the receptor responsible for crying when you cut and onion b/c it causes a release of volatile chemicals that travel to the cornea

Autonomic Nervous System

2 neuron hookup system consisting of preganglionic and postganglionic neurons ∙generally, preganglionic neurons have cell bodies in the CNS with exiting axons that synapse with postganglionic neurons synapse is called the ganglia and the postganglionic neurons go on to innervate smooth muscle, cardiac muscle, or glands throughout the body juxtaposing the exiting axons from the CNS are corresponding entering axons from the periphery ∙known as general visceral efferents (exiting/motor) and afferents (approaching/sensory) ∙general visceral efferents have preganglionic neuronal cell bodies that originate in the lateral horn of the spinal cord for the SNS ∙general visceral afferents return to the dorsal root ganglion outside the spinal cord before entering it these are unique in that they are pseudounipolar neurons with one process in the peripheral nervous system and one in the central nervous system ∙appear like bipolar neurons but both processes originate form one process exiting the cell body preganglionic neorons are myelinated by Schwann cells, whereas postganglionic neurons are unmyelianted ∙makes postganglionic neurons weak, meaning they need to hijack a blood vessel or another nerve in order to reach target organ

Neuroendocrinology of Acute Stress

2 systems activated during stress response: HPA axis and SNS HPA Axis ∙final common pathway in mediation of stress response ∙briefly, PVN in hypothalamus secretes CRH (and vasopressin) which stimulate release of ACTH from AP, which stimulates adrenal cortex to produce cortisol ∙cortisol promotes glycogenolysis, immunosuppression, and suppression of stress response after threat has passed via long-loop feedback on hypothalamus (CRH) and AP (ACTH) ∙in brain, cortisol acts on amygdala and hippocampus, while CRH is connected with regions that control body temp, suppress appetite, and control pain ∙during acute stress response, corticosteroids can enhance cognitive processes, affect mood and motivation and promote excitability/neuroprotection SNS ∙innervates every organ, blood vessel and gland in body ∙SNS neurons release EPI and Ne, which complement effects of cortisol during times of stress →effects are in glycogenolysis, vasoconstriction, increasing HR, increasing BP, diversion of blood to brain/heart/SM, increased metabolism, bronchodilation and activation of amygdale important: action of amygdala on hypothalamus stimulates SNS

Types of Feedback From Intrafusal Muscle Fibers

2 types of feedback from intrafusal muscle fibers: Group Ia (primary afferents) and Group II (secondary afferents) Group Ia wrap all the way around the muscle spindle fibers and terminate in annulopsiral endings ∙detects dynamic movements and rate of stretch while it is occuring Group II receptor endings are called flower spray endings and are very different than Group Ia ∙provide information about the total degree of stretch in the muscle and will cause a constant firing in proportion to the degree of stretch at any point in time in the muscle The Golgi Tendon Organ (GTO) is located in a capsule b/w a tendon and muscle fibers ∙w/in the capsulare are copious amounts of collagen fibers intertwined with Group Ib afferent neurons ∙this section of the apparatus gives information on the degree of contraction of the muscle and is located in series w/ muscle fibers

Connectivity Afferents and Efferents

Afferents (Inputs) ∙specific afferents: these afferents are thalamocortical projections that end densely on stellate cells in layer 4 →have topographic organization from the thalamus to cortex (meaning there are different nuclei w/in thalamus that each project to different parts of cortex) ∙Nonspecific afferents: not tested Efferents (Outputs) ∙commissural: connect layer 3 to contralateral (opposite side) cortex →note: commissure means any bundle of white matter that connects the two hemispheres ∙associational: connect layers 2 and 3 to ipsilateral (same side) cortex, can either be short or long connections →short connections: arcuate fibers to adjacent gyrus →long connections: arcuate fasciculus and other tracts ∙Corticofugal →from layer 4 to thalamus →from layer 5 to various non-cortical structures

Function of the Hypothalamus

Anterior - A1 Slice ∙involved in homeostatic mechanisms: control BP, blood composition, body temp, hormone secretion, and reproductive activities ∙the suprachiamatic nucleus (SCN) plays major role in setting the diurnal/circadian rhythms and maintaing our physiologic link with what time of day it is →what makes you confused when you're jet lagged →great example of integrative nature of HT - it has to take signals directly from retina and modulate body's hormone levels, activities, etc. accordingly ∙supraoptic and paraventricular nuclei have the magnocellular cells which project to the posterior pituitary and release vasopression and oxytocin →key point: ANTERIOR hypothalamus to POSTERIOR pituitary ∙lamina terminalis is sometimes categorized as part of the HT due to role in water intake →receives projections from PVN or pre-optic nuclei, and sends proojeections to brain stem Rostral Ventrolateral Medula (RVLM at C7) which controls HR →not truly a part of the HT Medial - A2 Slice ∙has a variety of functions, particularly control of the anterior pituitary via the parvonuclear cells →nuclei pertaining to regulating anterior pituitary are known are tuberal nuclei ∙arcuate nucleus has a neuroendocrine role through release of dopamine, which inhibits release of prolactin, and release of GHRH →also projects elsewhere in CNS to regulate feeding, sexual behaviors and regulate autonomic nervous system in ascending and descending tract of spinal cord ∙dorsomedial and ventromedial nuclei play a role in feeding behaviors and aggressive behaviors →loss of ventromedial nucleus results in hyperphagia, while loss of dorsomedial nucleus results in anorexia →maintain food intake set point →dorsomedial nucleus can also be hyperactive in range → has afferent/efferent pathway w/ amygdala which brings the fear/limbic emotion information into equation Posterior - A3 Slice ∙posterior region is involved in complex functions, projects to other brain regions ∙posterior nucleus is involved in temperature regulation ∙mammillary bodies are involved in formation of procedural memories through projections to and from the hippocampus →also histaminergic and involved in sleep-wake cycle by promoting wakefulness/arousal

Major Corticofugal Pathways

Corticospinal - generated in cortex, terminates in spinal cord, controls all muscles in body but face Corticobulbar - generated in cortex, terminates in brainstem, controls muscles of face

Ascending Sensory Pathways

DCML and ALS form the ascending sensory pathways dorsal column ledial lemniscus pathway (DCML) carries touch, pressure and conscious proprioception ∙information that comes in from Group I and II fibers pain fibers (Aδ and C) will form the anterior lateral system (ALS) the rootlet fibers enter into the spinal cord over a fairly wide distance that spans both the white and gray matter ∙the Aα and Aβ fibers don't enter the spinal cord at the same place as the Aδ and C fibers →Aδ and C fibers are lightly myelinated, enter more laterally, and go into the dorsal horn directly →the Aα and Aβ fibers enter more medially and since they are heavily myelinated the location of their entry point cannot be determined with accuracy →also, b/c Aα and Aβ are more medial, they have access to dorsal columns, and the dorsal colums are part of the DCML

Stress Related Disorders

Depression ∙chronic mental disorder characterized by some of all of following: →low mood, low self-esteem, self-hatred, loss of interest/pleasure, poor concentration/memory, low sex drive, thoughts of death/suicide, insomnia ∙biological mechanisms that lead here are unclear but affects women more than men, runs in families, affects 20% of population ∙presumed to result from interaction b/w environmental stress and genetics, stress does not cause depression, it is only a risk factor for it ∙HPA is final common pathway for major part of depressive symptomatology (i.e. hyperactivity: high CRH and cortisol levels) →hyperactivity of HPA axis has been shown to be associated with genetic mutations and indicates increased risk of relapse after recovering from depression ∙antidepressants work by normalizing HPA axis Anxiety ∙normal rxn to stress, but when symptoms become chronic, anxiety becomes a disorder ∙associated w/ hyperactive stress responses mediated by overabundance of catecholamines PTSD ∙PTSD is a type of anxiety disorder that may occur after a traumatic event ∙thought to be due to failure to contain stress response at time of trauma → leads to irrepressible activation of stress response at that time ∙symptoms can be divided into 3 categories: avoidance and numbing, intrusive memories, and anxiety/increased emotional arousal ∙neuroendocrine profile of PTSD is different from depression →see high CRH w/ low cortisol →low cortisol thought to be due to enhanced sensitivity of anterior pituitary and hypothalamus to negative feedback from low amounts of cortisol ∙PTSD has reduction of corticosteroids and increase in catecholamines ∙3 brain areas affected: hippocampus, PFC and amygdala →if experience is extremely traumatic, a memory from that experience may never be recorded properly →this suppression of hippocampus leads to formation of flashbulb memories which make person feel like he/she is reliving event →suppression of PFC suppresses ability to regulate fear →hyperactivation of amygdala secondary to insufficient top-down control from PFC and hippocampal structures is required for formation of flashbulb memories by hippocampus

Dorsal vs. Ventral Pathways

Dorsal → WHERE PATHWAY Ventral → WHAT PATHWAY generally tracts in the superior (dorsal) regions of the brain help us determine where something is, whereas the inferior (ventral) regions of the brain help us determine what something is ∙occipital lobe - inferior and anterior inferior regions are involved in recognition → "what something is" ∙parietal lobe - superior parietal lobule is all about spatial processing

4 Key Afferent-Efferent Pathways in Hypothalamus

Fornix ∙projection b/w hippocampus and mammillary bodies ∙procedural learning memory ∙also known as the Papez circuit Stria terminalis ∙projections b/w amygdala (limbic system) and dorsomedial nucleus/medial nuclei ∙plays a role in linking feelings, like rage, to our instincts, like the need to eat Medial-Forebrain bundle ∙projections b/w anterior and medial hypothalamus and septal nuclei/frontal cortex ∙involved in inhibitory signal from cortex to hypothalamus ∙found to be damaged in Alzheimer's and frontal temporal dementia Thalamomammillary/Mammillothalamic tract ∙projections b/w mammillary bodies and anterior thalamus and from there to higher brain regions/cortical regions ∙plays role in social information of instinctual behavior, like waiting to go to the bathroom

Hypothalamus Anatomy

HT is made up of multiple nuclei, which are mostly named based on location and have multiple functions ∙IT IS MOST IMPORTANT TO UNDERSTAND THE NATURE OF THE HT AS AN INTEGRATIVE STRUCTURE the location of the HT in a strategic location right next to the thalamus, sitting just above the midbrain and right next to the cortex ∙allows it to integrate somatosensory, cortical and limbic inputs in order to maintain homeostasis through hormonal and neural mechanisms and to regulate living behaviors like feeding, reproduction, rage, defense, etc. main way we look at anatomy of HT is by anterior, medial and posterior slices Anterior - A1 Slice ∙aka pre-optic region, since it is in front of the optic nerve ∙starts with anterior commissure ∙we have the suprachiasmatic nucleus (resting above optic chiasm), the supraoptic nucleus, the anterior hypothalamus (anterior most) and the paraventricualr nucleus (around the lateral ventricles) ∙the magnocellular cells project from this region to the posterior pituitary ∙lamina terminalis is sometimes considered to be a part of the HT as well Medial - A2 Slice ∙marked off by the infundibular recess (aka tuber cinereum or median eminence) ∙labeled at the infundibular recess, is the point from which the pituitary descends ∙here we have the arcuate nucleus (extension of the arcuate fibers from lower part of the brain stem), ventromedial nucleus, and dorsomedial nucleus ∙these 3 are the middle nuclei and get bigger moving from arcuate nucleus to dorsomedial nucleus ∙parvocellular neurons from this region to the anterior pituitary Posterior - A3 Slice ∙here are the mammillary bodies and the posterior nucleus (posterior most nucleus) ∙mammillary bodies are functionally part of the limbic system but anatomically part of the HT ∙they receive projections via the fornix from the hippocampus

Magnetoencephalography (MEG)

MEG is similar to electrophysiology methods relies on the fact that electrical currents generate magnetic fields device measure magnetic fields associated with electrical activity of neurons ∙therefore has same pros and cons as electrophysiology pros - good temporal resolution cons - bad spatial resolution (a litter better than ERP)

Functional Neuroimaging

PET and fMRI functional neuroimaging is an indirect measure of brain activity where you measure changes in blood flow or oxygenation levels to regions of the brain which correlate with changes in neuronal activity Methods ∙Positron Emission Tomography: patient consumes radio-labeled molecules which are then detected by PET scanner ∙Functional Magnetic Resonance Imaging (fMRI): does not use radiation, rather it detects changes in magnetization associated with blood flow to different structures in the brain Pros: good spatial resolution (especially fMRI) → spatial resolution is the ability to distinguish a specific location for the brain activity) Cons: poor temporal resolution - blood response ∙temporal resolution refers to the amount of time of neuronal activity that can be separated out of the scanner ∙these methods basically rely on brain recruiting nutrients (oxygen, glucose) in order to perform tasks ∙there can be a few seconds lag time b/w brain performing task (e.g. reading) and when the changes detected by PET or fMRI occur

Parasympathetic Nervous System

PSNS is also known as the cranio-sacral system b/c of the location of its cell bodies in the rain stem, as wella s the sacral portion of the spinal cord ∙cranial outflow travels on CN III, VII, IX, and X ∙form 4 PSNS ganglia ciliary ganglion receives preganglionic fibers from the Edinger-Westphal nucleus in the brain stem and travels along CN III (oculomotor) ∙postganglionic fibers continue to the eye to innervate the ciliary and pupillary constrictor muscles ∙pupillary constrictor muscles are opposed by the SNS innervation of the pupillary dilator muscles pterygopalantine ganglion receives preganglionic fibers from the lacrimal nucleus of the brain stem ∙they travel along CN VII (facial) and the postganglionic fibers innervate the lacrimal and nasal glands submandibular ganglion receives preganglionic fibers from the superior salivatory nucleus that travel along CN VII (facial) ∙postganglionic fibers innervate the submandibular and sublingual glands the optic ganglion receives preganglionic fibers from the inferior salivatory nucleus and travel along CN IX (glossopharyngeal) ∙postganglionic fibers go to the parotid gland preganglionic fibers originating from the nucleus ambiguous travel along CN X (vagus) to innervate heart preganglionic fibers originating from the dorsal nucleus of the vagus nerve travel along CN X and innervate the remaining thoracic and abdominal viscera (GI tract up to left colic fixture) sacral outflow exits from the ventral horn of the sacral spinal cord and travels on sacral nerves S2-S4 ∙known as pelvic splanchnic nerves ∙innervate GI tract from left colic fixture onward, as well as pelvic viscera

Eye Pathways

SNS ∙preganglionic fibers ascend from upper thoracic spine (T1-2) and synapse in the superior cervical ganglion ∙postganglionic fibers travel along the internal carotid artery and pass through the ciliary ganglion ∙continue to eye via short ciliary nerves PSNS ∙preganglionic fibers from the Edinger-Westphal nucleus travel along the oculomotor nerve (CN III), synapse in ciliary ganglion and travel to eye via short ciliary nerves

Lacrimal Gland Pathways

SNS ∙preganglionic fibers ascend from T1-2 and synapse in the superior cervical ganglion ∙then follow internal carotid artery to deep petrosal nerve (just SNS) and join the great petrosal nerve) ∙continue as the nerve of the petrygoid canal, which included postganglionic sympathetic and preganglionic parasympathetic fibers PSNS ∙preganglionic fibers from the superior salivatory nucleus travel along the facial nerve (CN VII) to the great petrosal nerve (just PSNS) ∙these are preganglionic PSNS fibers that join SNS fibers to form the nerve of the pterygoid canal, leading to the pterygopalatine ganglion

Parotid Gland Pathways

SNS ∙preganglionic fibers from T1-2 ascend and synapse in the superior cervical ganglion ∙post ganglionic fibers travel via the external carotid artery to the parotid gland PSNS ∙preganglionic fibers from the inferior salivatory nucleus travel along the glossopharyngeal nerve (CN IX) to the tympanic nerve ∙this continues to the lesser petrosal nerve and the otic ganglion ∙here they synapse and the postganglionic fibers continue via the auriculotemporal nerve to the parotid gland

Submandibular and Sublingual Salivary Gland Pathways

SNS ∙preganglionic fibers from T1-2 ascend and synapse in the superior cervical ganglion and travel along the external carotid artery to the maxillary artery to their destinations PSNS ∙preganglionic fibers from superior salivatory nucleus of the brain stem travel along the facial nerve (CN VII) to the chordi tympani nerve ∙this joins with the lingual nerve and continues onto the submandibular ganglion ∙here the fibers synapse and the postganglionic fibers continue onto their destinations ∙the chorda tympani also carries afferent taste sensation for the anterior 2/3 of tonue back to CNS ∙along with great petrosal nerves, the chorda tympani innervates the salivary glands

Sympathetic Nervous System

SNS is also referred to as the thoraco-lumbar system, due to cell bodies of SNS neurons residing b/w T1 and L2/L3 axons exit the lateral horn aspect of the spinal cord and form dorsal and ventral primary rami ∙these rami then branch further to innervate entire body SNS preganglionic neurons have several options for synapsing ∙can enter the sympathetic chain ganglia via myelinated white rami communicantes at the same level and then exit via unmlyeinated gray rami communicantes to form spinal nerves ∙can enter the sympathetic chain ganglia and ascend/descend and synapse at a different level ∙last option is to enter sympathetic chain ganglia and exit w/o synapsing →entail splanchnic nerves that serve various organs in thorax and abdomen →these particular preganglionic neurons synapse closer to the organ in prevertebral ganglia SNS innervation occurs bilaterally ∙to serve head, neck and face, axons originating from the superior portion of the thoracic spine can ascend and synapse at levels superior to T1 ∙likewise, inferior axons can descend and synapse at levels inferior to L3 How splanchnic nerves innervate different organs ∙cardiopulmonary nerves synapse in the cervical region of the sympathetic chain ganglia and form plexuses that serve the head, neck and thorax →examples given were the ciliary ganglion, submandibular ganglion, pulmonary plexus and cardiac plexus →these have short preganglionic fibers and longer postganglionic fibers ∙the thoracic splanchnic nerves include the greater, lesser and least splanchnic nerves serving the abdominal organs →these form the 3 major ganglions of the abdomen: celiac, superior mesenteric and inferior mesenteric →these ganglia are much closer to the target organ which gives larger preganglionic fibers and shorter postganglionic fibers exception to sympathetic innervation is the adrenal medulla ∙arises from neural tissue and is therefore a secretory organ and is equivalent to a postganglionic neuron ∙its preganglionic neuron directly innervates the adrenal meddula for systemic release of epinephrine and norepinephrine

Subthalamic Nucleus

STN lies ventrally to the thalamus and superiorly to the SN ∙no discoloration to help locate it, so you have to know its general location receives input from the cerebral cortex's motor areas ∙if we have a lesion in this area blocking regulation of the thalamus, there will be much more motion than usual it is glutamatergic projects to the SN and GPi b/c it is almost constantly inhibited by the GPe, it is usually inactive, but it is spontaneously active and will signal strongly if that inhibited is removed note that the STN is connected to both the GPe and GPi ∙when STN is not inactivated by the GPe, it actually leads to further inhibition via the GPi

Vision function can be divided into 3 categories

Scotopic is when the luminance is very low (darkness to just before starlight) mesopic is form starlight to somewhere in between moonlight and indoor lighting ∙in this zone, cone threshold is reached so you get both the rods and cones responding, and there is the beginning of color vision Photopic starts at a luminance of just before indoor lighting ∙in this zone you have rod saturation so it drops off, allowing for the highest resolution with color vision and the best acuity ∙at the highest levels of luminance you can end up with photoreceptor damage

Diseases of the Dorsal Root Ganglia

Syringomyelia is the expansion of the central canal and loss of ALS sensation at that level ∙will cause problems in the region where the ALS decussates and so you will have loss of sensation on both sides of the body ∙generally occurs in the cervical region and affects the upper limbs ∙dorsal columns are unaffected Neurosyphilis affects the large dorsal root ganglia in the lower half of the body leading to degeneration of the fascicularis gracilis (Dorsal column) ∙there is selective degeneration of the highly myelinated fibers of the DRG

Hair Cell & Vestibular Organization

Type I & type II hair cells both contain kinocilia and sterocilia Type I hair cells contain an afferent nerve fiber that forms a cup around the hair cell, which increases the sensitivity and amplifies the signal ∙the efferent nerve fiber synapses on the afferent nerve fiber ∙type I hair cells are located closer to the middle of cupula Type II hair cells contain a smaller afferent nerve terminal and the efferent nerve fibers synapses directly onto the hair cells ∙type II cells are located closer to the edges of the cupula macula is the vestibular area that contains specialized sensory hair cells, and the otolithic membrane encapsulates the kinocilia & stereocilia, and contains calcium carbonate crystals to increase its inertial mass ∙2 vestibules are on each, one for each utricle and saccule, which detect translational acceleration in the horizontal and vertical plane, respectively ∙additionally, we have 3 semicircular canals, each orthogonal to the others, to detect rotational acceleration in 3 dimensions vestibular apparatus is made up of the 3 semicircular canals, utricle and saccule ∙located just posterior to each ear

Elongated Nuclei

a single muscle will have a tightly distributed set of motor neurons within the the spinal cord know that these work closely to ensure efficiency of contraction

Neuroanatomy

anterior to the central sulcus is the precentral gyrus (Brodmann area 4) which contains the primary motor cortex (M1) primary somatosensory cortex is found posterior to the central sulcus in the postcentral gyrus (Brodmann areas 1, 2, 3) ∙this area plays a role in movement since it receives sensory feedback from muscle in front of the precentral gyrus is Brodmann area 6, which is subdivided into the premotor area (PMA) laterally and the supplementary motor area (SMA) superiorly Brodmann areas 5 and 7 in the posterior parietal cortex are also involved in movement, particularly in integrating sensory information Brodmann area 8 is involved in the conjugation of the eyes

Retinogeniculostriate Pathway

after the ganglion cells transform visual inputs, the signal is transmitted through the optic nerve to the lateral geniculate nucleus (LGN) of the thalamus and then to the striated cortex (V1-primary visual cortex) the LGN is the primary relay center for visual input and signals in the LGN are segregated by eye and cell type in 6 different layers there are 2 pathways that leave from the LGN: magnocellular pathway (large cell body) and the parvocellular pathway (small cell body) ∙each of the pathways responds to different prioperties and is optimized for different aspects of vision ∙bottom line: magno is concerned with movement, while parvo is concerned with shape, size and color

Anterior Pitiuitary

aka adenohypophysis Signal reception ∙portal system: parvocellular neurons project from medial HT to a capillary sinus fed from superior hypophysial artery which then travel by vein through infundibulum to anterior pituitary ∙signals are low concentration hormonal signals Neurosecretory type ∙neurosecretory neurons synapse on capillary bed Secretions ∙FSH/LH →triggered by GnRH release to do ova/sperm maturation (FSH) and corpus luteum/ovulation and testosterone support (LH) ∙TSH →TRH triggers →does thyroid hormones (thyroxine, triiodothyronine) ∙ACTH →CRH triggers →does cortisol →CRH also does β-endorphin role in analgesia and sense of well-being ∙GH →GHRH triggers, somatostatin inhibits →causes growth ∙Prolactin →tonic inhibition by dopamine from arcuate nucleus →release inhibition to release prolactin

Posterior Pituitary

aka neurohypophysis Signal Reception ∙magnocellular neurons project from the paraventricular nucleus and the supraoptic nucleus, which project down the infundibiulum and synapse in posterior pituitary Neurosecretory type ∙classic neurons synapse on posterior cells Secretions ∙vasopressin/ADH →osmoreceptors and sensory afferent info to HT →increase H2O reuptake in distal collecting tubule ∙Oxytocin →multiple sources of ascending information →role in lactation, cervical dilation, uterine contractions, complex behaviors like love, bonding, orgasm

Alpha Motor Neurons

alpha motor neurons are lower motor neurons that innervate extrafusal muscle fibers they receive information from many sources simultaneously and have large dendritic trees inputs to an alpha motor neuron include: ∙upper motor neurons from the cortex or brainstem ∙excitatory and inhibitor spinal cord interneurons ∙afferents from muscle spindles inputs are summated within the alpha motor neuron the multiplicity of both excitatory and inhibitory inputs allows for complex integration and modulation of contractile responses if the net result is sufficiently depolarizing to generate an AP, the alpha motor neuron will then emit an End Plate Potential, causing contraction of all muscle fibers it innervates

Targets of Alpha and Gamma Motor Neurons

alpha motor neurons can innervate up to 1000 extramusal muscle fibers using a single axon gamma motor neuron innervate intrafusal muscle fibers

Key Differences b/w Neurosecretory Neurons and Classical Neurons

amount of signal ∙neurosecretory neurons secrete their signal at higher frequency such that although the volume of signal release per event is lower, they total a higher amount of signal secreted receptor affinity ∙neurosecretory hormones have much higher receptor affinity than the affinity for classical neurotransmitters duration of action ∙hormones have a much longer action (hours to week) than NTs (milliseconds)

Olfactory & Gustatory Problems

anosmia = loss of smell hypomia = reduced ability to smell ageusia = loss of taste hypogeusia = reduced ability to taste radiation therapy could kill taste cells and olfactory cilia, or even stem cells that regenerate them head injury could damage the cribriform plate, which could lead to loss of smell losing the ability to taste could lead to problems with getting nutrition ∙if you can't taste, appetite often decreases

Ascending Auditory Pathways

auditory nerves from the two cochlea only interact at the brainstem and the cerebral cortex the auditory nerve travels from the cochlea to the brainstem, and the brainstem nuclei on each side analyze the incoming information ∙auditory nerve fibers synapse on the cells of the cochlear nucleus, which acts as the first processing station the neural signal is passed to the superior olivary complex ∙superior olivary complex also receives input from the contralateral ear ∙b/c it receives contralateral input, the superior olivary complex is involved in sound localization signal then sent to the lateral lemniscus (ventral, inferior and dorsal) and the inferior collculus in the brainstem each stage of this system had many types of neurons to decode the incoming auditory information ∙system is interconnected with parallel pathways carrying unique sets of information ∙information is passed from lateral lemniscus to the primary auditory cortex in the temporal lobe via the medial geniculate nucleus of the thalamus the organization of frequency is maintained throughout the pathway ∙different places in the auditory cortex respond to different frequencies tonotopy is maintained from the cochlea to the auditory cortex

Chronic Stress

bad stress (chronic stress) is classified as experiences where a sense of control and mastery is lacking and which are often prolonger and recurrent, irritating, emotionally draining, physically exhausting or dangerous we are unable/unwilling to act our urges to fight or flee, and this causes stress to become chronic excessive activation of HPA or SNS is deleterious to human health chronic stress does not directly cause, but has been linked to many disease states, such as heart disease, HTN, high cholesterol, T2D, anxiety, paranoia, depression

Static Functions

balance is established by utricle and saccule posture is maintained by vestibulocolic reflexes (VA to motor neurons of neck muscles) and vestibulospinal reflexes (VA to motor neurons in the spinal cord) when stereocilia move towards kinocilia, the trapdoor opens and hair cells depolarize ∙when stereocilia move away from kinocilia, there is a reflexive loosening of the spring, the channel is closed and the hair cell hyperpolarizes the opposite facing organization of utricle and sacucle hair cells on different sides of the striola (indentation) allows for a certain stimulus to evoke depolarization and hyperpolarization, and the curve of the striola facilitates 2D coverage within a plane ∙as we turn our head to the left, the left side discharge frequency decreases and the right side discharge frequency increases ∙our brain interprets head movement from these two signals with different gradation even when we are stationary, our vestibular system is still firing → tonic discharge of CN VIII keeps the system moving, which conserves energy ∙initiating movement is harder than maintain movement the utricle and saccule send afferent fibers that branch to innervate the lateral, medial and descending nuclei of the primary vestibular nucleus ∙the static portion of the vestibular system DOES NOT innervate the superior nucleus ∙in the spinal cord, the medial and lateral vestibulospinal tracts (VST) synapse to innervate motor neurons ∙the lateral VST innervates only the ipsilateral side ∙the medial VST innervates both the ipsilateral and contralateral sides ∙its important to note that the static vestibular pathway travels from the utricle and saccule to CN VIII to either directly innervate the cerebellum or caudal nuclei

Difference b/w Trigeminal System & Olfactory/Gustatory Systems

both olfactory and gustatory systems are very sensitive, in that they only need a tiny bit of an odorant/taste molecule to trigger a response trigeminal system needs a large concentration of irritants

Descending Auditory Pathways

carries signals from the cortex, passes through the brainstem nuclei to the outer hair cells in the cochlea efferent signal from the brainstem directly contacts the base of the outer hair cells stimulation of the efferent nerves to the outer hair cells decreases the sensitivity of the basilar membrane to low sound levels and may help distinguish sounds when background noise is present

Cytoarchitectonics

cell structure of the cortex different cortical regions have different types of cells and functions homotypic cortex: has 6 distinct layers all with similar thickness ∙typical of association cortex (old name for nonsensory/nonmotor) heterotypic cortex: does not have 6 even distinct layers (uneven) and can have 2 types (granular and agranular)

Role of Brain in Stress Response

brain is central mediator of stress response ∙determines what is threatening, as well as subsequent physiological, behavioral, cognitive and emotional response that will be deployed ∙changes in brain plasticity occur in response to stress and can be adaptive (acute stress) or maladaptive (chronic) Hippocampus ∙part of limbic system ∙plays important role in consolidation of new memories, emotional response, storing memories ∙contains cortisol receptors which, when engaged during acute stress enhance cognitive processes, affect mood and motivation, and promote excitability/neuroprotection ∙during chronic stress, hippocampal function is impaired b/c of circulationg glucocorticoids and/or massive SNS activation which leads to shortening of dendrites in CA! and CA3, loss of spines, lower levels of trophic factors, impaired LTP, enhanced LTD, and suppression of neurogenesis ∙these effects lead to impaired memory (explicity, spatial, declarative) and decision making, which makes it more difficult to deal with new challenges and stressors ∙impaired hippocampus leads to inadequate hippocampal regulation of HPA axis, which results in hyperactivation of HPA axis, further potentiating chronic stress Neurogenesis ∙adult process of generating new neuron which integrate into existing circuits after fetal and early postnatal development has ceased which is thought to be an important mechanism underlying plasticity, adaption to environmental changes, and learning and memory throughout life ∙2 neurogenic areas: subgranular zone (SGZ) which is part of dentate gyrus of hippocampus and the subventricular zone (SVZ) which line the later ventricles →neurons of SGZ migrate from dentate gyrus to CA1 and CA3 areas of hippocampus ∙acute stress leads to reversible reduction in neurogenesis in hippocampus ∙chronic controllable stress has no effect on neurogenesis, whereas chronic uncontrollable stress reduces cell proliferation, differentiation and survival or new neurons Amygdala ∙sends impulses to hypothalam for activation of SNS, processing of memory and assigning emotion ∙same stressors may affect the hippocampus and amygdale differently: →dendritic growth and synaptic formation, LTP in the amygdale as well as amygdala dependent cognition are bad ∙hyperactivation of amygdala leads to enhanced fear conditioning and increased anxiety Prefrontal cortex ∙involved in planning complex cognitive behavior, personality expression, decision making and moderating social behavior, orchestration of thoughts/actions, fear extinction ∙PFC has plastic relationship with hippocampus that is needed for flexible memory consolidation ∙within PFC, stress has been associated with dendritic simplification, reduced spine density, disruption of PFC-hippocampal relationship ∙corticosteroids are thought to be responsible for these effects ∙stress-induced changes in PFC lead to diminished cognitive flexibility and decision making

Spatial Hearing

brainstem is where we first build a foundation for spatial hearing spatial hearing utilizes three things to tell where a sound is coming from: time, intensity and phase ∙human hair cells can detect a 7 microsecond delay, and thus a slight time difference will tell us what side the sound came from ∙intensity of the sound is stronger in the ear on the same side as the sound b/c the head deflects some of the sound waves ∙each ear receives sound at different pressure points b/c the sound travels in phasic waves medial superior olivary (MSO) nucleus is used for interaural time differences ∙superior olive receives sound from both sides, but the MSO acts as a co-incidence circuit so that you hear one sound, not the same sound at 2 different times ∙it takes a sound longer to travel to the contralateral MSO than it does to stay on the ipsilateral side ∙brain fires excitatory or inhibitory neurons to control how fast those signals get to the MSO →inhibitory signals are stronger on the shorter pathway of the ipsilateral side, giving the longer pathway more time to send the signal →ratio of inhibitory to excitatory firings depends on distance of sound source lateral superior olivary (LSO) nucleus is used for interaural level differences ∙incoming sound excites LSO neurons on the ipsilateral side (sound from right excites neurons on the right) and activates inhibitory neurons on the contralateral LSO ∙the medial nucleus of the trapezoid body (MNTB) is where the contralateral inhibitory signals cross ∙if excitation from the ipsilateral side is greater than the inhibition from the contralateral side, there is net excitationif the inhibitory signal from the contralateral side is greater, the signal will not continue

Major Motor Loops

called loops because every signal from the motor cortex eventually makes it way back to the motor cortex as feedback we see somatotropic organization, where body parts are regulated in specific structures of the motor cortex one example of a major motor loop is a signal sent from the motor cortex to the spinal cord via a direct pathway called the corticospinal pathway ∙its direct pathway generated in the cortex, ending in the spinal cord ∙no steps b/w ∙spinal cord has motor neurons going to muscles for contraction and movement ∙muscles have sensory receptors that send information back to spinal cord ∙spinal cord shuttles sensory information to thalamus, thalamus sends it back to motor cortex second loop is NOT direct ∙from cortex, signal is sent to brainstem and then to spinal cord ∙from spinal cord, we get movement from motor neurons, sensory information from sensory neurons sent back to spinal cord, then cerebellum, followed by thalamus, and then motor cortex third loop is from cortex to basal ganglia, then to thalamus, and then back to cortex finally, cerebellar pathway ∙information sent from cortex to brainstem, to cerebellum, then back to cortex ∙pathway is very fast and functions to check whether or not a particular movement has been performed

Somatosensory Receptors

can be slowly or rapidly adapting when you think of a receptor that is rapidly adapting, think that it will fire a couple of times and then shut off b/c it doesn't need continuous stimulation ∙slowly adapting pain receptors just keep firing once they become activated (throbbing pain) distinguishing nomenclature w/ DRG neurons and axons ∙Group I is split into two categories: Ia and Ib →division has to do with distinguishing b/w different parts of the intrafusal muscle fibers, aka muscle spindles →Group Ia terminate in annulospiral endings, detect dynamic movement and are primary afferent for intrafusal muscle →Group Ib fibers are the afferent neurons found in the GTO and gives information based on the degree of contraction ∙the two fibers for pain are Aδ and C →Aδ fibers are for fast pain and immediate feedback that comes from touching something hot →C fibers are for slow, dull and inflammatory pain

Animal Studies

can include any procedure done to humans and also many more invasive procedures pros - can do invasive procedures such as single cell recordings cons - findings in animals may not generalize to humans well

Electrophysiology

can measure electrophysiological activity of neurons and activate/deactivate neuronal activity with electrical stimulation Methods: ∙Event Related Potentials (ERP) - electrodes on the scalp measure electrical potentials during an activity ∙Direct Brain Recording and Stimulation - more invasive procedures involves insertion of electrodes directly on the brain to either record or provide electrical stimulation (which can either activate/deactivate fnction) pros - good temporal resolution cons - bad spatial resolution (especially ERP)

Mechanics of the Inner Ear

cochlea has 2.5 windings, like a staircase going up auditory nerve fibers come out of these receptors cells in the basilar membrane there are 3 compartments of the cochlea: the scala vestibuli, scala media, scala tympani the spiral ganglia is the collection of nerves that form the auditory branch of CN8 ∙located b/w the coils of the cochlea in the middle lumen the Organ of Corti is in the scala media, is comprised of hair cells which detect fluid movement ∙organ of Corti is surrounded by endolymph ∙endolymph and perilymph have varying concentrations of K+ (higher K+ in the endolymph), which is essential for the recycling of ions for the continuation of the propagation of APs to the brain ∙endolymph movement increases with the loudness of the sound stimuli there are 3 rows of outer hair cells and one row of inner hair cells ∙only inner hair cells are responsible for hearing ∙hair cells are stuck in the tough gelatinous membrane of the Organ of Corti Cilia of outer hair cells are embedded in the membrane, however, cilia of inner hair cells are not ∙sound stimuli cause deflection, which moves the basilar membrane up and down ∙this pushes and pulls the tectorial membrane, causing the hairs to bend, which results in signal transduction

Columns

columns are a set local highly interconnected cortical neurons that serve as basic processing modules (think all 6 layers connected together by neurons like a stack of pancakes) arise during radial migration of glial cells (neurons will follow them) columns are topographically organized

Forebrain

composed of two components: diencephalon and telecephalon diencephalon is composed of four structures: thalamus, hypothalamus, subthalamus, and epithalamus telencephalon is composed of the: basal ganglia, hippocampus, anygdala and cerebral cortex

Color Vision

cones are what give us color vision only have one type of rod that peaks w/in green wavelength on color spectrum (496nm) but we have 3 types of cones that peak in blue/purple range (419nm), green/yellow range (531nm), and orange range (559nm) when photons of different wavelengths hit our retina, specific cone photoreceptors will respond, allowing our brain to see different colors genes that code for red and green pigment cones are both on the X chromosome, while the blue pigment gene is on an autosomal chromosome ∙b/c these genes are very close to each other, it is easy for there to be crossover or a loss of a gene which results in color blindness

Commissures

corpus callosum = this structure carries most fibers b/w homologous contra-lateral cortex ∙composed of genu = most rostral ∙body = in the middle ∙splenium = looks like a bandage Anterior commissure = those structure carries fibers b/w the homologous contra-lateral amygdalae and anterior temporal cortex

Dynamic Functions

crucial dynamic function is governed by the vestibulo-ocular reflex (VOR) which stabilizes the visual field by producing eye movements compensatory to head movements the VOR acts on extrinsic eye muscles through outputs to CN III, IV, and VI the semicircular canals detect angular acceleration in any spatial dimension ∙each semicircular canal contains a cristae ampullaris, within which is located the cupula (gelatinous material filled with endolymph that encapsulates kinocilia and stereocilia) ∙when we tilt our head, the cupula moves with it but the endolymph stays stationary, which moves hair cells afferent fibers from the horizontal and anterior canals branch to innervate the superior and medial nuclei ∙afferent fibers from the posterior canal branch to innervate all but the lateral nucleus ∙complex connections and integrations exist b/w dynamic vestibular nuclei of the two hemispheres of the brain ∙cortical processing of vestibular information occurs at Areas 2B and 3A, the end result being spatial consciousness

Damage to Motor Neurons

damage to upper motor neurons in the corticospinal tract leads to loss of voluntary muscle movement ∙can result in spasticity (erratic movement) and hypertonia (increased muscle tone) ∙if we lose our voluntary control, we lose inhibition as well as we can see an increased reflex response damage to lower motor neurons also leads to a loss of voluntary muscle movement which can result in hypotonia, muscle atrophy, areflexia (loss of reflexes) and fasiculations or fibrillations (spontaneous twitches) it is also important to remember that where lesions occur affects the side on which symptoms appear due to decussation damage to upper neurons (possibly due to stroke in the internal capsule) results in symptoms appearing contralaterally while damage to the spinal cord will cause symptoms to appear ipsilaterally (b/c fibers crossed in brain stem) ∙damage to lower motor neurons due to lesion in spinal gray matter will also lead to ipsilateral manifestation of symptoms

4 Classes of Sensory Information That Will Be Transmitted

discriminative touch - our ability to tell the different b/w someone touching us at two different locations on our bodies proprioception - perception of oneself, conscious ability to know where our limbs are at all times, even with our eyes closed ∙this ability originates from muscle spindles ∙consumption of alcohol means this is diminished nociception - perception of noxious stimuli temperature (perceived by receptors on skin)

Hypothalamic Disorders

dysfunction of the hypothalamus mainly results from tumors in the hypothalamus or pituitary gland, or external to the system due to spatial relationship w/ the optic nerve, tumors often present with visual deficits adenomas can be secreting if they originate from secretory cells and suppress all other pituitary secretions OR non-secreting if they originate from null cells and still suppress other secretory cells Somatrope tumors result in over secretion of GH ∙if develops before epiphyseal plate closes, results in growth of all bones, including longitudinal growth of long bones, known as Gigantism ∙if develops after epiphyseal plates close, results in growth of all bones but NOT longitudinal growth → everything gets wide, known as acromegaly Hyperadrenalism, Cushing's disease results in centropedal obesity, striae, hyperpigmentation, HTN and emotional liability Hyperthemia - usually from lesions near body temp control areas, surgery, trauma Sexual development abnormalities such as genital dystrophy and precocious puberty feeding behavior abnormalities such as aphagia/emaciation vs hyperphagia/obesity Neurogenic diabetes insipidus (low ADH) HTN - corticotrope tumor, elevated ACTH sham rage - tumors at brain base, impinging on hypothalamus (regulation of amygdala)

Neuron arrangement in V1

each neuron has a preference for a certain orientation, edge, visual space, etc. pinwheels (in orientation maps) tend to be in the center of the occudominance bands and the edges have fairly little orientation change the reason mapping is important is because of what it shows about neural self-organization neural self-organization has to deal with a very big challenge: it needs to represent the original input, which comes in at least 6 dimensions, on a 2-dimensional cortical sheet ∙6 dimensions include RF location (x2), spatial frequency, motion and disparity on top of making sure to cover all dimensions, brain must make sure neighboring neurons respond similarly

Enteric Nervous System

enteric nervous system exists within the entire digestive tract, from mouth to anus is an intrinsic system that helps with digestive processes has 2 sets of plexuses w/in digestive tissues ∙one closest to lumen is the submucosal (Meissner's) plexus, which is located in the submucosal layer ∙the myenteric plexus (Auerbach's) is the au-ter plexus and is located b/w the circular (inner) and longitudinal (outer) layers of muscle intrinsic to the tract, but under SNS and PSNS control ∙PSNS exerts excitatory effects, while SNS exerts inhibitory effects here

Overview of the Vestibular System

essential for maintenance of posture, balance and movement controls the position of our head, as well as compensatory eye movements to stabilize visual field all done without conscious awareness vestibular system is a mechanosensory system composed of hair cells that detect movement ∙each function unit contains 1 tall kinocilium and many shorter stereocilia ∙all hair cells are innervated by vestibular division of CN VIII, the cell bodies of which reside in Scarpa's ganglion ∙hair cells receive efferent innervation from the brain stem, and this is important b/c it allows brain to control afferent signals that it itself receives

External Ear

external ear starts with the pinna (or auricle), which is the external visible portion of the ear the pinna is moveable in certain mammals (not really humans) to amplify sound pinna allows vertical localization to take place as it collects sound sound travels through the external auditory canal to the tympanic membrane (eardrum) ∙vibrating air particles strike the tympanic membrane and provide sound frequencies that the brain must instantly analyze ∙this is unique to sensing sound b/c the sensory stimuli are not continuous, the brain must analyze them immediately

Thalamus

extremely complicated ∙many different nuclei, each with their own inputs and projections anterior thalamic nucleus is mostly discussed in relation to drug abuse, as it receives dense, limbic-related projections the medial thalamic nucleus is located dorsally and medially ∙receives projections from SN and frontal lobe lateral thalamic nucleus contains many neurons that are very important to the motor system ∙organized into dorsal and ventral tiers w/in the lateral thalamic nucleus are the ventral anterior nucleus (VA) and ventral lateral nucleus (VL) which are both part of the motor system, as well as the ventral posterior nucleus (VPL) and ventral posteromedial nucleus (VPM) which help deliver somatosensory information to the cortex the precentral (premotor cortex, BA6) and postcentral gyri (primary motor cortex, BA4) receives projections from the ventral lateral, ventral posterolateral and ventral posteromedial nuclei thalamus is glutamatergic and tonically active ∙if there are lesions in the BG, we will see increased motion b/c we have lost thalamic regulation primary function of the basal ganglia is to integrate and process information ∙help instruct the cerebral cortex via their regulation of the thalamus ∙motor cortex by itself is capable of directing our body's motion, but when we see lesions of BG, we will see jerky and uncoordinated motion

The Direct Pathway of the Basal Ganglia

facilitates flow of movement the MSNs of the caudate and putamen contain D1 receptors, which have an excitatory effect upon these neurons, causing them to produce more GABA when the cortex tells them its ok to start firing ∙this GABA inhibits the high spontaneous rate of firing that we see in the gABAergic SNr and GPi, which in turn decreases the inhiition of the thalamus, allowing it to fire and send its signals back to the cortex ∙this process of increasing thalamic activity and exciting the cortex is called thalamic disinhibition if this pathway stops functioning, the GPI and SNr will just fire away like crazy, the thalamus will never get a chance to signal the cortex, and there will be a net inhibition of motion

Cochlear Implant

functional cochlea and basilar membrane undergo frequency decoding and encoding via fourier analysis ∙deafness often results from non-functional hair cells while the nerve fibers remain functional ∙thus, direct stimulation of the nerve fibers via electrodes along the length of the cochlea can restore perception of sound a single electrode stimulus allows perception of a single frequency impression ∙changing location of the electrode along the length of the cochlea varies the perceived frequency of sound ∙use of multiple electrodes and stimuli locations results in perception of multiple tones ∙implant allows comprehension of speech requires 20-30 electrode contacts along a single integrated wire restoration of hearing works in 2 patient populations: newborns and those who lost their hearing later in life ∙older patients who already obtained ability to perceive speech can easily regain hearing via cochlear implant that bypasses non-functional hair cells with direct stimulation of nerve fibers ∙children born with congenital deafness must have a cochlear implant placed as an infant, with the latest procedures occurring at a maximum age around 2 y/o →if placed too late in development, then the language system is able to develop w/o auditory input and patient loses ability to respond to auditory stimuli via implant →occurs b/c early in language development, the unused auditory cortex is taken over by other sensory inputs cochlear implant uses external microphone connected to a sound processor that processes the signal ∙this processed signal is much more coarse than the intact physiologic system, resulting in decreased resolution ∙requires patient to learn to interpret the crude signal

The Corticospinal Tracts

generated mainly from Brodmann area 4, as well as 6, 1, 2, 3 and some areas of 5, 7 ∙most descending pathways generated from layer V with large pyramidal cells known as Betz cells remember that at the level of the mesencephalon, mid-portion of the crus cerebri will be occupied by corticospinal fibers ∙fibers will be moving through posterior portion of internal capsule ∙area is supplied by important artery that, if broken, can cause ischemia and lead to loss of ability of motor cortex to control muscle movement at level of medulla, corticospinal tract forms pyramids at the level of the intersection b/w medulla and spinal cord, corticospinal tract decussates ∙fibers from the ventral portion of the brain will move to the lateral portion of the spinal cord (lateral corticospinal tract) ∙90% of corticospinal tract crosses laterally and is the lateral corticospinal tract (LCST) controlling limb movement ∙the 10% that does not cross continues anteriorly as the ventral corticospinal tract (VCST) controlling axial/trunk muscles

Gray Matter Organization

gray matter makes up the H structure w/in the spinal cord (even though it looks white in our images, we stain for myelin) can be broken up into dorsal, lateral and ventral horns ∙dorsal horn - contains sensory (afferent) fibers →even though they look like they extend to the edge, they really don't, they just contain poorly myelinated fibers and the indentation known as the dorsolateral fasciculus (DLF) →the wider region as you move toward the center of the spinal cord is known as the substantia gelatinosa ∙Lateral horn - contains visceral fibers ∙ventral horn - contains motor neurons the relative shape of the H structure formed by the gray matter depends on what types of incoming and outgoing fibers exist at that particular level

Vibes

hair cells are organized conotopically such that each hair cell is specialized to respond to a different frequency ∙walking and running cause activation at different frequencies of vibration this is achieved with cilia of different lengths as well as different electrical resonance frequencies, the specificity of which lies in how quickly the hair cell ion channels (mechanosensitive calcium channels and calcium-dependent potassium channels) open & close mechanism by which vestibular system transduces an outside signal (movement) into an electrical signal (AP): ∙cilia movement opens mechanosensitive K+ channels → K+ enters the hair (since endolymph [K+] is very high) cell causing depolarization, which opens voltage-gated Ca2+ channels, leading to the opening of Ca2+-dependent K+ channels, which ultimately allow K+ to escape, repolarizing the hair cell

DCML Pathway

has 3 nerve loops, or three-axon relay ∙we need to know where each nerve's cell body is and where all of the nerves cross over) the dorsal column is made up of the gracile (medial) and cuneate (lateral) fasciculus (first order neuron) the signal for this process originates in the periphery just like any other reflex and is transmitted through pseudounipolar neurons w/ cell bodies in the DRG depending on if the information is being transmitted from the upper or lower half of the body determines which portion of the dorsal column it will travel through ∙sensory information from the lower half of the body is transmitted through the fasciculus gracilis ∙info from the upper half is transmitted by the faciculus cuneatus these neurons synapse on the nuclei of the same name (gracile and cuneate - found in the dorsal medulla) the crossover occurs at the internal arcuate fibers in the pons ∙after they crossover, they keep ascending in the medial lemniscus (Second order neuron, HEAVILY MYELINATED) ∙next synpase occurs at the ventral postereolateral nucleus (VPL) of the thalamus ∙the neurons of the thalamus (third order neuron) then synapse on the post-central gyrus in the sensorimotor cerebral cortex from T6 down, there is only fasciculus garcilis in the dorsal column ∙from T5 up, there are both the cell bodies of the neurons reside in the DRG, not in the nucleus of the same name within the dorsal medulla ∙information in the dorsal columb lines up as it enters into the spinal cord from sacral → lumbar → thoracic → cervical (from medial to lateral) when there is damage to the dorsal columns, symptoms will appear ipsilateral to the affected dorsal column in the dermatome at or below the lesion ∙there will be loss of tactile sense and the person won't be able to describe an object that they hold in their hand ∙they will also have a loss of the sense of position and movement so their movements will be uncoordinated

Pathophysiology of the Basal Ganglia

if there is a lesion of the basal ganglia, there are 3 major disturbances in movement we should expect to see: odd involuntary movement, changes in muscle tone, and abnormal posture hypokinesia can be akinesia (harder to start the motion) or bradykinesia (the motion takes longer to complete and is not as strong as usual) ∙Bradykinesia is seen in Parkinson's patients ∙Hypokinesia results from loss of the D1 direct pathway, leading to tonically active GPi and SNr, inhibiting the thalamus and decreasing cortical activity →D2 pathway is still intact, so there is even more inhibition of the thalamus Several types of hyperkinesia ∙ballismus, or flailing movements of upper arms ∙choreiform movements, which look almost like dance moves ∙atheoid movements, which are continuous writhing motions of the distal portions of the limbs ∙these changes in body's movements can come from enhanced signaling from the D1 direct pathway as well as loss of D2 indirect pathway, all leading to increased activation of thalamus and cerebral cortex Parkinson's is an example of hypokinesia Huntington's, hemiballismus, and Tourette's are examples of hyperkinesia

Depth perception

in the LGN, input for the 2 eyes is segregated from each other however, as we move from layer IV to other layers, we get this blending together of inputs in binocular cells, which sees input from both eyes ∙binocular cells are critical for depth perception if you're fixating on a certain point on one plane (fixation means that point is mapped on the same location on the two retinas), if there is something in front of it (on a closer plane), the brain compares where the new point is mapped on the two retinas to where the fixated point was mapped on the retinas ∙if the object is closer, it is mapped on a different location = disparity we have different cells that are activated when fixating an object and other cells that are activated when there is a disparity ∙zero disparity cell is activated when we fixate on a point ∙binocular disparity neuron is activated when we see an object on a closer/further plane Strabismus is when the eyes cannot be aligned correctly, resulting in depth perception issues ∙want to correct is early b/c there is a critical period for the visual system during which it learns how to do this type of mapping

Tonotopic Organization

information from the cochlea is preserved all the way to the cochlea nucleus there are many different cell types within the cochlear nucleus, but all of those cells receive terminals from the same auditory nerve axon different areas of the cochlea nuclei are designed to react to different frequencies and intensities, therefore, the frequency of the tone dictates which neurons fire ∙frequency tuning allows for fine-tuned hearing, as frequency analysis is how we hear tone ∙as frequency increases, the amount of excitation decreases, and the amount of inhibition increases the basilar membrane in the cochlea is tonotopically organized, meaning that different frequencies affect the specific regions along the length of the membrane ∙the unique response of the basilar membrane to unique frequencies is maintained throughout the signaling pathway ∙varying hair cilia length along the length of the basilar membrane make his possible high frequency sounds are detected near the base (near the oval window) of the cochlea ∙recognized by the posterior part of the cochlear nucleus before being sent to the ventral superior olivary nucleus low frequency sounds are detected near the apex (helicotrema) of the cochlea ∙recognized by the anterior part of the cochlear nucleus before being sent to the dorsal superior olivary nucleus

Inner Ear

inner ear is the temporal bone of the skull has 3 parts: ∙the front part is the snail shaped cochlea, which functions in hearing ∙the rear part is the semicircular canals, which function in balance ∙the vestibule connects the cochlea and canals, and has the sensory organs responsible for balance if we uncoiled the cochlea, there is a basilar membrane that runs in the center of the lumen and is surrounded by perilymph ∙the perilymph fluid is called the scala vestibuli on the side of the semicircular canal, and the scala tympani on the tympanic membrane sound sounds enter the cochlea and are transferred to the basilar membrane ∙different areas of the basilar membrane vibrate to different frequencies ∙towards the apex (semicircular canals), the membrane responds to low frequencies ∙towards the origin (by the windows), the membrane responds to high frequencies Fourier transform is how the cochlea separates complex waveforms or sounds into a single, simple frequency

Internal Capsule

internal capsule is a major axonal pathway to and from the cerebral cortex, thalamus, basal ganglia, brainstem and spinal cord passes through and separates the neostriatum (basal ganglia) into the caudate nucleus and putamen composed of 3 parts: ∙anterior limb = located in the front, it serves to separate the caudate and putamen ∙genu = located near the anterior nucleus of thalamus "genu" means bend so look for the bend on any diagram and its most likely the genu ∙posterior limb = located behind, serves to separate the lentiform nuclei from the thalamus

Methods for localizing cortical function

lesion studies functional neuroimaging: PET, fMRI electrophysiology: ERP, direct brain recording and stimulation magnetoencephalography: MEG transcranial magnetic stimulation: TMS animal studies

Topographic Organization of Motor Neurons

like the cortex, the spinal cord has a topographic organization medial fibers will correlate to medial muscles whereas lateral fibers will correspond to more distal muscles additionally, fibers innervating flexors will appear more dorsally while fibers for extensors will appear more ventrally

Similarities b/w Trimigeminal System & Gustatory System

like the gustatory system, the trigeminal system's axons project to the VPM nucleus of the thalamus

Lesion Studies

limited lesion which leads to a limited deficit in function suggests that the function which has become impaired is localized to that region of the brain these legions that can be readily studied are focal lesions found often in patients with stroke or traumatic brain injury (TBI) or neurodegenerative diseases (before they become too diffuse) Pros: lesions can strike particular brain structures and be useful for study Cons: lesions can often be large and cover many structures, due to brain plasticity the brain can adapt after a lesion to regain function making inference of brain function difficult

Middle Ear

middle ear is an air-filled chamber internal to the tympanic membrane and external to the oval window of the cochlea middle ear connects to the throat/nasopharynx by the Eustachian tube, which functions to equalize air pressure on both sides of the eardrum the middle ear is susceptible to ear infections (otis media) b/c bacteria can travel up the Eustachian tube to the middle ear from the nasal cavity three linked, moveable bones (ossicles) adjoin the eardrum to convert sound waves striking the eardrum in mechanical vibrations ∙the bones (external to internal): malleus → incus → stapes ∙malleus is on the inside of the eardrum and acts as a hammer ∙the incus is the middle bone and acts as an anvil, connects the malleus to the stapes ∙the stapes is the "stirrup" the base of the stapes fills the oval window, a thin membrane leading to the inner ear function of the middle ear is impedance matching, or the transfer of acoustic energy from compression waves in air to fluid-membrane waves in the cochlea ∙amplifies the small vibrations from low impedance large area of the eardrum to the smaller, high impedance oval window of the cochlea middle ear transforms incoming low-pressure, high displacement vibrations into high-pressure, low displacement vibrations in order to drive cochlear fluid as the eardrum vibrates, the bones move like a seesaw and the stapes hits the oval window of the cochlea to amplify the sound and move the cochlea fluid ∙b/c the cochlea is a closed compartment, it needs a round window on the other side to bulge in response to added pressure ∙pressure is amplified in cochlea b/c of the smaller area of the oval window and the force from the stapes

Ganglion cells

most anterior layer of retina send signal to the optic nerve cells are the first spiking cells, meaning that they convey the signal from analog (graded response) to digital (spiking response) 2 types of ganglion cells: on-center and off-center ∙on center cells respond the best to light against dark background, while off-center cells respond best to dark against a light background ∙these cells don't respond to light, but rather to contrast and edges Why do these cells respond to a center-surround? ∙reason is there are 100 million photoreceptors, and only 1 million fibers in optic nerve ∙ganglion cells are faced w/ task of recoding and compressing the info that comes through retina before sending it to the optic nerve ∙are able to do this b/c in nature, vision is very redundant and predictable with temporal and spatial correlations → means that pixels that are close in space and time are very similar, use this by de-emphasizing the redundancy such as areas with constant illumination, while emphasizing areas of edges or of areas w/ contrasts

Motor Control

motor cortex is involved in planning, initiating and directing voluntary movements ∙movement supervised by motor cortex is improved with practice brainstem (formed by medulla, pons and mesencephalon) is capable of generating basic movements and postural control ∙brainstem centers are responsible for reflex responses ∙reflexes have developed through evolution in the spiral cord, we have circuits for muscle contraction and movement through interneurons (used for reflex coordination) and motor neurons the motor neurons of the descending systems can be divided into upper motor neurons in the motor cortex and brainstem, and lower motor neurons in the spinal cord

Motor Neurons

motor neurons carry motor signals their relative proportion within the spinal cord varies w/ segmental level (limb regions will have more motor neurons than the thoracic region) they are arranged as elongated nuclei, and four our purposes are classified by where they are in the nervous system (lower vs. upper) and what they innervate (alpha vs. gamma)

Pain modulation

multiple ways to modulate pain sensitivity hyperalgesia - increase in response to noxious stimuli, spontaneous pain allodynia - perceive innocusous stimuli as pain (i.e. sunburn) analgesia - decrease or block in response to noxious stimuli without affecting other somatosensory stimuli (specific to pain) anesthesia - decrease/block to all somatosensory stimuli (blocks all somatosensory and motor neurons) spinal cord is involved in modulation of pain ∙primary afferents come into the spinal cord and synapse in the dorsal horn ∙these synapses are glutamatergic and release glutamate ∙upon release of glutamate you get a form of LTP in the spinal cord called central sensitization of transmission ∙if you receive a barrage of activity you can upregulate the receptors and aget a form of LTP that can cause more pain touch is also a key factor in pain modulation ∙we have reflexive touch behaviors in response to pain ∙for example, if you hit thumb w/ hammer, you wave hand around which causes vibratory stimulus that engages all of our touch receptors called the gate control theory of pain ∙based on the hypothesis that if you engage all the receptors than there is a huge barrage of activity at the spinal cord so there is less room for pain to come in ∙we now know that touch receptors do not synapse in the spinal cord but go directly to the brain stem, where they give over collaterals, some of which can be interneurons that travel to spinal cord and inhibit pain fibers opioids are very powerful analgesics, and they work by inhibiting C fibers b/c C fibers are loaded with opioid receptors ∙do not work well at Aδ fibers therefore when you use opioids you can still feel fast pain, but not slow pain

Muscle Spindles

muscle spindles are essentially clusters of both extrafusal and intrafusal muscle fibers and are used to provide sensory information about proprioception to help the muscles perform coordinated and precise movements extrafusal muscle fibers are those associated with the contraction and are innervated by the alpha motor neurons ∙intrafusal muscle fibers are innervated by gamma motor neurons and provide sensory feedback information about the length of muscles ∙these are important to muscle spindle function basically, the spindles are part of a reflex mechanism that allows us to coordinate movements ∙while alpha motor neurons initiate contraction in one set of extrafusal muscle fibers, they are inhibited in the counteracting muscles and allow them to go slack ∙we have innervation of our intrafusal muscle fibers by gamma motor neurons which help hold tension in the relaxed muscle → these detect the amount of stretch in the relaxed muscle fibers and provide information about where our muscles are in space →this signal comes back to spinal cord and brain and helps us coordinate smooth, controlled movements

Neocortex Characteristics

neocortex surrounds the cerebrum it is 2-4 mm thick (visible to the eye) and covers area of about newspaper page highly folded allowing it to have more processing power and speed can be broken down into 6 laminar layers and columns has distinct connectivity and cytoarchitectonics (cell structure of the cortex) depending on its location in the cerebrum ∙this suggests that they have different functions due to this variability functions: all vary by region but include sensory, motor, cognitive, social and emotional

Studies on Nonhuman Primates

nonhuman primates have similar brains to humans, provide the best model of human brain for study sound stimuli and corresponding brain activity can be coarsely visualized with PET, which shows activity in the suoerior temporal cortex, inferior parietal cortex, and frontal cortex towards Brocha's area (speech production) ∙this wide area of activity in response to sound stimuli suggests interconnectivity single unit studies using animal models have been able to precisely localize the primary auditory cortex deep within the lateral sulcus surface recording in the secondary auditory cortex led to the mapping of the lateral belt area, which showed the same tonal-topical gradient as observed in the primary auditory complex ∙thus we see a map of the basilar membrane frequency distribution in both the primary and secondary auditory cortices staining techniques have been able to localize and differentiate the dark staining primary auditory complex from the light staining lateral belt currently 20-25 auditory areas of the brain, each with preserved tonal-topical organization ∙more peripheral areas are less organized with mixed frequencies reflecting processing of complex sounds using labeled tracers that are transported along nerve fibers, connections b/w superior temporal cortex and frontal cortex were observed, originating directly from belt areas ∙tracer administration to the antero-lateral (AL) belt showed projection to ventral locations in the frontal cortex, while the caudal-lateral belt (CL) projected to dorsal locations in the frontal cortex ∙projections to segregated zones in the frontal cortex are thought to have the same function as their lateral belt area originations ∙projections to the auditory cortex occur from the medial geniculus of the thalamus ∙ventral division of the medial geniculus projects to the main auditory areas while the dorsal division of the medial geniculate projects to caudal belt areas Recordings from the belt areas show that the AL region shows activity in response to communication calls, as opposed to the CL region, which responds to sound localization, spatial position, etc ∙this is the dual stream model with the dorsal "Where" stream and the ventral "what" stream, similar to the visual pattern of projectivity ∙located dorsally to auditory areas, the parietal lobe is involved in spatial sound localization ("where"), with projections to the dorsal lateral prefrontal cortex (DLPFC), the site of working memory for location ∙located ventrally to auditory areas, the temporal lobe is involved in object identification ("what") in both the visual and auditory systems, with projections to the ventral lateral prefrontal cortex (VLPFC) ∙single unit recordings in nonhuman primate brains and surface EEG recordings in human brains show that the dorsal ventral streams eventually converge within the frontal cortex, with projections back to the auditory cortex as well dorsal stream can be visualized (PET) with posterior secondary auditory cortex activation during sound stimuli of auditory space (especially motion of sound in space), with activation extending into the inferior parietal cortex ∙ventral stream can be visualized (PET) with anterior superior temporal cortex activation during sound stimuli of auditory objects (e.g. speech sounds, individual voices) ∙imaging during auditory space and object stimuli show activation of dorsal localization areas during space stimuli and activation of ventral recognition areas during object stimuli

Trigeminal System

noxious stimuli (could be anything like acetic acid, ethanol, ammonia, etc.) will be detected by chemoreceptors on nociceptive (pain) neurons in the face, scalp, cornea and oral/nasal cavities once an irritant binds to the receptors, the signal is transmitted to CN V (trigeminal), IX (glossopharyngeal), and X (vagus) ∙trigeminal nerve contains 3 sensory branches: ophthalmic nerve, maxillary nerve, and mandibular nerve

Olfactory Pathways

odors come in the nasal cavity airborne odors will bind to the receptors on the olfactory neurons these neurons will travel in the olfactory nerve (aka CN I) and go through the cribriform plate to synapse in the olfactory bulb the olfactory bulb will project via the olfactory tract to areas in the ventral (bottom) part of brain: ∙pyriform cortex, olfactory tubercle, amygdala, and the entorhinal cortex from here, neurons will project to the orbitofrontal cortex, thalamus, hypothalamus, and hippocampal formation

Receptor Binding and Mechanism of Detecting Smells

olfactory receptors are only olfactory neurons, not the olfactory epithelium ∙receptors are on the cilia of the dendrite keep in mind that this first sensory neuron is unmyelinated and bipolar ∙one branch extends out into the nasal cavity while the other branch extends away from this toward the olfactory nerve once the odorant binds the receptor, it activates a G-protein coupled receptor that leads to the formation of cAMP ∙cAMP will open Na+/Ca2+ symport that brings both cations into cell ∙sodium will depolarize cell, while calcium is used as a co-agonist to the chloride efflux channel, which will further depolarize the cell ∙this depolarization will generate an AP in the cilia that will be transmitted to the olfactory bulb How does adaptation work? ∙there are a couple of mechanisms in play here that work to prevent depolarization and thus the transmission of the AP ∙CAM (calmodulin) can bind calcium and prevent it from binding to the chloride channel ∙there is a Na+/Ca2+ antiport that will remove calcium from cell ∙cAMP can be degraded so it doesn't activate symport

Other Players in the Olfactory Sensory System

one of the most important accessory cells is the Bowman's gland, which secretes mucous into the nasal cavity ∙if there wasn't a mucous layer, any toxic odorants that got into the nasal cavity would bind directly to the receptor and kill it ∙mucus serves protective function and odorants must first dissolve in the mucus before they are detected ∙despite this protection, some cilia and receptor will inevitably be damaged/killed and need to be replaced by stem cells in the area each of the sensory neurons will display just ONE type of receptor, although there could be many copies of a neuron expressing a particular receptor throughout the entire olfactory system ∙olfactory bulb is organized into units called glomeruli, and all the neurons that express the same receptor will send their axon projections to a designated glomerulus ∙in the glomerulus, there will be another set of neurons called mitral cells and tufted cells that will gather information, amplify the signal, and finally leave the glomeruli through the olfactory tract olfactory system is similar to auditory system in that pleasant odors are grouped together in close proximity to areas associated w/ other pleasant odors ∙same goes for unpleasant odors

The Ear

outer ear is just for spatial hearing hearing happens in the inner ear → more specifically in the brainstem ∙congenital deafness (present at birth) is a problem with the inner ear cochlea is the snail like structure that is the auditory portion of the inner ear ∙cochlear nerve carries sound information from cochlea to the cochlear nuclei, which are collections of neurons in the mammalian brainstem ∙cochlear nucleus is the first place in the brainstem where electrical signals are produced inferior colliculi are the main hearing parts of the brainstem ∙located just below the visual processing centers (superior colliculi) and are the first place where vertically orienting data from the cochlear nuclei can synapse with horizontally orientating data ∙this is essential for sound location data medial geniculate nuclei of the thalamus send the signals to the primary auditory cortex to be processed

Pain Afferent Pathways

pain and temperature afferents travel via the anterolateral-spinothalamic tract enter the dorsal horn and immediately synapse ∙this synapse is key b/c it allows for modulation of the signal in contrast to touch which is fairly conserved, pain is labile b/c there can be modulation at this synapse ∙signal then crosses over to contralateral side and is carried to the thalamus and then somatosensory cortex afferents from the cranial nerves travel via the trigeminal system, where they enter at the brainstem, cross over and go to the thalamus, and then the somatosensory cortex

Pain Fibers

pain and temperature sensations are carried by Aδ and C fibers (also called nociceptors) these fibers are lightly myelinated (A delta) or unmyelinated (C fiber), have medium and small diameters, and carry polymodal pain stimulation and temperature slower conduction speed → ~0.5-30m.sec have bare nerve endings that are often highly fenestrative

Pain

pain is a perception very labile has an effective component unlike other sensations type of pain perceived depends on activities of pain fibers Aδ fiber responds to acute danger, such as standing on nail/touching stove ∙response is fast to avoid danger C fiber makes up 80% of fibers ∙cover entire body, most prevalent fiber in skin (more than touch fibers) ∙involved in classic inflammatory pain ∙respond to acute inflammation and their purpose is to induce prolonger sensitivity that allows for repair another type of pain is neuropathic pain ∙arises from traumatic damage to neurons ∙can result from virus that infects the nerve

Monosynaptic Stretch Reflex

pathway: stimulation of the neuromuscular spindle travels through the primary sensory neurons in the DRG and makes a single excitatory synapse on an alpha-motor neuron ∙there will then be firing of the alpha-motor neuron on the extrafusal muscle fibers of the homonymous (same) muscle upon stimulation of the muscle, an inhibitory interneuron is also stimulated that sends an inhibitory stimulus to the antagonist muscle via its alpha motor neuron in addition to the activation of the alpha motor neurons, the co-actiation of the gamma-motor neurons is essential to maintain the tautness in the intrafusal muscle fibers ∙creates constant feedback even during extrafusal muscle contraction

Photoreceptors on a molecular level

photoreceptors depolarize to dark and hyperpolarize to light in the dark, there are high cGMP levels inside the outer segment of the rod ∙cGMP binds to the Na+ channels, allowing them to stay open and depolarize in presence of light, photons hit the rods and there is phototransduction causing cGMP levels to drop ∙w/o high levels of cGMP, Na+ channels will close leading to hyperpolarization distribution of rods and cones in eye is not homogenous throughout retina ∙fovea contains highest cone density ∙foveola has only cones →area w/in fovea, w/ visual angle of 1.5° →part of eye w/ highest visual acuity ∙optic disk contains no photoreceptors, is why we have a blind spot

Positive-Negative Signs After Lesion of CST

positive sign - acquiring a function that is normally there ∙nBabinksi sign (abnormal) is where there is extensor plantar response or dorsiflexion of large toe, with the rest of toes fanning out ∙used clinically to find lesions in corticospinal tract Negative sign - loss of function (paralysis) pathways from brainstem are important for control of posture ∙problems in brainstem can alter posture ∙with brainstem injury, we can see decerebrate posture with upper and lower limbs extended or decorticate posture with upper limbs flexed and lower limbs extended

Motor System Hierarchy

posterior parietal, PMA and SMA cortices at the top send info to the primary motor cortex from here, primary motor cortex interacts w/ other parts of brain to issue commands once command is fulfilled you have input from sensory system going back to primary cortex to approve/disapprove of movement, learn from movement, and/or refine it basal ganglia and cerebellum can also be involved to support primary motor cortex's direction and planning of movement if you remove portion of posterior parietal/PMA/SMA cortex, you would still be able to move, but would lose complex movements w/ multiple muscles/joints

Tinnitus

ringing sensation of various presentations that effects millions, especially veterans can be debilitating if severe, often associated with depression and suicide loss of hair cells due to loud noise exposure (120+dB) can result in hearing loss and tinnitus ∙however, only 30% of hearing loss patients experience tinnitus cutting of the auditory nerve has also been observed to result in tinnitus tinnitus originates in the brain, resulting from reorganization of the auditory cortex, an example of lesion induced plasticity ∙comparable to phantom pain/limb, resulting from reorganization of somatosensory system following amputation/damage in which remaining neuronal connections continue to fire high frequency hearing loss is a normal part of aging past 40-45, possible resulting when base of basilar membrane of cochlea wears out ∙distinct from tinnitus patients who show advanced high frequency hearing loss starting at lower frequencies or notch-like hearing loss ∙a cochlear lesion resulting in no input of the auditory cortex allows neighboring frequencies to expand into vacant cortical region, resulting in overrepresentation of border edge frequencies ∙additionally, tinnitus patients show auditory complex hyperactivity frontal cortex includes a secondary process that reduces noise in a top-down manner ∙region has been found to be damaged in tinnitus patients ∙location is associated with dissonant/unpleasant sounds, with projections into the limbic system that controls emotional reactions/processing ∙this non-auditory system receives auditory signals and is able to compensate for any tinnitus present ∙patients with persistent tinnitus are unable to suppress the signal 3 causes of tinnitus (all 3 have to be present) are peripheral hearing loss, central auditory reorganization, and lack of top-down (limbic) suppression) ∙may be genetic predispositions for loss of suppression

Major Descending Pathways

rubrospinal pathway arises in the red nucleus (large nucleus in mesencephalon), reaches spinal cord ∙involved in voluntary limb muscle movement ∙this tract crosses over at the level of the spinal cord and is located very close to the lateral corticospinal tract ∙if you were to lose LCST, you would use this tract to perform all the same movements, except for fingers reticulospinal pathway is a pathway from reticular formation down to spinal cord ∙allows us to move flexors and extensors ∙lesions here can cause rigidity in the muscles when flexors and extensors are not properly coordinated in their activation vestibulospinal pathway is from vestibular nucleus down to spinal cord ∙allows us to stand against gravity and balance, even with head movement tectospinal tract will move from superior colliculus to spinal cord ∙coordinates neck movement with eye movement

Itch

select group of C fibers code for itch itch sensation is both histamine dependent and independent aiding in itch sensation is a secondary afferent that contains a gastrin releasing peptide receptor (GRPR) that is an itch specific gene in the spinal cord itch is thought to be a submodality of pain one of the side effects of opioids is prominent itch b/c you knock out all the pain so you actually feel itch

Temperature

sense temperature through transient receptor potential (TRP) channels 27 of these ion channels in humans ∙about 6 or 7 are involved in temperature system TRP is an excitatory channel and the TRP gene codes for an ion channel that admits sodium and calcium into cell we have an exquisite sense of temperature because we have a large combination of TRP receptors with different temperature set points TRP channels that aid in temperature regulation ∙TRPV1 - capsaicin, heat (>43°C), H+, lipids (sensory nerves) ∙TRPV2 - heat (>50°C) (sensory nerves, brain) ∙TRPV3 - innocuous heat (>35-39°C) (skin, brain) ∙TRPV4 - hypotonic (stretch, >28-36°C) (skin, brain, lung, kidneys) (activated in normal thermal body range) ∙TRPM8 - cold (<25°C), menthol (sensory nerves, prostate, colon cancer) ∙TRPA1 - cold (<18°C), mustard oil, wasabi (Sensory nerves, co-expressed with TRPV1) about 5-10% of C fibers code for temperature and send information to somatosensory cortex TRPV1 agonist induce hypothermia and TRPV1 antagonists induce hyperthermia

Sensory Fibers

sensory neuron cell bodies reside in the dorsal root ganglion ∙projecting from the cell body are small axons that branch into 2, and these are called the pseudounipolar axons ∙on the end that extends away from the spinal cord will be our sensory receptors →when they are stimulated, the impulse will run past the cell body and into the gray matter of the spinal cord and is able to communicate directly or indirectly (via interneuron) with the alpha motor neuron ∙within the dorsal horn you can find collateral branches, which make up ascending pathways remember that efferent fibers enter and afferent fibers travel away from the spinal cord spinal nerves make up such discrete demarcations of innervation throughout the body you can map their projections to the skin through the dermatome map ∙a sensory dermatome is an area of skin innervated by nerve fibers comprising a single dorsal root ∙face is supplied by cranial nerves

The neurons in V1

simple cells respond to edges (i.e. a bar stimulus) ∙these cells also care about the orientation of the edge (i.e. whether the bar is vertical, horizontal, slanted, etc.) ∙edges are a great description of objects and allow for what is know as a sparse code → rather than having the activation of the retina, photoreceptors and other things, you have a strong activation of a relatively small amount of neurons ∙as long as we have cells that can notice edges, we can have less activation, but still have enough input to make something meaningful of it the function of V1 is to recode information in a way that makes it more meaningful there are simple and complex cells in V1 ∙both respond to oriented bars/edges ∙Simple cells have a small receptive field and are the first step in the brain where edges are distinguished ∙complex cells have bigger receptive fields and translation tolerance → respond to edges in different positions Simple cells, while responding to very specific edges, all provide input to a complex cell

Somatosensory System

somatosensory system receives information on multiple types of sensation from the body sensations include: light, touch, pressure, joint and muscle position sense (proprioception), pain, temperature, itch (sensation that triggers desire to scratch), and prickle (does not trigger a scratch response, just considered to be noxious) previously it was thought that these somatosensory sensations were all carried by one type of sensory neuron that carried information to the cortex ∙through variations in firing frequency the cortex was then able to interpret the different sensations now it is thought that these stimuli are all carried by separate fibers, and each system is separate 2 major anatomical groups of afferent sensory fibers in the somatosensory system ∙first group is the afferent nerves that come into the spinal cord from all the dermatomes of the body →enter via the dorsal root ganglia, which are arranged all along the vertebral column →dorsal root ganglia contain all the cell bodies of sensory afferent nerves from the periphery (nerve endings themselves are very small and hard to study so what researchers typically do is isolate the ganglia and break them up into individual cells bodies, in doing so all receptors that are normally trafficked on nerve endings are contained in the cell bodies and can be studied with electrophysiology) →the signal from the cell bodies then continues into the spinal cord and goes up to the brainstem ∙second major group of sensory fibers is the cranial nerves →come into the trigeminal ganglia at the brainstem there is also a third group of visceral vagal afferents that come from the brainstem from nodos ganglia ∙these afferents are more internal than somatosensory

Spectrogram

spectrograms are descriptions of complex sounds that represent vocal cord vibrations as sound frequency variations over time, with strong harmonic tones occurring at vowels characteristic frequency changes are called formants ∙two formants form resonances in the vocal apparatus, with phonemes characterized by apparatus production method ∙thus, spectrograms are tuned to properties that the motor system initially used to produce the sounds (i.e. the mechanical properties of sound production are encoded in spectrograms) speech sounds show characteristic frequency distribution, harmonicity, timing, and changes over time frequency chances can be exemplified via sweeps, with variation in speed, direction, etc ∙different neurons in the auditory cortex respond differently to different sweeps ∙neurons exist that are tuned to various properties of speech sounds ∙these neuronal activities summate, allowing imaging of overall activity in the primary auditory cortex and superior temporal cortex ∙speech recognition is fairly selective, with different areas of the brain activation with different syllable stimuli →syllables stimulate anterior regions of the superior temporal cortex into the VLPFC in both humans and nonhuman primates (ventral "what" pathway) vowel stimuli shows distinct areas of activation compared to noise, with activity in the anterior superior temporal cortex into the inferior frontal cortex ∙there is no observed activation in reponse to language within the classical region of language recognition, Wernicke's area ∙meta-analysis has showed consensus that a new word recognition site exists anterior to the classical location of Wernicke's area ∙imaging has shown that phonemes and verb stimuli result in anterior activation rather than posterior activation (location of Wernicke's area)

Sound Speech Extraction

speech-sound extraction involves the mechanisms for complex perception it has been known that the auditory cortex is responsible for sound decoding while another center is responsible for producing sound this requires connectivity, and the exact locations and layout of communication have been studied speech decoding occurs in Wernicke's area, with projections to Broca's area via the arcuate fasciculus Broca's area is responsible for speech production, with projections to the motor cortex for vocal apparatus (vocal cords, tongue, etc.) movements other routes of connectivity exist in addition to this classical model

Spinal Segments

spinal cord can be broken up longitudinally into distinct spinal segments by following roots and rootlets of the spinal nerve back to the spinal cord these segments are very important for sensory applications, particularly the spinal segment reflex circuit, in which sensory neurons enter the spinal cord via the dorsal root and: ∙synapse on motor neurons to trigger a reflex ∙modulate reflexes by synapsing on interneurons ∙ascend the spinal cord to the brain to provide sensory feedback humans have 31 spinal nerves ∙starting from brainstem and moving caudally, we have 8 cervical, 12 thoracic, 5 lumbar, 5 sacral and 1 coccygeal spinal nerves it is important to note that the spinal cord ends at approximately L2/L3 at the conus medullaris ∙the remaining spinal nerve rootlets will continue to descend making up the cauda equina before exiting at their corresponding vertebral levels the pia mater will make up the filum terminale internum, which continues down the vertebral column, exits the dura to become the filum terminale externum, and finally attaches the spinal cord distally to the coccyx ∙dura will also continue to descend with the rootlets and contain CSF ∙this organization allows us to perform a lumbar puncture to sample CSF w/o damaging the spinal cord ∙the individual spinal nerve rootlets are free to move and evade puncture by incoming needle, and in the case that they are hit, they are made up of neurons that can regenerate if damaged

Spinal Nerves

spinal nerves are peripheral nervous system projections that carry neurons from the spinal cord to their prospective targets contain both afferent (dorsal) and efferent (ventral) fibers and carry motor, sensory and autonomic signals neurons that carry sensory information form rootlets that enter the spinal cord dorsally ∙these neurons are considered pseudounipolar and their cell bodies are found within the dorsal root ganglion the ventral fibers contain efferent neurons (primarily motor) which form rootlets and meet up (but do not interact) with the afferent dorsal root fibers at the dorsal root ganglion to form the spinal nerve Recap: ∙Spinal nerve = afferent + efferent fibers ∙Dorsal root = afferent, sensory ∙Ventral root = afferent, motor

Spinal Cord Reflexes

spinal reflex is an involuntary and instantaneous rxn to stimuli reflex arcs are mediated through the spinal cord and do not require brain involvement ∙they are created by firing of an efferent motor neuron in response to stimulation by an afferent sensory neuron important reflexes are stretch, flexion and crossed extension if the extrafusal muscles (alpha-motor) are stretched, then the intrafusal gamma-neurons) muscle spindle afferents are stimulated b/c they run in parallel ∙this will cause firing of the Group I and II afferents

Beginning of Vision

starts in the eye with light traveling through the pupil and projecting to the back of the retina important structures: sclera, pupil, iris, retina, optic disk, macula, and fovea ∙sclera is the protective white outer covering of eye ∙pupil is where light enters the eye ∙iris is colored part of eye that controls the diameter and thus how much light enters the eye ∙optic disk is located in retina and is where optic nerve leaves the eye →where our blind spot is as light passes through the cornea and lens, it will be refracted ∙thickness of the lens will affect the amount of refraction to allow for the image to focus on the back of the retina ∙this process is called accommodation and is governed by the ciliary muscles ∙the innate shape of the lens is a ball so when the ciliary muscles contract, and the zonule fibers relax, it will flatten the lens out to allow for less refraction at a distance ∙for images nearby, the ciliary muscles will relax while the zonule fibers contract to allow for more refraction after light passes through the lens, it will pass through the inner chamber of the eye and project to the retina in the posterior wall of eye ∙macula is a highly pigmented area of retina ∙fovea is point of eye w/ highest density of photoreceptors, where we have highest visual acuity in the retina, there are several layers of cells that light has to pass through in order for the image to be transduced ∙we focus on photoreceptors (rods and cones) and ganglion cells

Functions of Motor Cortex Areas

supplementary motor area (SMA) - plays role in programming of complex sequence of movements and gives rise to bilateral movements coordinated on 2 sides of body Premotor Area (PMA) - when stimulated, we evoke complex movement involving multiple joints and resembling natural coordinated hand shaping or reaching movements Brodmann areas 5 & 7 are able to send information to PMA ∙integration of sensory odalities from areas 5 & 7 are important for: ∙transforming visual info about the properties of objects ∙transforming visual info about the location of objects Proprioceptive input from muscles (S1) and integration of auditory and visual sensory modalities (areas 5 and 7) will send info to PMA< which will eventually send info to primary motor cortex Primary Motor Cortex (Brodmann area 4) functions in execution of voluntary movements ∙influences the force of a given muscle and the extent of movement ∙specificity direction of reach ∙controls speed of movement

Gustatory Pathway

taste is transmitted through CN VII (facial - anterior 2/3 of tongue), IX (glossopharyngeal - posterior 1/3), and X (vagus - epiglottis) from here, neurons converge to solitary nucleus of the brainstem, forming the first synapse another set of neurons will be sent to the ventral posterior medial (VPM) nucleus of the thalamus, which acts as relay center for sensation finally, neurons in the thalamus will project to the cortex in 2 locations: insula and frontal operculum NOTE: gustatory system relays info to the thalamus ∙olfactory system does NOT → instead, olfactory neurons went up to the cortex and skipped the thalamus

Terminals of Dorsal Root Ganglion Neurons

terminals of DRG neurons form free nerve endings or innervate encapsulated receptors the encapsulated type is more common and is generally of larger diameter, myelinated, and faster conducting in comparison, the non-encapsulated receptor is thin, unmyelinated/lightly myelinated, and slow conducting

Globus Pallidus

the GP is medial to the putamen, with a tract of white matter in between the internal and external nuclei it contains GABAergic neuron that are spontaneously active ∙important if there is a lesion on the striatum → tonic inhibition of its targets the main input comes from the striatal complex, feeding the GPe GABA and enkephalin and the GPi GABA and substance P ∙GPi is part of the direct pathway and projects to the thalamus via pallidothalamic fibers ∙GPe is part of the indirect pathway and projects to the STN via pallidosubthalamic fibers and is connected with the SN via pallidonigral fibers

The Ventral Stream

the HMAX model of object recognition in the cortex reflects the understanding of how processing goes from simple cells to complex cells to simple cells to complex cells over and over again until the projections move from V1 to the anterior inferotemporal cortex (AIT) to the prefrontal cortex (PFC) the power of the brain comes from hierarchy there are only 2 operations that must take place to get object recognition ∙detect edges as input goes from LGN → simple cells ∙increase in invariance (i.e. scale and lighting changes) as input goes from simple → complex

Substantia Nigra

the SNr and GPi are the output nucleu of the basal ganglia (final step in both the indirect and direct pathways leading to feedback to thalamus) the SN is part of the midbrain and can be divided into pars compacta (SNc) and pars reticulata (SNr) ∙SNc is the source of motor system's dopamine, while SNr is GABAergic SNr neurons are tonically active and projects to superior colliculus, thalamus and pontine reticular formation SNc project to caudate and putamen nuclei ∙get knocked out in Parkinson's disease histologically, when you do an H&E stain (selects for proteins and nucleic acids) of the SN, the SNc cell bodies show up as brown from the melanin that is a byproduct of dopamine synthesis ∙even without staining, the SN is much darker than surrounding tissue

Featured units in object recognition

the anterior inferotemporal cortex (AIT) is important in shape-tuning, unsupervised learning the pre-frontal cortex (PFC) is important in recognition-task specific tuning, supervised learning Bottom line: neurons learn representations for objects until meaning is assigned to the object in the PFC

Overview of the Basal Ganglia

the basal ganglia should actually be called the basal nuclei, since they are all located in the CNS and not in the periphery primary function of the basal ganglia is to function as a feedback mechanism for the thalamus ∙they are very close to each other anatomically they are controlled by the cortex their involvement in the limbic/reward and motor systems make the basal ganglia points of interest in both drug abuse and neurodegenerative disorders that present clinically abnormal movements the nuclei involved in the limbic system are either part of the ventral striatum (nucleus accumbens and olfactory tubercle) or the ventral pallidum (substantia innominate) the nuclei involved in the motor system are either part of the neostriatum (caudate nucleus and the putamen) or the paleostriatum (the globus pallidum) ∙together, the putamen and the globus palldium have a lens-like shape, and they are called the lenticular nucleus there are 3 other nuclei that help control basal ganglia which are often considered to be part of these systems even though they are not technically basal ganglia: substantia nigra (SN), subthalamic nucleus (STN) and the ventral tegmental area (VTA) the largest input to the basal ganglia is the cortex, which signal the basal ganglia via glutamate ∙the somatosensory and primary motor cortex feed into the putamen, providing the majority of the input for motor functions ∙the frontal eye fields and parietal association cortex provide the input that helps initiate and coordinate our thought processes into movement although there are several pathways, each with their own distinct regions of the cortex, striatum, GP/SN and thalamus, there is crosstalk b/w these pathways and the flow from cortex to basal ganglia to thalamus back to cortex is not unidirectional ∙example is a Parkinson's patient who cannot cross through a doorway where the flooring changes from carpet to linoleum unless they have a walker/cane with a laser beam in front of it for them to focus on ∙shows that there is some somatosensory input, even thought it is not part of the classical pathway

ALS Pathway

the fibers enter directly into the dorsal horn and synapse immediately (point A) the interneurons travel through the gray matter until they cross over at the anterior white commissure (point B) and then finally form the spinothalamic tract (point C) the sensory input from the DRG (first order neuron) comes in and immediately synapses in the gray matter) ∙the second order neuron called the neospinothalamic neurons originate in the nucleus proprius and then decussate through the anterior white commissure and travel anteriolaterally ∙they will then ascend until they synapse atht eVPL of the thalamus ∙once you reach the pons, the ALS and DCML will be travelling alongside each other, with the ALS more lateral ∙the third order neuron extends from the VPL and synapses on the primary sensory cortex if you cut the spinal cord, symptoms associated with ALS will be seen in the contralateral side in the dermatomes below the lesion

Overview of the Hypothalamus

the hypothalamus (HT) regulates the central control of visceral functions (through the ANS and endocrine system), affective/emotional behaviors (integrating basic instinct from limbic system and rational thought from cortex), and basic homeostatic mechanisms: ∙BP, blood composition (drinking/salt appetite, blood osmolality, vasomotor tone/vasoconstriction) ∙body temperature (metabolic thermogenesis, complex behaviors, i.e. putting on a sweater) ∙energy metabolism (control of feeding, digestion, metabolic rate) ∙reproduction (hormones of mating, pregnancy, lactation, sexual urges) ∙stress response (blood flow - muscles vs. other tissues, adrenal secretions) ∙sleep behavior (balance of retinol based arousal with pineal melatonin for sleep) it does this complex functional regulation through taking in information from around the body/brain such as pain, olfaction, osmolarity, retinal, etc, looking at that information compared to a biological "set-point" and acting via ANS, endocrine function and behavioral responses to move back to the set point while the HT is well conserved through primates, humans have higher cortical function to help us control the urges that come from the HT

The Indirect Pathway of the Basal Ganglia

the indirect pathway inhibits the flow of movement the MSNs of the caudate and putamen contain D2 receptors, which have an inhibitory effect upon these neurons, causing them to produce less GABA, even if the glutamatergic cortex is exciting them to release their NTs Pathway (backwards) ∙SNr and GPi inhibit the thalamus ∙STN excites the SNr and GPi glutamatergically ∙GPe secretes GABA to inhibit the STN, decreasing the level to which it excites the SNr and GPi ∙the caudate and putamen secrete GABA, which inhibit the inhibition of the STN (subthalamic disinhibition) ∙the striatal complex inhibits the GPe's inhibtion of the STN, so the STN can excite the SNr and GPi →causes an overall decreases in thalamic activity and thus a decrease in cortical activity

Motor Circuits

the motor cortex is highly interconnected with different parts of the brain in a feed forward mechanism (anticipation) ∙you anticipate your next step and the motor cortex sends a signal about what to do next sensory receptors on muscle, or even bone, send back information that eventually returns to motor cortex

The Neuromuscular Junction

the neuromuscular junction is the synapse b/w a lower motor neuron and the extrafusal muscle fiber it innervates the NMJ can best be described as a "Rule of Ones" and looks like a reasonably testable list of 4 things: ∙only 1 motor neuron innervates a muscle fiber ∙only 1 type of input - excitatory input ∙only 1 NT - ACh ∙only 1 receptor - nicotinic ACh receptor (nAChR)

Microscopic Organization of the Spinal Cord

the spinal cord contains both gray and white matter which make up a characteristic H shape the gray matter contains many cell types including lower motor neurons, excitatory and inhibitory interneurons, and glia (astrocytes, oligodendrocytes and progenitor cells) ∙interneurons are the most abundant and a balance of excitatory and inhibitory interneurons is essential to controlled motor function ∙variation in cellular composition of the gray matter contributes to difference sin spinal cord anatomy along its length ventral median fissure - divides the anterior region of the spinal cord into right and left ∙also houses the anterior spinal artery which provides vascular support to the anterior region of the spinal cord

Gross Anatomy of the Spinal Cord Within the Spinal Column

the spinal cord extends from the brain stem to approximately the level of L2/L3 vertebrae and is found within the vertebral column like the brain, it is surrounded by the pia mater, subarachnoid space which contains CSF, arachnoid mater, and the dura mater ∙dura mater forms a sleeve covering the entire length of the spinal cord within the vertebral column and serve to support the spinal cord (via ligamentous attachments to the vertebra) ∙dura also forms dural root sleeves which protect the spinal nerve dorsal root projections as they exit the vertebral column through the intervertebral foramens ∙dura fuses with the spinal nerve epineurium around the dorsal ganglion

Striatal Complex

the striatal complex is made up of striosomes or patches and the matrix surrounding them ∙can differentiate b/w the two histologically by staining for aceythlcholinesterase (AChE), as striosomes are AChE poor and the matrix which surrounds the striosomes makes up the bulk of the striatal complex is AChE rich ∙the striosomes contain large amounts of neuropeptides and opiate receptors, and facilitate cross communication b/w the limbic and motor systems by receiving input from the limbic system and projecting to (and regulating) the SN pars compacta (SNc) dopaminergic neurons, which in turn affect the direct/indirect pathways of the motor system ∙the matrix, receives inputs from the cortex, VTA, and SN neurons via D1 and D2 dopamine receptors, and projects to the GP internal nucleus (GPi) and the SN pars reticulata (SNr), regulating the output neurons of the basal ganglia GABAergic medium spiny neurons (MSNs) ∙dopaminergic signaling via D1 or D2 receptors can occur at the dendritic neck or cell body of an MSN ∙MSNs are 95% of all striatal neurons, as well as the beginning point of both the indirect and direct pathways ∙MSNs are inactive without glutamatergic input from the cortex → not tonically active ∙if the combined signal from the cortex and the SNc dopaminergic neurons allows the MSNs to activate, they release their GABA, though they can also release other neuroactive peptides such as substance P, enkephalin and dynorphin →which signaling molecule is release determines whether the MSN acts in an inhibitory capacity or a neuromodulatory one the first step of the indirect pathway is striatopallidal (b/w striatum and external globuus pallidus) ∙first step of the direct pathway is striatonigral (b/w the striatum and SNr) Striatonigral MSNs express D1 receptors (excited by SNc), dynorphin and substance P ∙striatopallidal MSNss express D2 receptors (inhibited by SNc) and enkephalin

Spinal Enlargements

the thickness of the spinal cord varies with length depending on the incoming and outgoing spinal nerves in the distal cervical and lumbar regions, we see a significant enlargement in the spinal cord diameter ∙roughly corresponds w/ spinal nerves that contain sensory and motor signals associated with the limbs

Pain Molecules

there are hundreds of pain molecules if you cause trauma to skin and rupture cells, molecules in the cells will be spilled out and some of these molecules are involved in triggering pain prominent pain molecules include: ∙ATP ∙Protons (involved in ischemic events) ∙Prostaglandins ∙Serotonin (most 5HT is made in gut and spills out where it is picked up and carried by platelets around the body, when you get a cut 5HT is dumped from platelets and triggers pain ∙Bradykinin (mature bradykinin is formed when you have trauma, directly excitesC fibers and Aδ fibers → also fond in bee venom)

Limbic Basal Ganglia

there are two dopaminergic areas in the basal ganglia: the SN (motor) and the VTA (limbic) cocaine's mechanism of action prevents the reuptake of dopamine

Hypothalamic Regulation

there is afferent information coming into the HT which is basically matched by efferent information going back to the same places to help create all important integration for which the HT is known locations are: ∙limbic system - emotional cues from amygdala and septal nuclei ∙cortex -cognitive regulation of HT impulses which comes from prefrontal cortex (executive function, decision making, understands consequences) ∙brain stem - integrated feedback from body other signals help coordinate integration, including: ∙retinal - helps to regulate circadian rhythms and sleep/wale cycle ∙monaminergic feed input - Raphe nuclei modulate 5-HT (serotonin, locus ceruleus modulates norephinephrine, ventral tegmental area (VTA) modules dopamine release to control hypothalamic functions the key point to understand is that HT integrates autonomic and endocrine functions with behavior

Two things happen in V1

there is an increase in future complexity: building more meaningful representations of the world there is a move toward invariant representations these two are key for object recognition

Vestibular Deficits

these result in balance dysfunction and may be triggered by medication, viral infection, tumor, etc. nystagmus, dizziness, and vertigo are common vestibular defects alcohol changes the specific gravity of endolymph, and makes it difficult to walk in a straight line/pass field sobriety test

Laminar Layers of the Neocortex

top layer (1) is near the meninges and bottom layer is near the white matter Layer 1 = Molecular Layer ∙Acellular ∙description: though it is acellular it does contail apical dendrites of pyramidal cells (these are dendrites coming off the apex of the pyramidal cells) that have many afferent connections Layer 2 = External Granule Cell Layer ∙granule/stellate cells ∙description: these granule cells are small cells with local connections (interneurons) Layer 3 = External Pyramidal Cell Layer ∙many cells (small pyramidal cells) ∙description: these cells project to other cortical regions (do not leave the cortex) either across corpus callosum or on the same side Layer 4 = Internal Granule Cell Layer ∙mainly granule cells ∙description: termination zone for primary thalamic inputs (where thalamus projects to when it ends in cortex) →Which areas have a thick layer 4? sensory inputs such as primary sensory regions (auditory, visual, etc.) Layer 5 = Internal Pyramidal Cell Layer ∙mainly pyramidal cells (larger than layer 3) ∙description: form the corticofugal efferents to all regions of the brain outside the neocortex but not the thalamus →this means they project out of the cortex Layer 6 = Polymorphic layer ∙variety of neuron types ∙description: neurons will form reciprocal projections to the thalamuc nuclei that project to the same cortical column (basically are pyramidal cells that project back to the thalamus)

Touch Afferent Pathways

touch afferents from the spinal cord level travel via the Dorsal Column-Medial Lemniscal tract afferents enter into the dorsal horn and travel along the dorsal column on the ipsilateral side they then synapse in the brain stem and cross over to the contralateral side where they then go through the thalamus and then travel to the somatosensory cortex afferents from the cranial nerves travel via the trigeminal system where they enter at the brainstem, cross over and go to the thalamus then somatosensory cortex

Mechanosensation

touch and pressure are detected at the molecular level through direct and indirect mechanosensation direct mechanosensation involves a mechanosensitive ion channel that is tethered to the intracellular cytoskeleton and to the extracellular "sensor" cells (usually an epithelial or lipid structure) ∙when you deform the extracellular structure, you open up the ion channel ∙so far, only one type of ion channel has been identified indirect mechanosensation involves the release of chemical mediators ∙when you apply stress or pressure, chemical mediators will be released that excite sensory nerves ∙for example, epithelial cells will often release ATP when stress is applied, i.e. when bladder is stretched mechanoreceptors release ATP, which diffuses to nearby neurons, C fibers, and acts on fibers so you feel urge to urinate

Mechanoreceptors

touch and pressure are transduced by specialized mechanoreceptors some are rapidly adapting and respond to changing pressure stimuli and some are slowly adapting and respond to constant pressure 4 main structures of mechanoreceptors in the skin: Merkel's disks, Meissner corpuscle, Pacinian corpuscle and Ruffini's corpuscle ∙Merkel's and Meissner receptors are located superficially on the skin ∙Pacinian and Ruffini receptors are located deep in the skin the receptors each respond differently to constant and changing pressures, allowing us to interpret touch you map a receptor field for these receptors by recording from a neuron or axon randomly in the skin and then going around the skin and touching to see where the nerve fires ∙Meissner's receptors are superficial and have a smaller receptor field, receptors fire in response to changing pressures ∙Merkel's receptors are superficial and have a smaller receptor field, fire in response to constant pressure ∙Pacinian receptors are deep and have a larger receptor field, respond to changing pressure, adapt rapidly ∙Ruffini receptors are deep and have a larger receptor field, respond to constant pressure the density of mechanoreceptors varies depending on region ∙there is greater density in the fingers, lips, tongue, etc., compared to the skin on the torso ∙nose has the lowest touch detection threshold

Touch Fibers

touch sensations (are proprioceptors) are carried by Aα and Aβ fibers these fibers have large diameters, are myelinated and are unimodal ∙large diameters provides decreased resistance and allows the signal to be transmitted quicker ∙myelin provides decreased resistance, which also increases propagation speed speed of conduction of these APs is 40-100msec have unique nerve endings with a specialized structure that contains a bunch of epithelial tissue wrapped around a mechanoreceptor ∙mechanoreceptor senses mechano stress, which impinges on the structure and leads to the formation of the AP

Photoreceptors

two types of photoreceptors: rods and cones ∙they both share a common structure with an inner and outer segment, but have different functions outer segment contains membranous disks with photopigment and is where transduction happens the inner segment contains cell nucleus, which connects to the bipolar and horizontal cells rods are specialized for low light vision, have less spatial acuity and are not color sensitive cones are less sensitive to light, have high spatial resolution, fast adaption and are color sensitive

Motor Neuron Terminology

upper motor neurons originate in the motor region of the cerebral cortex (BA 4) and carry motor signals down to lower motor neurons through the spinal cord via the corticospinal tract ∙they do not directly stimulate the target muscle lower motor neurons connect the spinal cord to muscle fibers ∙they receive input from the upper motor neurons within the spinal cord and directly stimulate the target ∙subdivided into alpha motor neurons which innervated extrafusal fibers (the powerful contractile fibers) and gamma motor neurons which innervate intrafusal fibers (sensory fibers involved with proprioception and stretch/length detection) a motor unit is comprised of an alpha motor neuron and the muscle fibers it innervates ∙the motor neurons originate in the spinal cord and can receive many synaptic inputs due to the large number of dendritic trees ∙it will have a single axon that travels to the target muscle where it can innervate several muscle fibers ∙Remember: a muscle fiber will have a single synaptic input from one motor neuron →the motor neuron, however, can (and does) innervate several muscle fibers a motor neuron pool consists of all of the motor neurons that innervate an entire muscle

Flexion/Withdrawal Reflex

useful when you come in contact with something hot/sharp reflex is mediated by the Aδ pain afferents b/c these are the fast pain fibers in contrast to stretch reflexes, pain and temperature reflexes do not make a monosynaptic connection with the alpha motor neuron ∙instead, makes a connection w/ excitatory interneuron that goes on to stimulate alpha motor neuron flexor muscle that needs to be activated is very large, so there will be recruitment of different segmental layers and fibers will run up and down a tract in the spinal cord called the zone of Lissauer or the dorsolateral tract and the fibers can communicate at different levels to ensure an adequate level of recruitment ∙can also be communication in a tract just outside the gray matter called the propriospinal tract

Transcranial Magnetic Stimulation

using a localized pulsing magnetic field, you can induce a current and either activate or deactivate neurons pros - can create multiple, local and temporary activations/deactivations cons - procedure is invasive

Adaptivity

vestibular system is able to adapt to unchanging stimuli and adjust to ambient sensory input it is also extremely sensitive to slight changes a spring-like connection called a tip link exists b/w a kinocilium and an adjacent stereocilium ∙tip link is connected to a trapdoor of a mechanically sensitive potassium ion channel that exists on stereocilia ∙movements pull open the trapdoor, allowing an influx of K+ and this depolarizes the hair cell the adaptive mechanism lies in the motor protein attached to the tip link ∙inside the kinocilium, calcium enters after movement opens mechanosensitive calcium channels, resulting in depolarization ∙increase calcium from a prolonged unchanging stimulus affects actin filament dynamics, causing the motor protein to slip and release tension, shutting the trapodoor, effectively ending the depolarization ∙as calcium decreases, the motor protein walks upwards along its actin filament to retension the spring and resensitize the tip link

Transduction of Sound

vibrations go through the middle ear, pass through the oval window and enter the fluid in the cochlea small vibrations can travel from the base (oval window) to the apex and back to the base (round window) ∙larger vibrations do not travel as far lower frequency waves reach the apex of the cochlea ∙higher frequency waves are stopped closer to the base Frequency is measured by where the wave is stopped in the inner ear receptors on basal membrane react to different frequencies the inner ear breaks down complex sounds to individual frequencies, and then translates them into a base code ∙each nerve fiber of the inner ear codes a particular frequency ∙hear tone by what is stimulated in cochlea hear can be adjusted for sensitivity b/c nerve fibers both enter and exit the inner ear ∙red nerve fibers are regular auditory fibers that transmit efferent signals arising from compressed air cells ∙green nerve fiber is an efferent fiber TO the inner ear, which serves to regulate sensitivity by controlling the impedance of outer ear cells ∙this function provides humans with a huge range of hearing decibel system: 20dB sound is 100 times (10^2) more powerful than 10dB sound ∙we can differentiate sound b/w 0dB and 120dB ∙sounds larger than 140dB can permanently damage eardrum Outer hair cells act to amplify quiet sound more than loud sound inner hair cells transmit sound to nerve signal ∙inner hair cell does not fire an AP ∙a receptor potential is created from an influx of positive ons from endolmyph of scala media, which acts to open voltage gated calcium channels ∙calcium ions entering the cell trigger the release of NTs

Complexity of Vision

vision starts in the eye and will travel to brain to be processed one third of the cortex is dedicated to vision alone ∙there are 46 identified visual areas the reason why vision is so challenging is b/c there are many variables for the same object such as location, scale and viewpoint ∙brain is faced w/ challenge of not only integrating billions of individual signals to create a coherent picture, but it also has to allow us to recognize big differences in input for the same object (i.e. different fonts for the same letter) while also being able to distinguish the small differences that distinguish b/w things (i.e. distinguishing facial differences b/w people who are dressed alike) vision also includes process of input from retina being translated into body coordination, such as hand eye coordination with catching a ball

Retinal-Ganglion Cell (RBC) Projections

vision starts with light that is transduced into an electrical signal in our retina before traveling through the optic nerve to the thalamus and then cortex we have 2 optic nerves, but they will split and cross the midline so that each eye projects to both sides of the cortex ∙depending on where it projects to the cortex, it will have a different function ∙hypothalamus → circadian rhythms via the suprachiasmatic nucleus ∙pretectum → papillary light reflex ∙superior colliculus → eye movements, "blindsight" blindsight is a phenomenon in which blind patients with V1 lesions (they don't have conscious vision) still maintain the reflexes to respond to visual stimuli ∙not fully understand, but think it involves subconscious visual input from the superior colliculus

Visual field terminology

visual field = what we see, tends to be split into quadrants (upper right, lower right, upper left, lower left) binocular portion of the visual field = visual field seen by 2 eyes monocular portion of the visual field = visual field seen by 1 eye only foveal area of both visual fields = macula ∙the center of the visual field ∙mapped onto a huge part (about ½) of the cortex known as the occipital pole remember to flip! → upper visual field is mapped to the cortex below the calcarine sulcus, while the lower visual field is mapped to the cortex above the calcarine sulcus

Going beyond V1

we have a parietal/dorsal stream ("where") which tells us where something is in space via spatial and motion processing we have a temporal ventral stream ("what") which helps us recognize objects via object processing these two streams diverge after lesions in these 2 pathways result in pathways that correspond w/ their function ∙i.e. ventral stream lesion = agnosias ∙dorsal stream lesion = simultanagnosia (inability to perceive more than a single object at a time), hemineglect

Crossed-Extensor Reflex

what happens when you step on a push pin ∙you have withdrawal reflex in leg that came into contact with noxious stimuli and you have to activate the extensors on the opposite (contralateral) leg so you don't fall over Pathway: activation of the Aδ fibers → activation of excitatory interneurons, which will activate flexors on ipsilateral leg ∙at the same time, there will also be activation of inhibitory interneuron that will send signals for extensor on ipsilateral leg to allow stretch ∙to get involvement of contralateral leg, excitatory interneurons will decussate through the anterior white commissure and will synapse on another set of interneurons →one will be excitatory and activate the extensor of the contralateral leg and the other is an inhibitory interneuron that allows stretch in the flexor of the contralateral leg