Neurobiology Final
What does the summation of many motor action potentials lead to?
Sustained contraction - tetanus is when a muscle fiber cannot contract further
Hypothalamus
"below thalamus" - input to pituitary gland - regulation at endocrine system and ANS - contains pituitary gland at end - controls "primitive" body fx (eating, drinking, sex)
cochlea
"coke-lee-ah" three chambers separated by membrane scala media: fluid is here - organ of corti sits on basilar membrane scala vestibuli scala tympani - this and sv connect at apex of cochlea - ossicles push oval window, perilymph (incompressible fluid) pushes the round window of apex out
Thalamus
"inner chamber" - egg shaped structure at top of brain stem, near center of brain - divided into many nuclei, each with specific function - gateway to the cortex (main source of input and sensory relay station for all except olfactory)
Cerebellum
("little brain"): - 2 hemispheres - layered structure - its surface is convoluted to increase surface area - as many neurons as cerebral hemispheres FUNCTION: balance and coordination of voluntary motor control (new data suggests non-motor fx)
What cortical areas control voluntary movement? How do these parts correlate to the planning of movement?
(-2000 msec) Prefrontal and parietal cortices - judgements about actions and their outcome - inputs from visual and somatosensory cortex (-400 msec) Premotor cortices: SMA & PMA - motor planning - control of complex, "skilled" movements - integration of thalamic and basal ganglia inputs (-100 to -5 msec) Primary motor cortex - movements of contralateral muscles - signal descends down lateral pathway --> spinal motor neurons (0msec) movement
Ion channels
(Assemblies of) membrane bound protein(s) that form openable pore and are membrane spanning due to transmembrane domains Pores responsible for specificity for ions Other parts determine gating (open/close in response to voltage, ligand, etc) Ions pass through diffusion so passive, but may be modulated by other proteins
basilar membrane of cochlea
(flexible membrane at base of organ of Corti) home of hair cells vibrates in response to sound
orientation column
- preferred orientation is maintained for all cells in a column from layer II to layer VI (perpindicular to brain) - preferred orientation changes as you move parallel to brain surface
receptor potential
A slow, graded electrical potential produced by a receptor cell in response to a physical stimulus
Steps of radial migration for a neuron
1. DNA replicates. 2. Preparation for cell division 3. Neurogenesis 4. Multipolar shape as polarity is selected 5. Biopolar neuron with directed growth along radial process scaffold 6. At correct layer, neuron leaves radial process 7-9. Leading process become dendrite, trailing process becomes axon
Gate theory of pain
1. Mechanosensory inputs - branch/synapse on inhibitory neurons - branch ascends in the dorsal column to the medulla 2. Dorsal horn inhibitory neurons synapse on secondary projection neuron 3. C-fiber noceceptor synapse on secondary nociceptor projection neuron that ascends to the thalamus Co-active mechanoreceptor + nociceptor sensory neurons: output suppresses activity of nociceptor (that's why we rub areas with trauma)
Pavlovian olfactory condition (T-maze)
1. Mutagenize flies 2. Training: expose flies to odors A and B (associate 1 oder with foot shock) 3. those flies with normal L&M associate odor with shock 4. during testing, normal flies avoid odor A and will move into arm with odor B 5. collect flies in A chamber - may have L&M defects
How is RMP maintained?
1. Na+/K+ pumps 2. Leak channels (far more for K+, only background levels for Na+) 3. Other than above, membrane is impermeable
Axon growth cone guidance steps
1. Netrin expressed in floorplate and netrin receptors (Frazzled/DCC) are expressed by commissural neuron growth cones - chemoattraction to ventral midline (HIGH netrin) 2. once growth cones have crossed the midline, they express Robo (slit receptor) - grow away from the midline because they are repelled by the slit protein
4 steps of ectoderm differentiation leading to the neural tube
1. Neural Plate Formation - cells of the dorsal midline of ectoderm differentiate into neural plate 2. Creation of neural groove - two ridges and a groove differentiate along the midline of the neural plate 3. Closure of the neural groove 4. Neurulation (formation of neural tube) - neural tube forms when the ridges join and yield a fluid-filled space - the space will develop into ventricles and central canal of spinal cord
Three selections of axons in retinotopic map development
1. Pathway selection (nasal RGC project contralaterally, crossing at chiasm, while temporal RGC ipsi-project) 2. Target selection (within the thalamus, RGC will synapse in the LGN) 3. Address selection (within the LGN, a RGC must make a synapse in the right layer with the correct partner)
trisynaptic circuit of the hippocampus
1. Perforant path - entorhinal cortex --> dentate gyrus granule cells 2. Mossy fibers - granule cells from dentate gyrus --> CA3 pyramidal cells 3. Schaffer collaterals - CA3 pyramidal cells --> CA1 pyramidal cells
Physiological traits of memory
1. Persistence - maintained for a long time following brief period of synaptic activity 2. Input specificity - induced only at appropriately stimulated synapses and not neighboring synapses 3. Associaticity/cooperativity - inputs activated together will strengthen (LTP)
Study into input specificity of memory
1. a photoactivatable glutamate bathes the hippocampal slice and this GFP-labelled pyramidal cell 2. glutamate uncaged near the dendritic spine 3. spine (synapse) show structural changes to support LTP and in response to LTP
Two stages of memory acquisition
1. acquisition of a short-term memory - physical modification of brain caused by incoming sensory information - modification of synaptic transmission 2. consolidation of long-term memory - requires new gene expression and protein synthesis - modification of synaptic connections
Order of layer development through radial migration
1. first cells born --> subplate layer (eventually disappears). 2. next cells --> cortical plate - temporary layer for arriving cells as the mature layers 2-6 are formed 3. development of mature cortical layers (an "inside-out" process) - first to arrive --> layer VI. - next neurons --> V, IV, and so on - newborn neurons migrate past old neurons, which end up deeper in the brain
Spinothalamic (dorsolateral) pain pathway
1. nociceptor --> spinal cord and decussate 2. ascend contralaterally (no synapse in medulla) 3. synapse in thalamus 4. thalamo-cortical projection to S1 cortex (perception of pain) and anterior cingulate cortex (emotional experience of pain)
How do radial glial progenitor cells develop into neural cells? How do they also act as guides)
1. radial glial progenitor cells extend from ventricle to brain's pial surface 2. nucleus of cell migrates upward from the ventricular surface toward the pial surface - the cell's DNA is copied 3. nucleus, containing two complete copies of the genetic instructions, settles back to the ventricular surface 4. cell divides in two, yielding either: - 2 progenitor cells or - 1 progenitor cell and 1 neuron (climb on radial branches to destination)
Steps of directing neurite to attractive signal
1. retract filopodia by breaking down f-actin 2. extend filopodia and lamellipodia by building filamentous actin (adhere to substrate surface and pull growth cone via power of actin-myosin) 3. Build of microtubule polymer behind the new actin filaments 4. Breakdown microtubules in opposite site
dorsal column-medial lemniscal pathway
1. sensory neuron - soma is in dorsal root ganglion - associated with mechanoreceptor - ascending path: dorsal column of spinal cord 2. Neuron of dorsal column nucleus of medulla - decussates in medulla 3. Ascending path: medial lemniscus 4. Synapse in thalamus 5. Thalamic neuron projects to primary somatosensory cortex (S1) of the parietal lobe
Criteria of neurochemicals
1. synthesized and stored within a presynaptic cell 2. released in response to presynaptic depolarization 3. produces a postsynaptic cell response that can be mimicked by exogenous application of the neurotransmitter
What is the smallest ridge touch can detect?
13 nm
Stomatogastric ganglion
26 neurons with full circuit diagram of their connections Much known about the molecular properties of the neurons Large cells, easy to record their electrophysiological activity When isolated in a dish, the circuit can produce this rhythmic CPG for days
VGKC Structure
4 gene products yield 4 equally sized proteins that form a tetramer Each has 6 TM alpha helices, one of which is the voltage sensor - 1 pore loop Pore has 5 internal sites for K+ binding and 2 extracellular sites - different toxins bind to different sites
When is the brain most susceptible to monocular deprivation (MD)?
4-5 weeks of age (a day or two of deprivation changes ocular dominance) - measure in layer 2/3 (where eye-specific inputs from layer 4 are compared) - less synapses and activity For reference: at several months of age, a month or more is required to alter OD
How is the S1 cortex organized into columns? How does this structure lend to the somatotopic map of the body?
6 cortical layers in <1mm of cortex - inputs into layer 4, integration in layer 2/3 - neurons in a column process from same side of the body - different mechanoreceptor inputs are arranged in neighboring columns Cortical magnification: size of cortex devoted to each body part is correlated with the density of sensory input received from that body part - features of touch are extracted: position, orientation, motion, shape and curves
Muscarinic receptors structure
7 transmembrane G-protein coupled activates K+ channel to produce inhibition
Pseudogene
A DNA segment very similar to a real gene but which does not yield a functional product; a gene that has become inactivated in a particular species because of mutation.
Long-term plasticity
A change in synaptic efficacy lasting >1 hour LTP and LDP
What is the notochord and what is its role in the development of the brain?
A flexible rod that supports a chordate's back In development: - defines the midline anterior-posterior axis of the embryo - induces the differentiation of the neuroectoderm and neural plate
Lucifer yellow
A fluorescent dye that is small enough to pass through connexons, revealing neurons that have electrical synapses
shunting inhibition
A form of synaptic inhibition in which the main effect is to reduce membrane resistance, thereby shunting depolarizing current generated at excitatory synapses. Synapse located close or on soma & axon hillock, thus having a greater influence on probability of AP due to PSP amplitude's inverse relationship with distance Opens Cl- channels (Ecl is about resting membrane potential so IPSP=0mV) - high reversal potential so Cl- will love to equilibrium in any direction (set by charge) - thus any EPSP passing through region will be lost
Axonal structure
A long tube covered with myelin with breaks called nodes of Ranvier (with high concentration of voltage gated channels)
Goldman equation
A mathematical relationship used to predict membrane potential Different from Nernst in that it accounts for multiple ions and each of their relative membrane permeabilities
Neglect syndrome
A neurological disorder in which a part of the body or a part of the visual field is ignored or suppressed; most commonly associated with damage to posterior parietal areas of the brain.
Endocytosis
A process in which a cell engulfs extracellular material through an inward folding of its plasma membrane.
Temporal lobe
A region of the cerebral cortex responsible for hearing, language, memory, smell, taste Ventral to parietal lobe, lateral to brain Auditory cortex
parietal lobe
A region of the cerebral cortex whose functions include processing information about touch. Most dorsal cortical structure and caudal to frontal lobe Separated from frontal lobe by central sulcus Has primary somatosensory cortex
on-center ganglion cell
A retinal ganglion cell that is activated when light is presented to the center, rather than the periphery, of the cell's receptive field.
Summation in superior olive
A series of neurons in which the right ear starts from a different direction than the left - summation occur where the impulses reach at the same time, causing AP
lateral geniculate nucleus (LGN)
A structure in the thalamus, part of the midbrain, that receives input from the retinal ganglion cells and has input and output connections to the visual cortex (striate cortex) receives 90% of optic tract axons six distinct stacked layers with L/R and retinal ganglion cell type separation
In situ hybridization
A technique using nucleic acid hybridization with a labeled (marker or fluorescent signal) antisense probe to detect the location of a specific mRNA in an intact organism
In situ hybridization
A technique using nucleic acid hybridization with a labeled probe to detect the location of a specific mRNA in an intact organism.
corpus callosum
A thick band of axons that connects the two cerebral hemispheres and acts as a communication link between them. If cut, people can continue with almost no difference around 200 million axons
Tetrodotoxin (TTX)
A toxin that blocks Na+ permeation through voltage-gated sodium channels, thereby blocking action potentials.
Glutamate ionotropic receptors
AMPA, Kainate, NMDA
Microglia (roles, potential for damage, development)
Act as phagocytes, eating damaged cells and bacteria, act as the brains immune system Participate in synaptic plasticity Uncontrolled microglia may induce inflammation and contribute to degenerative diseases In development, microglia actually develop in yolk and invade developing nervous system
TRP channels
Activated by heat but also some chemicals - each thermoreceptor sensory neuron expresses only 1 of 6 TRP - same receptors that respond to sweet-bitter-umami
Dorsal fibers (what are they, where are cell bodies, polarity of neuron?)
Afferent spinal fibers (carry sensory info to CNS) Sensory somata are outside spinal cord in dorsal root ganglion (DRG) Sensory neurons are unipolar (like one giant axon from receptors to axon terminal with somata off to side)
Postsynaptic potentials (def, travel, factors in relation to distance)
Aka endplate potential (EPP) in neuromuscular synapses graded potentials developed in a postsynaptic cell in response to neurotransmitters - single PSP not sufficient to bring interior to threshold Travel passively - no regeneration so amplitude decreases with time and exponentially with distance PSP decreases with distance due to: - internal resistance (diameter of dendrite) - membrane resistance (open or leaky channels)
When are dendritic spins plastic? What are they necessary for?
All throughout their lifespan (but especially during development) Necessary for learning (experience-dependent modifications in synaptic transmission are thought to occur during learning and underlie the storage of memories)
CLARITY Method
Allows visualization of deep structures without sectioning the brain Brain tissue is treated to preserve proteins and nucleic acids on transparent hydrogel scaffold made of acrylamide (lipids are dissolved)
types of ganglion cells
Also note: M cells have transient responses (hence movement) P cells have sustained responses
Exceptions to the Central Dogma that resolve seeming lack of diversity
Alternative splicing - multiple proteins from same mRNA Post-translational modifications
Phenylthiocarbamide (PTC)
An artificially created substance whose main use is in detecting the ability to taste it; active gene (T2R38) to taste PTC is inherited as a dominant. non-taster allele may serve unknown function or mediate unidentified taste
horseradish peroxidase (HRP)
An enzyme found in horseradish and other plants that is used to determine the cells of origin of a particular set of axons. once injected into axon terminals, move along microtubules towards soma (retrograde)
What causes seizures (in terms of brain activity)?
An imbalance of excitation and inhibition, causing in run-away excitation Usually, when a neuron fires, it activates an inhibitory neuron to inhibit a neuron it is connected to so it doesn't overexcite the neuron (feedback inhibition) In run-away excitation, the neurons overexcite each other (cycle) and seizures can result
Hebbian modification
An increase in the effectiveness of a synapse caused by the simultaneous activation of presynaptic and postsynaptic neurons. - if asynchronous with post-synaptic activity, decreased connection Note: in pic, shows some neurons with connections to both areas and some only with one This is how RGCs segregate into left and right
Limbic system
Another way to classify the brain, grouping the hippocampus, amygdala, and hypothalamus Controls emotions, memories, and arousal
Anencephaly
Anterior/rostral neural tube fails to close Result: forebrain degenerates (fatal)
Apoptosis vs necrosis
Apoptosis- active, orderly and organized; requires energy a plan and enzymatic degradation of proteins/dna; produces neatly packed cell fragments that are recycled - major part of growth and development Necrosis; passive and disorderly; produces cell debris - often result of injury/accident
How was taste studied?
Apply various tastants to taste cells with knockout for most receptors and measure PSPs
Dermatome
Area of skin supplied by dorsal roots of a single spinal nerve Shingles infection shows the boundaries of a single dermatome
What happens to hair cell activity as tones increase?
As it increases, peaks blend together For lower frequency sounds, the nervous system uses temporal coding - hair cells can keep up with speed For medium: - phase-locked cells do not fire on every cycle (thus, ensemble of neurons can fire at 4000/sec, keeping up with medium frequencies) For higher, place code - hair cells are irregularly active (can't phase lock), but only subset of cells on basilar membrane will have peak activity
When are humans able to hear best?
As newborns
What is the relation between size of dendritic arbor in ganglion cells and movement sensitivity?
As size increases, more likely to sense movement (hence M cells, the largest, are best at movement detection)
Synaptogenesis and pruning
As the differentiated cells mature, synapses develop between them so that the cells become connected. First, a surplus of cells develops; later, these will be pruned.
ATP and adenosine signalling
Co-released with other neurotransmitters Binds to ionotropic (P2X) - unique because trimer also bind to metabotropic receptors - adenosine-dependent sleep promotion is blocked by caffeine, leading to stimulant effects
Tripartite synapse model for glutamate
Astrocytes reuptake excess glutamate, converts to glutamine so neuron can absorb and convert back (cannot absorb glutamate), and releases towards presynaptic terminal
salt-sensitive gustatory cells (channel, high vs low [Na+])
At low Na+ levels: - Na+ selective, amiloride-sensitive channel (ENaC) - partially blocked by drug amiloride (a diuretic) - NOT voltage gated - as [Na+] increases, Na+ enter cell and causes depolarization that opens voltage gated cation channels - cell is fully depolarized and releases 5-HT At high levels: - sodium may stimulate bitter and sour receptor cells, perhaps pain receptors - non-specific transduction
Alzheimer's disease (AD)
Atrophy of cerebral cortex and neurodegeneration caused by neuron dysfunction due to 2 cellular deficits - neurofibrillary tangles (NFTs) - beta amyloid plaques
Hair cells
Auditory sensory receptor cells that transduce sound into electrical signals topped with 10-300 stereocilia + 1 kinocilium no axons and no APs - synapse with spiral ganglion cells (form auditory nerve) When stereocilia bend, mechanically-gated K+ channels open or close - K+ influx --> depolarization (because high K+ concentration in endolymph but low in perilymph so gradient exists) --> release of glutamate
When are distinct cortical areas defined in development?
Before the brain is fully innervated - transcription factors organize the regional fate - thalamic input contributes to cortical differentiation (specifies pattern of cortical areas)
Spatial properties of memories on brain vs single neuron levels
Brain level (distributed network) - no single neuron represents specific memory - unique pattern of neuronal activity of many cells - advantage: memories survive damage to individual neurons - "graceful degradation: of memories with gradual neuron loss - widespread projections from association neocortex converge on hippocampal region and ultimately back to same neocortical areas Single neuron level - synaptic strength - physical change of memory --> modification of synaptic weight - increases and decreases in synaptic weights (shift neuronal selectivity and store infor) - synaptic plasticity - long-term potentiation (LTP)
Dendrites (function, structure, length)
Branchlike parts of a neuron that are specialized to receive information. About 2 microns in length, often 5-7 dendritic trees / neuron Contain neurotransmitter receptors in membrane (ligand gated channels that allow for a graded response) All branches together are called the dendritic tree
excitatory postsynaptic potential (EPSP)
Brief depolarization of a neuron membrane - neuron more likely to produce AP Mech: influx of Na+ (opening of Na+ channels)
Types of neurochemicals
Broad classes: - small-molecules - neuropeptides - gasotransmitters (diffuse)
Hydrocephalus
CSF build-up in the skull causing deformity and brain damage through pressure - less bad in babies as skull sutures aren't set so will expand Treated through a shunt (connects to another area where it can be reabsorbed)
SNARE complex
Ca++ sensitive - synaptotagmin: calcium sensor on vesicle Ca++ influx creates calcium micro domain in terminal - calcium then binds to SNARE and changes conformation --> membrane fusion occurs
CaMKII
Calmodulin-dependent protein kinase II; important in forming long-term memories. - most abundant protein in synapse - 1-2% of the brain's protein Structure: - 2 stacked rings of 6 subunits - auto-phosphorylates itself to increase its activity - remain active long past the potentiation stimulus Activity with calcium: - low Ca++: insufficient phosphorylation - high Ca++: phosphorylation outpaces de-phosphorylation
What are the types of striated (striped) muscle?
Cardiac: found in heart Skeletal: attached to bones - responsible for majority of body movements
Axons (function, length and diameter, components)
Carry impulses away from the cell body Often range from 1-20 microns in mammals, though squid giant axon reach almost 1 mm Length can reach over 1 meter Consists of, in order: - axon hillock (near soma, where AP is generated) - axon collaterals (branches of axon) - axon terminals (end, location of synapse)
What are the cause and mechanism of Amyotrophic Lateral Sclerosis (Lou Gehrig's Disease)? What is its prevalence and death rate?
Cause: - degeneration of motor neurons in. spinal cord and brain stem - progressive muscle weakness as motor neurons die - no change in cognitive ability Mechanism: unknown (hence no effective treatment) - 90% of cases have no family history - 20% of familial cases are. associated with SOD-1 mutations - higher rates in athletes and with history of trauma - possible mechanisms include: glutamate excitotoxicity, generation of free radicals, mitochondrial dysfunction, cytoplasmic protein aggregates, disruption of axonal transport, microglia inflammation/toxicity 1:400 women and 1:350 men - peak onset around 60 years - death in 2-5 years
determination vs differentiation
Cell is committed to a particular cell type after determination, but the cell has not yet actually produced the products it needs to carry out the functions of the cell type=goal of differentiation. Transcription factors start differentiation programs and repress other differentiation programs - as development/time elapses, fate potential becomes more and more restricted Both cell-autonomous (intrinsic) and non cell-autonomous factors (environmental/extrinsic) control determination and differentiation - latter is important because in developing system, extrinsic factors are also changing
Ocular dominance columns
Cells from same eye are grouped together in columns perpendicular to the surface of the cortex, cells of each processing similar info within the column
voltage-gated ion channels
Channels that open or close in response to a change in the membrane potential. Important types for AP: - voltage gated sodium channels (VGNC) - voltage gated potassium channels (VGKC)
Conditions of current flow across neuronal membranes (3)
Charge carriers (namely ions) Passageway (channels) Driving force (incorporating electrostatic pressure and concentration gradients)
Protecting the brain
Chemical Protection- BBB(Blood Brain Barrier- tightly packed cells of blood vessels, walls prevent entry of too many molecules) - I'd also say CSF (waste removal) and microglia fall in this category, but not as significant Physical Protection- scalp, skull, meninges, CSF
What guides the growth cones?
Chemoattraction: contact or diffusible Chemorepulsion: contact or diffusible Types of chemicals: - trophic: support the survival of the neuron - tropic: guide axon of the neuron
critical windows of development
Circuits must develop by a certain point in development or else it cannot ever be. resolved - observed in children with cataracts never having normal vision even after cataracts fixed
What is the closed loop of the cortex and cerebellum?
Closed loop refers to how there is cerebellar output to the same cortical area that supplied the cerebellar inputs - circuit function: monitor and modulate its own inputs
ventral horn of spinal cord
contains bodies of lower motor neurons
What are muscles composed of?
Composed of many individual fibers - each fiber is a long, thin cell that runs the length of the muscle
Axon hillock
Cone shaped region of an axon where it joins the cell body. Summation of EPSPs and IPSPs may generate AP here (high concentrations of VGNCs)
Presynaptic terminal
Contains synaptic vesicles High density of mitochondria Active zone: site of neurotransmitter release
Planes of tissue sections
Coronal: front to back, perpendicular to ground and midline Sagittal: parallel to midline Horizontal: top-down, parallel to ground
What are the two cortical inputs into the cerebellum when only examining the corticospinal tract?
Cortex --> pons --> cerebellum - major input to cerebellum - pontine inputs: 20 million. axons Cortex --> red nucleus --> inferior olive --> cerebellum - learning and memory functions - high # of electrical synapses / gap junctions
What are the descending lateral motor pathways?
Corticospinal tract: - longest & fastest - mediated by large pyramidal neurons - direct connections on MN Rubrospinal tract: - learned patterns of movements
What is the mechanism of PD and what are some available treatments?
DA neurons degenerate in substancia nigra and basal ganglia --> subs. nigra's inputs into motor output circuit are lost - increase indirect loop - decrease direct loop Outcome: thalamic excitation to cortex decreases Treatments: - drug treatments to enhance DA in the brain: L-dopa - surgical treatments: deep brain stimulation of STN/GPi
Central Dogma
DNA -> RNA -> Protein
How does critical period change with age? What are five things that end the critical period?
Decreases Stops when... - axons are fully myelinated - synaptic transmission matures (NR2B subunit of NMDA is replaced with NR2A with age, which admit less Ca++) - cortical activation is constrained (modulatory inputs ACh and NE facilitate plasticity and change with development) - extracellular matrix is fully mature (limits structural plasticity) - inhibitory circuitry matures (GABA)
Postsynaptic neuron
Dendritic spine (often, may be tissue) contains receptor proteins Postsynaptic density: location of receptors - looks black on electron microscope
What are the three major inputs to an alpha motor neuron?
Descending excitatory or inhibitory input to generate motor programs Provides feedback info about muscle length and position Initiation of movement and posture control
How can descending pathways regulate pain perception? What is the relevant anatomy?
Descending inputs to sensory neurons in dorsal horn controls their activity (turn up or down the dial) Periaqueductal grey (PAG) neurons contain opioid receptors - stimulating PAG --> analgesia - stimulated by cortical regions that process emotion and endogenous opioids (endorphins, enkephalins) Modulating pain signals in dorsal horn 1. PAG synapse with raphe nuclei / serotonergic neurons 2. Raphe neurons make synapse with enkephalin-expressing neurons in the dorsal horn 3. Enkephalin neurons inhibit pain pathway
Methods of Chemical Signal Termination
Diffuse away (peptide neurochemicals) Transporters into glia Degradation - prominent example is AChE Reuptake by presynaptic terminal Or a combination of above
What are the two motor loops connecting the cortex to the thalamus back to the cortex? What are their respective purposes?
Direct loop: enhances movement initiation and activates motor program 1. cortical activation 2. excites caudate/putamen 3. inhibits GPi 4. release VLo (thalamus) from inhibition 5. activity in VLo boosts activity in motor cortex Indirect loop: antagonizes direct pathway and suppresses motor program 1. cortical activation 2. excites caudate/putamen 3. inhibits GPe 4. release subthalamic nuclei (STN) from inhibition 5. GPi are excited 6. VLo is inhibited and motor cortex inhibited
dendritic length constant (lambda)
Distance from the origin where the depolarization has decayed 37% Slender dendrites have a shorter length constant Myelination increases membrane resistance --> larger lambda - dendrites are not myelinated
Two vesicle pools
Docked (or "readily-releasable") pool - associated with active zone Reserve pool - away from active zone
Why do photoreceptor cells have a GPCR system rather than a light-sensitive channel?
Due to signal amplification, 1 photon --> 500 transducin just 1 PDE destroys thousands of cGMPs in other words, a more sensitive system
Hippocampal potentiation
Early phase LTP - Ca++ causes insertion of new AMPAR and modification of existing AMPAR Late phase LTP - Ca++ activates 2nd messengers and transcription factors (CREB) which cause gene expression (protein synthesis) --> more AMPAR and synaptic proteins
Phases of sodium current due to glutamate
Early phase: fast opening of mainly AMPAR and some NMDAR Late phase: persistent current through the NMDAR Study reverse potential and which ions are responsible
Ventral fibers (what are they, where are cell bodies, polarity of neuron?)
Efferent spinal fibers (carry motor info from CNS, so exits CNS) Motor somata are in grey matter of CNS multipolar
otop-1
Encodes H+-selective ion channel in taste, used in sour-sensitive taste cells in ear, maintains pH to make the otoconia (calcium carbonate crystals in ear that participate in vestibular system) Structure: - dimer of 12 TM subunits (each having similar N and C domains) Through voltage clamp studies, they found cells that express otop-1 respond to pH
What is the purpose of the direct and indirect pathways of the basal ganglia?
Enhancing initiation of some movements while suppressing the competing or inappropriate motor programs Acts as a "gate" over voluntary movements
Pathway of light through eye
Enters through pupil --> focused by lens and cornea --> hits retina (after passing through its many lamina) --> AP travel through optic disk to brain
ENaC
Epithelial sodium channel - trimer channel, each subunit has 2 TM regions - same family as P2X found in kidney, lung, colon
Nernst equation
Equation for 37 degrees Celsius
Speed of electrical synapse
Essentially no time lag between pre-synaptic action potential and post-synaptic potential (PSP) - of course, PSP has far smaller magnitude Faster than chemical synapse
Sperry's eye rotation experiment
Experiment: - rotate eye 180 degrees - question: where will the axons grow? Result: - when neurons regenerate, they make connections with their original targets - topographic map is maintained - animals behaved as if it saw the world upside-down and reversed Implication: chemoaffinity hypothesis - chemical tags that specify each area of the eye/tectum
Antidromic conduction
Experimental Backward propagation
Retinotopy
Feature of visual cortex Map of visual field onto a target structure (retina, LGN, superior colluculus, striate cortex - central visual field (fovea) overrepresented in map
What happens to RMP and AP if intra- or extracellular concentrations of Na+ or K+ are changed?
First off, basics: - at RMP, more K+ inside cell and more Na+ outside - AP involves influx of Na+ followed by efflux of K+ - intracellular increase has same effect as extracellular decrease and vice versa Extracellular K+ increase: - lower voltage difference as exterior is now more positive results in higher RMP (may even cause uncontrolled AP firing if high enough) Extracellular K+ decrease: - lowering RMP further (hyper polarization) Extracellular Na+ increase/decrease: - due to low permeability, does not really affect RMP but changes are directly proportional to magnitude and speed of AP
sympathetic nervous system (SNS)
Flight, fright, fight, and sex
cerebrospinal fluid (CSF)
Fluid (ultra-filtered plasma) in the ventricles of the brain that flows in the subarachnoid space and bathes the meninges. - produced in choroid plexus constantly - complete CSF occur 3x daily and absorbed by blood vessels moved around by cilia Serves to deliver nutrients, remove waste, and absorb shock
Huesar and Reese VGCC and Frog NMJ
Found how VGCC couple the AP to neurotransmitter release Set up a device that electrically stimulated a frog motor neuron terminal as it fell onto a super-cooled copper block and fractures presynaptic and postsynaptic cells apart Allowed for pictures of active zone, showing exocytotic fusion pores formed only where calcium channels were
Where is smooth muscle found and what controls it?
Found in lining of GI tract, within arteries, and in reproductive system Controlled by autonomic nervous system
Where is the primary motor cortex (M1) found and what is it the source of? How is M1 organized in terms of layers and mapping?
Found on the precentral gyrus of frontal lobe Source of voluntary motor control Laminar organization of M1 - output layer = layer 5 (pyramidal neurons) Topographic motor map (contralateral) - more coarse than somatosensory map
What are the different locations of sensory neuron endings and what stimuli do they correspond to?
Free-nerve ending: pain, temperature, itch Sensory structures on muscles and joints: proprioception Encapsulated by specialized structures in skin: touch/mechanoreception
Olfactory cortex
located in front and temporal lobes inputs BEFORE thalamus (unique) widespread influence on forebrain (emotion, motivation, memory)
What is the function of the corticospinal tract? Where does it decussate?
Function: voluntary movements / fine motor control of arms and fingers, hands and feet Pyramidal decussation: 70-95% of CST neurons cross midline at medulla/spinal cord junction - synapse with contralateral distal limb muscle motor neurons
Brain stem
Functions: - Relay point between cerebrum and spinal cord - Regulates critical body functions (breathing, heart rate, BP, body temp) Proximal to cerebellum 4 structures: - Medulla (myelencephalon) - Pons (mesencephalon) - Midbrain (mesencephalon) - Reticular formation (aka reticular activating system; not defined well anatomically)
Telencephalon (cerebrum)
Functions: - conscious thought processes, intellectual functions - memory storage and processing - conscious and subconscious regulation of skeletal muscle contractions Two hemispheres Structures: - basal ganglia - hippocampus - amygdala - cerebral cortex - olfactory bulb
Dynamin
G-protein required for release of clathrin-coated vesicles from membrane (pinches off vesicle)
Olfactory receptor protein
GPCR (indicated by 7 TM) Variation in amino acids (~950 ORP in humans) - some regions are highly conserved - largest single gene family in mammals (3-5% of genome) but many are pseudogenes (60% in humans, yielding only 400 functional ORP) Able to bind multiple odorants Have differing sensitivity to different odorants Are broadly tuned to odorants (show low specificity)
Flow of information through retina
Ganglion takes to thalamus
Metabolic pathway of glutamate
Glia (usually astrocytes) uptake glutamate and convert to glutamine which is pumped out Glutamine uptake occurs in presynaptic terminal, where glutaminase converts to glutamate - then vesicle loading by VGLUT transporter Note: VGLUT is also often used to mark cells
What is the major excitatory neurotransmitter in the CNS? How is it terminated?
Glutamate Terminated by reuptake in neurons and astrocytes
Glutamate and Glycine vs ACh, GABA, and amines
Glutamate and glycine are essential amino acids that are abundant; loaded into vesicles by specific transporters The latter three require specific enzymes to convert a precursor into them and then are loaded into vesicles by specific transporters
Golgi tendon organ circuit
Golgi tendon organ sensory neurons synapse with inhibitory neurons 1b excitation --> inhibitory neuron excitation --> motor neuron inhibition Prevent injury and adjusts power
What gradients establish retinotopy?
Gradients of ephrin ligands and Eph receptors across retina and tectum Pathfinding RGC axons navigate through repulsion and attraction of the gradients of receptors/ligands to the right spot in the target tissue About a dozen different members of this membrane-bound signaling molecule family - participate. in. cell-cell. adhesion - attraction and repulsion.
Two categories of CNS synaptic membrane differentiations
Gray's type I - asymmetrical, usually excitatory Gray's type II - symmetrical, usually inhibitory
Cortical features
Gyri (Gyrus): raised areas = peaks - bumps Sulci (Sulcus): lowered areas = valleys - small grooves Fissure: large sulcus, often an anatomical landmark - major grooves
What is Myasthenia Gravis and what are its treatments?
Immune system produces antibodies that bind to and disrupt the nACh receptor - extreme muscle weakness and fatigue - first symptom is often drooping eyelids Treatments: - immunosuppressants - inhibiting AChE: ACh has higher chance of binding to remaining receptors
Gastrulation
In animal development, a series of cell and tissue movements in which the blastula-stage embryo folds inward, producing a three-layered embryo, the gastrula.
chemoaffinity hypothesis
In neural circuit assembly, axons. and their targets bear matching molecular labels that endow neurons with unique identities and specify synapses between appropriate partners
Weaver mutation
In pore loop of K+ channels in cerebellar granule cells Allows Na+ to enter channel --> increases Vm --> increases excitability --> cell death
Neuron Doctrine
Individual neurons are the basic structural and functional unit of the nervous system Santiago Ramon y Cajal argued for this based on his observations and most agreed based on evidence Eventually proven correct once the electron microscope was developed
Filopodia
long, fingerlike extensions from growth cones of neurites
Rostral migratory stream
Inhibitory interneurons and oligodendroglia generated from a different ventricular site and migrate laterally. Newborn neurons migrate tangentially from radial glia to radial glia - destination: basal ganglia and other limbic structures, as well as GABAergic neurons in neocortex
Radioactive tracer & autoradiography (what are these and example)
Inject a radioactive tracer near neuronal cell bodies and wait about two days so active transport can occur (anterograde transport, so to synapse) Visualize axon terminals by placing tissue on x-ray (autoradiography) Usage: visualizing which parts of brain synapse to right eye vs left eye (tracer injected into eye)
Why was the squid giant axon used in the experiments that first described the excitable membranes of neurons?
Its size meant it could be used in labs easily without the use of a electron microscope and could be inserted with voltage clamp electrons
What is the output circuitry of the motor nuclei of the basal ganglia?
Key features of circuit: - GP has tonic inhibitory GABAergic activity --> inhibition of thalamus - striatal output: GABAergic, transient --> inhibition of GP only when they are stimulated
Motor proteins (mention rates)
Kinesins: move on microtubules from - to + (thus, anterograde or soma to axon terminal) Dyneins: move on microtubules from + to - (thus, axon terminal to soma or retrograde) Both use ATP Two rates: - slow: rates of 1-10 mm/day - fast: rates of 1000 mm/day
Three mechanisms of endocytosis
Kiss-and-run - release without full vesicle fusion (tiny part merges with membrane briefly) - no recycling needed - not all neurotransmitters released - no clathrin used Clathrin-mediated endocytosis - full vesicle fusion --> all neurotransmitters released - recycling occurs away from active zone - slower than kiss-and-run Ultrafast endocytosis and endosomal budding - full vesicle fusion recycling occurs within active zone - clathrin buds vesicles off endosome, not membrane
Pinna
outer ear helps with vertical localization of sound
Ectoderm
outermost germ layer; produces sense organs, nervous system, and outer layer of skin (hair as well)
What are the two major descending spinal motor pathwyas?
Lateral pathways: - originate in motor cortex - voluntary movements of body - fine motor control of arms and fingers Ventromedial pathways: - originate in the brainstem - subconscious, automatic movements of the neck and torso - used for balance and posture
Binocular receptive field in visual cortex
Layer 3, superficial to IVc
Why does target (i.e. limb) elimination increase apoptosis during development while target addition decreases apoptosis?
Less targets = less neurotropin release = more competition for less neurotrophin = more apoptosis as more neurons don't receive enough Opposite for target addition
Photopigment
Located in outer segments of photoreceptors Opsin (GPCR) with a retinal embedded within - opsin varies with pigment - retinal (light absorbing chromophore that induces opsin change) is same for all Rod and cone opsins are all in same family - many AA changes between rhodopsin, S & M - few between M and L
Which photopigments mutate more easily to cause color blindness?
Long, then medium - adjacent on X-chromosomes - more common in men because women have two X-chromosomes (so compensation occurs) - due to misalignment of M and L during the recombination event of meiosis S extremely rare
What is the mechanism of HD?
Loss of caudate --> GPe projections GPe is NOT inhibited, STN is inhibited - STN (indirect pathway) less effective at opposing direct pathway Direct pathway abnormally increased - increased thalamus --> motor cortex Outcome: unwanted motor activity
What is the result of lesions to the descending lateral motor pathways?
Loss of fine motor coordination & independent finger control However, posture is completely OK
G-protein-coupled signal amplification
May result in long-lasting, widespread changes in cell function
What three types of stimuli do pain receptors respond to?
Mechanical Thermal Chemical Most nociceptors are polymodal - present in most body tissues but not the brain
What is the structure of Piezo1 and Piezo2 and where are they found? What data supports it being the mechanoreceptor protein?
Mechanically-gated cation channels found in at least some mechanosensitive receptors 30+ TM domain containing Piezo protein - forms trimer channel ("propeller-like") Supporting data: - retains function when expressed in oocytes or artificial bilayers - expressed in sensory afferents (but not in all) - knockout animals have reduced sensory abilities
Αβ transmission time from toe to cortex
Mechanoreception ~ 50 m/s --> 0.045 s (45ms) from toe to medulla ~ 3 ms for each synapse (medulla and thalamus) Total: ~51 ms
Synaptic vesicles
Membrane bound spheres located inside the axon terminal Contain neurotransmitter Uniform in size/volume
Why is the RMP -70mV?
Membrane is far more permeable to K+ at rest than any other ion, so it is close to EK - background leak of Na+ raises Vm at rest (RMP) to -70 mV
Oligodendrocytes
Myelinating macroglia in CNS Branches to myelinate multiple parts of the axons of multiple neurons
"Tell Di that Mesen Met Myelen"
Mnemonic for brain anatomy from cerebrum to brainstem: - Tell: telencephalon - Di: diencephalon - Mesen: mesencephalon - Met: metencephalon - Myelen: myelencephalon
Occipital lobe (location, function, lateral or contralateral?)
Most caudal region of the cerebral cortex that processes visual information - houses primary visual cortex Visual cortex is contralateral (right eye processed on left brain)
Frontal lobe
Most rostral region of the cerebral cortex that has specialized areas for movement, abstract thinking, planning, memory, and judgement Separated from parietal lobe by central sulcus Notable structures: - prefrontal cortex - primary motor cortex
What is the only thing a muscle can do?
Muscle can only contract - extension or flexion of a joint is determined by which muscle contract - muscles work in antagonistic pairs (flexors and extensors)
How are muscle fibers stimulated to twitch?
Muscle fibers have receptors for ACh Motor neurons (ventral roots) make synapses with each muscle fiber (NMJ) - AP in a motor neuron causes the release of ACh - ACh will produce a single contraction (twitch) in the muscle fiber
Stretch reflex (muscle spindle)
Muscle pulled (tendency to pull back) Feedback loop: - when the muscle is stretched, AP rate of group 1a sensory neuron goes up - when muscle is slack, AP rate goes down Discharge rate of sensory axons is related to muscle length
Schwann cells
Myelinating macroglia in PNS Each is responsible for a single myelin sheath, thus multiple Schwann cells per neuron May. aid regrowth of damaged axons
Patellar Reflex (knee-jerk)
Myotatic reflex (monosynaptic stretch reflex) Steps: 1. muscle stretches (tapped by hammer) 2. proprioceptive sensory neuron AP rate increases 3. this directly excites motor neuron in the spinal cord segment 4. motor neuron fire APs 5. muscle shortens (contracts)
Pons
part of metencephalon switchboard connecting cerebral cortex to cerebellum - 90% of descending axons make a synapse here
What is the outcome of the NGFβ mutation?
NGFβ is a neurotrophin for nociceptors - without a functional protein, C and Αδ die in development, though Αα and Αβ survive Without pain reception, they have frequent injuries and often suffer early death
Synaptic plasticity over minutes
NMDAR-dependent calcium influx (review Mg++ block and how to get rid of it) Changes in phosphorylation (in response to Ca++ levels) The insertion or removal of AMPAR from the synapse Support: - LTP inhibited if NMDAR are blocked and if postsynaptic Ca++ is chelated - postsynaptic Ca++ increase is associated with activation (CaMKII) - AMPAR-phosphorylation is associated with increased conductance and AMPAfication of the synapse
What is reciprocal inhibition and what are its steps?
Neural circuitry prevents antagonistic pairs from being simultaneously active - when one set is contracting, the other is relaxed 1. muscle stretches 2. 1a/A-alpha sensory neurons fires APs 3a. 1a/A-alpha directly excites MN 3b. 1a/A-alpha excites inhibitory IN 4. MN fire APs and flexor muscle contract 5. IN inhibits antagonist MN 6. Antagonist (extensor) muscle does not contract
Two types of synaptic vesicles (color on electron micrographs, size, type of neurotransmitter, and speed/function)
Neurotransmitter vesicles - clear in electron micrographs - 50 nm diameter - for small molecule neurotransmitters - fast excitatory synapse Dense-core/secretory vesicles - dark in electron micrographs - larger diameter (100 nm) - peptide neurotransmitter - slow modulatory synapse
High impact chronic pain (HICP)
New concept that describes those with pain lasting three months or longer and accompanied by at least one major activity restriction
Receptor types for ACh
Nicotinic receptors (ionotropic) - open when ACh or nicotine binds - NMJ of voluntary muscles - cholinergic CNS neurons are lost in AD Muscarinic receptors (metabotropic) - open when ACh or muscarine binds - e.g. in the heart, this hyper polarizes the muscle cell, prevents depolarization and slows the heart rate
Do only antagonists block proteins?
No Antagonists tend to block the postsynaptic receptor Agonists tend to block the reuptake pumps
Is phosphorylation sufficient for long-term memory consolidation?
No, because neither phosphorylation nor the protein molecules themselves are permanent However, protein synthesis is likely involved as inhibition during or after a L&M task results in a failure to remember
Do retinal cells have pigment?
No, extremely transparent to allow light to pass
Norepinephrine (NE)
Noradrenergic neurons increase arousal and vigilance primary neurotransmitter in sympathetic nervous system
Brain directions
Note that some terms (like rostral) are basically synonymous with others (anterior, though this is more of just a direction while rostral is anatomical) Midline splits the hemispheres, so medial and lateral comes from sides
Functional imaging of cortical imaging
Note: at times, pinwheels are observed that fall within ocular dominance columns and have all orientation selectivity
How do RGCs report activity of bipolar cells?
Number of AP
When do neural tube defects occur and what is their rate? What can prevent them?
Occurs ~3 weeks in development 1/500 live births Cell adhesion and migration that occurs during neurulation is highly sensitive to local cellular environment - supplementing mom's diet with folic acid prevents malformation (~up to 90%)
Olfactory transduction
Odorant --> GPCR --> adenylyl cyclase --> cAMP --> cAMP-gated cation channel --> Na+/Ca++ influx (depolarizes) --> Ca++ gated Cl- channel opens --> Cl- efflux (further depolarization, causing receptor potential in cilia) --> action potential generated
Where on the retina does more convergence occur?
On the periphery (200-300receptors : 1 ganglion)
Photoreceptor components
Outer segment (disk membrane folds) - photopigments here Inner segment Cell body Synaptic terminal
Extrinsic factors in development
Outside the cell (non cell-autonomous) Environmental input, hormones, activity levels, trophic factors
Sequence of events in chemical synaptic transmission
Overall speed: within milliseconds 1. preparing vesicles 2. AP arrives at presynaptic axon terminal 3. VGCC open --> Ca++ influx 4. Synaptic vesicle fusion --> neurotransmitter exocytosis 5. Neurotransmitters bind to receptors --> postsynaptic response 6. IPSPs and EPSPs spread toward axon hillock 7. Remove transmitter from synaptic cleft (endocytosis) --> stop response
Stages of AP
PAY ATTENTION TO TIME AND VOLTAGE CHANGES Below are noted by horizontal lines Resting membrane potential (RMP) Absolute refractory period: - Rising phase: Na+ - Overshoot (around peak): transition with both open - Falling phase: K+ Relative refractory period: - Undershoot: leak channels and pump return and maintain RMP
How can AMPAR be inserted into the membrane?
PSD-95 may be scaffold for AMPAR in membrane - more PSD-95 = more AMPAR able to be inserted
Flexor (or crossed-extension) reflex
Part 1: mediated by excitatory interneurons 1. nociceptors are activated 2. axons enter the spinal cord and branch widely --> activate excitatory interneurons in multiple segments 3. excitatory interneurons trigger APs in all flexor muscles of hurt leg 4. you flex all the flexors in your hurt leg and jerk it away from the stimulus Part 2: mediated by inhibitory interneurons 5. reciprocal inhibition of extensors of hurt leg 6. excitatory INs cross to opposite site where they excite extension pathways of opposite leg and inhibit the flexor pathways of opposite leg These two parts allow us to pull hurt leg and not fall
Benefits of myelination
Passive signal is faster but won't make it down axon Constant regeneration would be way too slow Passive signals move faster through myelin, an insulator that stops membrane leak, and breaks called nodes of Ranvier provide spots of regeneration
orbitofrontal cortex (OFC)
Pathway that mediates conscious perceptions of smell
Nicotinic receptor structure
Pentamer: alpha + beta + gamma + delta or epsilon subunits - must contain 2 alpha but can contain up to five permeable to Na+ and K+ (non-selective cation channel) - excitatory PSPs
Rods
Phototransducer long, cylindrical outer segment with many disks 90 million / retina - abundant in peripheral retina Photopigment is rhodopsin - scotopic vision - 1000x more sensitive than cones - best wavelength: blue-green (500nm)
Cones
Phototransducer shorter, tapering outer segment with less disks 4-5 million / retina High density in fovea photopic vision (resistant to destruction) Three cone pigments: - blue (short) (only 5-10%) - green (medium) - red (long) A lot of variation is number and distribution of M and L, no impact on color vision
Retinotopic map formation
Point-to-point correspondence between RBCs (retina) and superior colliculus (tectum) Mapping: nasal --> posterior temporal --> anterior dorsal --> lateral ventral --> medial
Microtubules (features, assembly, presence in axons and dendrites)
Polymerized tubulin dimers arranged in strands - largest in diameter and largest component of cytoskeleton - heterodimers consisted of alpha and beta, resulting in positive (dynamic) and negative (anchor) ends Assembly is regulated by microtubule associated proteins (MAPs) such as tau Axons: microtubules are oriented with + ends toward the terminal Dendrites: mixed orientations, not present in dendritic spines
Metencephalon
Pons Cerebellum
Where is the direction of movement encoded in the brain?
Populations of neurons in M1 fire and indicate best direction through summation of activity (vector) - every cell has a preferred movement direction - all cells "vote" and a movement is executed
Peptide transmitters
Pre-peptide is synthesized and processed into active peptide in RER/Golgi Packaged into secretory vesicles and transported to terminal
Chemical Synapse Parts
Presynaptic terminal Synaptic cleft Postsynaptic neuron Synaptic vesicles
What are the symptoms and possible causes of Parkinson's disease (PD)?
Progressive difficulty in initiating movements - muscle tremors, stiffness, and frozen facial expressions - difficulty in involuntary/reflexive movements which cause coordination/balance problems Causes are unknown: - genetics play role in early-onset but not late-onset - exposure to environmental toxins - head injury Fun fact: drinking coffee lowers chances of disease
Neural tube differentiation
Prosencephalon (forebrain) --> telencephalon, diencephalon Mesencephalon (midbrain) --> mesencephalon (stays same) Rhombencephalon (hindbrain) --> metencephalon, myelencephalon
Transciption factors
Proteins that bind to specific transcription factor binding domains in promotor of genes - either promote or inhibit gene expression
Outer ear
Sound is focused by pinna into auditory canal sound waves move tympanic membrane (eardrum)
Astrocytes
Provide structural and metabolic support for neurons in CNS Most numbers glia in brain and fill spaces between neurons, supporting synapses by regulating chemicals (hence, modern synapse technically called tripartite synapse) Influences growth of neurons Contribute to BBB
What role do the Purkinje cells of the cerebellum play in the motor circuit connecting the cortex and cerebellum?
Purkinje cells judge the two inputs (from the pons and inferior olive) and through plasticity, generates an "error" message that is communicated to thalamus and cortex
Radial migration
Pyramidal cells and astrocytes migrate vertically from ventricular zone by moving along thin radial glial fibers. neurons born near ventricle, shimmy up, and get off at correct cortical layer
What two methods control the force of muscle contractions?
Rate code: alpha-motor neurons varies rate of APs - effective due to NMJ being highly reliable - ACh is released in response to each AP - each AP causes an excitatory PSP in the muscle sufficient to produce an AP in the muscle --> twitch Recruitment (size principle): motor units are recuited by size (small first, largest last) to provide more force - muscles have motor units with a range of sizes
Bitterness
Receptor protein is T2R-containing dimer - 25 different T2Rs in humans, all encoding bitter receptors - activating any one produces same output (same bitter taste) - redundancy protects use from poison
Umami
Receptors composed of T1R1 + T1R3 dimers - T1R1 is a pseudogene in pandas (feeds exclusively on bamboo so no receptor) - bats also lost T1R1
Sweetness
Receptors composed of T1R2 + T1R3 dimers - T1R2 is a pseudogene in cats (has evolved so many mutations that non-functional)
What is the basis of rhythmic movements?
Reciprocal inhibition for a central pattern generator, a neural network that can produce rhythmic output without rhythmic input - pacemaker is NMDAR/Ca++ activated K+ channel core neurons with bursting activity
Color opponency
Recoding of Trichromatic Color Vision, via lateral inhibition from Horizontal cells, into red/green and blue/yellow
Cholinergic
Referring to cells that use acetylcholine as their synaptic transmitter
Medial Geniculate Nucleus (MGN) of thalamus
Relay between inferior colliculus of tectum and auditory cortex of temporal lobe INFO: Hearing
biogenic amines (monoamines)
Released by aminergic neurons found in discrete loci in CNS but project widely Many diverse functions (from homeostasis to cognition) diffused modulatory NT that release NT into extracellular fluid (signaling to many postsynaptic neurons) Nearly all signal with metabotropic receptors (lead to EPSPs and IPSPs) Two types: catecholamines and indoleamines
What can penguins taste?
Sour and salt gene for TRPM5 has been mutated and is no longer functional (environment applied no selective pressure against this)
Alpha motor neurons
Spinal motor neurons responsible for contracting muscles Capable of rapid firing Synapse on muscle at neuromuscular junction (NMJ)
parasympathetic nervous system (PSNS)
Rest and digest
VGNC Structure
Result of 1 gene product 24 TM alpha helices consisting of 4 domains (6 helices in each, named S1-S6) - S4 is the voltage sensor (moves in response to depolarization, in the process causing other helices to move such that the pores open) - between S5 and S6 is the pore and selectivity filter (simply, pore loop) Has binding site for Na+ to remove sphere of hydration (otherwise too big to enter) Two step closing mechanism: - inactivation: "ball and chain" (or cytoplasmic inactivate gate) blocks pore quickly - closing: channel slowly closes after inactivation
Patch clamp study of cGMP
Results: higher concentrations of cGMP --> channel opening
Endocannabinoids
Retrograde messengers lipid molecules, not packaged in vesicles actions: - synthesis induced by high postsynaptic Ca++ levels - capable of diffusing through membranes from postsynaptic to presynaptic neurons - activate CB1 metabotropic receptors (only on presynaptic membrane) --> inhibits presynaptic calcium channels to reduce NT release (feedback) CB1 receptors are the target of active component of marijuana
Nissl bodies
Rough endoplasmic reticulum in neuron
What is the role of the substantia nigra in the motor output circuit?
SN neurons are dopaminergic while neurons of the striatum express either D1 or D2 receptors - D1R: increase activity of cortical inputs - D2R: inhibit activity of cortical inputs DA decreases inhibition to the thalamus and reinforces motor behavior - D1 antagonists --> poor behavior - D2 antagonists --> enhanced behavior
Which hippocampal synapse is stimulated in LTP studies?
Schaffer collaterals (observe CA1 pyramidal cells)
Which taste cells utilize G-protein couple receptors? How?
Sweetness, bitterness, and umami Variation occurs on what GPCR respond to (varies based on cell) all use dimer GPCR - tastants bund to receptor pair - G-proteins activate phospholipase C - increased concentrations of IP3 --> intracellular Ca++ release --> TRPM5 channel --> Na+ enters and depolarizes - ATP released as neurotransmitter through V-gated channel CALHM1 (note, non-vesicular) - ATP opens purinergic P2X receptors on gustatory afferent (postsynaptic) neuron
What is the set-up and results of the Bereitschaftspotential "standby" potential?
Subjects are asked to stare at a stopwatch and remember the time of their actual awareness of intention to move The time they report is much later than the first evidence of neural activity in the prefrontal cortex / premotor cortex - premotor cortex starts firing when the instruction stimulus turns on and stops firing when the movement is initiated
What does convergence determine in ganglion cells?
Sensitivity (more connections mean more likely to fire) Inversely related to acuity)
What do nociceptors sense and what is their general structure / transducing protein?
Sensory receptors that transduce painful stimuli Without them, most die early Free nerve endings with mechanically-gated ion channels that are stimulated by stretching/bending of the membrane, temperature, chemicals
Do taste receptors react to only one of the basic tastes?
Short answer is no At threshold concentrations, sensitive to one stimulus, but at higher concentrations, less selective because they have the capacity to react to more
Myelencephalon (medulla)
Site of decussation (crossing of axons from one side to other) - may organize info (threat on left side --> processed on right --> body goes right)
Unique problems of neurons (4)
Size and polarization of structure (dendrites vs axon) Non-uniform protein distribution Energetically greedy (maintenance of gradient, transport, and synaptic transmission are draining) Cellular transport
Experiment on establishing retinotopy
Slivers of nasal and temporal retina are placed on carpets of alternating anterior and posterior tectal membranes - question: where do the retinal ganglion cell axons want to grow? Results: - nasal RGC axons do not show a preference (normally would. go to posterior) - temporal RGC axons show preference for anterior tectum. (correct) and avoid repellent activity of EphrinA ligands enriched. in posterior tectum
VGKC Function
Slow to open and close (no cytoplasmic inactivation gates)
MEPP (miniature end plate potential)
Smallest unit of activity (generated by single synapse) There is a background level of activity (-0.5 to 1 mV) occurring without stimulation Due to these, PSPs are discrete values
Symmetric vs Asymmetric cell division
Symmetric: expands the progenitor pool Asymmetric: - neurogenesis (but limits pool) - 250,000 new neurons per minute Example: 5 cell divisions - symmetric = 32 neural progenitor cells - asymmetric = 5 neurons and 1 neural progenitor cell
What are the symptoms and causes of Huntington's disease?
Symptoms/features: - progressive disease that produces involuntary, jerky movements (dyskinesia and chorea) and cognitive symptoms - symptoms first occur in adulthood (after you have had children) - death occurs 15 or 20 years after onset of symptoms No cure or effective treatments Cause: loss of functional dominant gene (huntingtin) - aggregates when it contains mutations - accumulates in cells of the striatium --> apoptosis (cell death)
Synaptic proteins
Synaptic vesicle machinery Receptors Structural proteins Kinases Phosphatases Protein synthesis machinery Transport molecules Mitochondria
Quantal analysis of MEPPs
Synaptic vesicles are constant in size and content Evoked PSPs made up of multiple quanta and you can use that to find number of synaptic vesicles released Can be used to determine structural aspects of new synapse without picture
immunocytochemistry (ICC)
Technique that uses antibodies to determine the brain areas or neurons that contain a specific antigen such as a protein, neuropeptide, or neurotransmitter. Steps: - inject epitope (protein, protein fragment) - purify the antibody that is generated by the animal - attach visible marker (can be fluorescent molecule) - in tissue sample, antibodies will bind wherever the protein of interest is expressed
What are the descending ventromedial motor pathways?
Tectospinal tract: orienting response Vestibulospinal. tract: head balance Pontine & Medullary Reticulospinal tract: - sensory information to modify movement - reflex control
Types of PSP summation
Temporal summation - multiple AP from same neuron occur close enough in time to summate Spatial summation: multiple AP from multiple neurons occur close enough in location to summate
Growth of lobes
Temporal, frontal, parietal, and occipital
What happens if the parietal cortex is replaced with the occipital cortex in a rat?
Thalamic inputs invade the donor cortex Whisker barrels formed in donor visual cortex
LGN (lateral geniculate nucleus)
relay nucleus in thalamus that conveys info from superior colliculus to visual cortex; synapse here, neurons go to primary visual cortex in occipital lobe
What is somatotopic map plasticity and what are two experiments that explore it?
The S1 cortex can rearrange itself in response to changes in input activity Experiment 1: removal of one digit - cortex reorganizes so representations of neighboring digits expand into its former area Experiment 2: select digits are stimulated - their cortical representations expand
electrical conductivity
The ability of an object to carry electric current Inverse of resistance
Why is it surprising that humans can create cellular diversity with only 20,000 protein coding genes in our genome?
The central dogma, if strictly true, would mean there is an insufficient amount of proteins to generate actual diversity of cellular mechanisms that exist in a human and certainly not enough for the diversity of neurons in the brain (not even retina!)
electrochemical gradients of neuron
The combined difference in concentration and charge; influences the distribution and direction of diffusion of ions. Direction of this gradient for a particular ion is called the driving force
Cytoskeleton
The internal scaffolding of neuronal structure that support shape and growth as well as provide the pathways for transport Consist of microtubules, microfilaments, and neurofilaments
How does encapsulation change the function of mechanoreceptors?
The laminar structure of the corpuscle acts as a filter so that only transient indentations activate the nerve endings - if dissected off, the axon loses the fast adaptation
Patient HM
The late Henry Molaison, a patient who was unable to encode new declarative memories because of surgical removal of medial temporal lobe structures (hippocampus)
Lateral inhibition
The pattern of interaction among neurons in the visual system in which activity in one neuron inhibits adjacent neurons' responses. In visual system, this is the reason lines are so vivid
electrostatic pressure
The pressure arising from the propensity of charged molecules or ions to move, via diffusion, toward areas with the opposite charge and away from areas with the same charge
electrical resistance
The property of a material that resists the flow of charged particles through it; measured in ohms Inverse of conductivity
Diffusion
The random motion of molecules from an area of high concentration to an area of low concentration.
Tonotopy
The topographic mapping of sound frequency across the surface of a structure, which originates in the cochlea and is preserved in ascending auditory structures, including the auditory cortex. each hair cell has a tuning curve that responds best to a specific frequency that map along length of basilar membrane
membrane potential
The voltage across a cell's plasma membrane. At rest, about -70 mV
Which three stimuli do mechanosensitive ion channels respond to? How are these forces transduced?
Three stimuli: Force applied to extracellular structure Stretching of lipid membrane Deformation and stress on cell's cytoskeleton Cation channels cause depolarizations (receptor potentials) that produce APs once at threshold (spike potential) - mechanoreceptors have unmyelinated axon terminals (the peripheral and central axons are myelinated)
spike timing-dependent plasticity (STDP)
Timing-dependent activity, probably the result of Ca2+ signaling in the postsynaptic cell, that is required for the establishment of some forms of synaptic plasticity. Pre than post: LTP Post then pre: LTD
Limit of histology
Tissue is dead
Mesencephalon (midbrain, two components)
Two sides separated by cerebral aqueduct: - tectum: dorsal, contains superior and inferior colliculi (visual and auditory stimuli) - tegmentum: ventral, contains substantia nigra (dopamine containing pathway facilitating readiness for movement) Damage can result in Parkinson's disease
Structures of Inotropic Channels and Examples
Two types: Pentamer (2 alphas, 1 beta, 1 gamma, 1 delta) - each protein has four transmembrane domains (M1-M4) - Extracellular side has ligand binding loop on M1 - examples: ACh, GABA, glycine receptors Tetramer (two 1, two 2) - 3 TM domains (M1, M3, M4) and one only crossing a leaflet (M2) - Loop of M3-M4 and M1 protein chain serve to bind ligands - examples: AMPA, kainate, NMDA, glutamate receptors
What are the types of proprioceptive control of motor output?
Type 1a: muscle spindle fibers - sense stretch Transduction: - wrapped around muscle spindle that stretches when muscle strains - mechanosensitive ion channels open --> APs generated --> opposing muscle stimulated Type 1b: golgi tendon organs - strain guage - monitors muscle tension Transduction: - muscle contraction squeezes sensory neuron - mechanosensitive ion channels open --> APs generated --> inhibition --> relaxation
Catecholamine synthesis
Tyrosine is an essential amino acid First conversion to L-dopa made by tyrosine hydroxylase (TH), which is thus used as a marker for these cells L-dopa can cross BBB - given as treatment for Parkinson's disease (then converted to dopamine and thus acting as agonist) all catecholaminergic neurons express dopa decarboxylase, but only epinephrine cells express PNMT (last conversion enzyme)
Overlap in taste
Unclear if umami and sweet are distinct cell groups high salt detected by bitter and sour
Lateral types
Unilateral: one side Bilateral: both sides Ipsilateral: different structures on same side Contralateral: different structures on opposite sides
Transcription factors that pattern cerebral cortex
Unique transcription factor expression patterns - A--> P gradient - M-->L gradient Unique combinations give regions of cortex their identity
Neuronal membrane
Unlike a normal plasma membrane, characterized by electrical excitability through proteins maintaining a gradient and allowing rapid charge turnover
Nissl stain
Uses basic dyes to stain nuclei of all cells and Nissl bodies (found only in neurons) - latter part differentiates glia from neurons - allows study of arrangement of neurons in brain (cytoarchitecture) Shortcoming: only shows nucleus
orientation selectivity
V1 cells respond best not to spots of light but elongated bars of a particular orientation - curved response that peaks at preferred orientation
Sensory hair cells
Vibrate inside of the cochlea generating the nerve signals
visual field vs. receptive field
Visual field: what we see - feature of eyes Receptive field: where on retina the light hits / what is activated by the incoming signal - feature of neurons - size determines acuity (think about how detailed fovea is versus periphery, like more pixels) Ex: light from left side of world hits right side of retina, light from above hits bottom, vice versa and et cetera
CaCC experiment
Voltage clamp of olfactory receptor cells - now vary intracellular Ca++ levels (internal patch pipets) Results: - knockout animals lack current - calcium-dependence of current
Why is an action potential all or none?
Voltage gated ion channels do not allow for a graded response. They either open together in response to the Vm reaching the threshold or do not open
Synaptic tagging
Weak stimulation endows synapses with a tag (enabling them to capture newly synthesized proteins that consolidate LTP) - without it, LTP decays An event that would otherwise be forgotten might be seared into LTM - if it occurs within 2. hours of a momentous event that triggers a. wave. of new protein. synthesis
What is deep brain stimulation and how can it help treat Parkinson's Disease?
What it is: surgical procedure that implants electrodes into the subthalamic nuclei that stimulates it (high frequency, about 150 Hz) What it does: reduces abnormal movements - however, does not prevent the disease progression
Artificial Strabismus
When eyes are misaligned - each eye is independently active, layer 3 neurons rarely simultaneously activated by 2 eye inputs - objects in visual space do not simultaneously stimulue corresponding points on the 2 retinas Unlike MD, no change in total activity, but all activity is asynchronous - low binocular inputs
G protein operation
When inactive, 3 subunits float in membrane (alpha bound to GDP) When receptor is active, allows alpha to exchange GDP for GTP - Galpha and Gbeta&gamma split apart and bind to effector proteins (which may include ion channel) - G alpha slowly converts GTP to GDP (slow rate provide time limit)
When is an off-center on-surround ganglion cell most active?
When the center is in the dark and the surround is hit with light (because light in center will cause inhibition)
Where are electrical synapses found?
Where function requires that activity of neighboring neurons / cells be highly synchronized - cardiac and smooth muscle Common during development when coordinating growth and activity is important
Ventricles (and their connections)
While there are 4 overall in brain, actually one continuous space that services whole brain Lateral ventricles: feed cerebral hemispheres - anterior forms at top near cortex - inferior horns under 3rd ventricle third ventricle: in diencephalon Fourth ventricle: in brainstem Cerebral aqueduct: connect 3rd and 4th ventricles Central canal: runs through spine
Where are motor somata located?
Within spinal cord (no special ganglion) in the ventral horn of the spinal cord 3 maps at each segment of the spinal cord: 1. Segmental: rostral-caudal map of the body at each 2. Medial to lateral: axial. to distal muscles 3. Dorsal to ventral: flexors to extensors
Intrinsic factors in development
Within the cell (cell autonomous) Genetic program Transcription factors
Hippocampus (which aspects of memory occur here?)
curved structure located within each temporal lobe, responsible for the formation of long-term memories and the storage of memory for location of objects Forms memory traces for facts and events and stores temporarily but consolidated elsewhere
Olfactory bulb
a brain structure located above the nasal cavity beneath the frontal lobes (part of temporal lobes) Does not synapse in thalamus
Short-term plasticity
a change in synaptic efficacy lasting msec to min Methods: - synaptic depression (NT depletion) - synaptic facilitation (lasts milliseconds, increases presynaptic calcium levels) - post-tetanic potentiation (lasts minutes, increases presynaptic calcium levels)
Reticular Activating System (RAS)
a dense network of neurons found in the core of the brain stem; it arouses the cortex (maintains consciousness) and screens incoming information
amblyopia
a dimness of vision or the partial loss of sight, especially in one eye, without detectable disease of the eye can result from visual deprivation of that eye during development
Reelin
a glycoprotein that regulates the migration of young cortical neurons along the radial processes of radial cells - migrating neurons express receptors to Reelin secreted by Cajal-Retzius cells (transient population of cells of layer I) Mutations/dysregulation associated with schizophrenia, depression, autism, temporal lobe epilepsy, and neurodegenerative diseases
Neural tube
a groove formed in the top layer of differentiated cells in the embryo that eventually becomes the brain and spinal cord built of polarized radial glial cells
Golgi stain
a histological stain that fills a small proportion of neurons with a dark, silver-based precipitate Only a small number, but reveals soma and neurites for entirely
long-term depression (LTD)
a long-term decrease in the excitability of a neuron to a particular synaptic input caused by stimulation of the terminal button while the postsynaptic membrane is hyperpolarized or only slightly depolarized Opposite of LTP
off-center ganglion cell
a retinal ganglion cell that is activated when light is presented to the periphery, rather than the center, of the cell's receptive field
Basal ganglia (also name key structure and implications of damage)
a set of subcortical nuclei that directs intentional movements (coordinates with substantial nigra of midbrain) Damage can result in Huntington's and Parkinson's
Ependymal cells (grown up and developmental roles)
line the ventricles of the CNS Produce CSF and direct cell migration during development
What is a motor unit and how do they vary with specificity / motor control?
a single alpha motor neuron and all the muscle fibers it innervates - each muscle fiber is innervated by a single motor neuron, but one motor neuron may innervate multiple muscle fibers - motor unit pool: all motor neurons that innervate a single muscle Specificity differences (indicated by motor cortex): - fine motor control (fingers): 1:3 ratio - antigravity muscle: 1:1000 ratio
Chemical synapse
a type of synapse at which a chemical (a neurotransmitter) is released from the axon of a neuron into the synaptic cleft, where it binds to receptors on the next structure (either another neuron or an organ) - Majority of neurons - Specific receptors (selective) - Unidirectional - Variable reliability
electrical synapse (def, traits)
a type of synapse in which the cells are connected by gap junctions - In minority of neurons - Connected cells are electrically coupled - Non-selective - Bidirectional (pre- and post-synaptic decided by signal direction) - Reliable
two point discrimination
ability to distinguish the separation of two simultaneous pinpricks on the skin body is not equally sensitive to touch - fingers have best discrimination because they contain mechanoreceptors with small receptive field sizes
Electrical coupling
achieved with gap junctions depolarization occurs in both cells, resulting in two neurons activating as if they were one
Ion pumps
active transport proteins that move selective ions across the membrane against driving force Consume roughly 70% of brain's energy Notable examples: - Na+/K+ pump - Ca++ pump
Epinephrine system
adrenergic neurons have limited role in CNS, as it is released largely from adrenal glands
Calcium-gated chloride channel (CaCC)
aka anoctamin (ano2) and TMEM16 Function: - activated by cytosolic Ca++ - olfactory transduction and fluid secretion (sweat, guts, pancreas) - highly conserved (worms, yeast) Structure: - 8 TM domain - homodimer
outer hair cells
amplify auditory signal 3 rows of 12000 receive feedback inputs from auditory brain stem that modify shape and increase response of basilar membrane
zona incerta
an area of the midbrain that participates in the initiation of drinking behavior
superior olive
an early brain stem region in the auditory pathway where inputs from both ears converge - judges interaural differences
tip link
an elastic filament that attaches the tip of one cilium to the side of the adjacent cilium
inhibitory postsynaptic potential (IPSP)
an inhibitory hyperpolarization of the postsynaptic membrane of a synapse caused by the liberation of a neurotransmitter by the terminal button Often Cl- influx or K+ efflux
Tauopathy (when discussing mechanism, mention AD specific as well)
any disease that is associated with abnormal accumulations of the protein Tau, forming neurofibrillary tangles that impair the normal function of neurons Mechanism: - Tau organizes and stabilizes microtubules - In AD, kinases improperly phosphorylate tau, which now disconnects from microtubules for NFTs (enhanced by beta amyloid plaques) - without tau to organize them, microtubules separate and collapse - accumulation of tangles and loss of microtubule function causes neurons to due
Myasthenia gravis
autoimmune disease (body attacks AChR) interferes with neurotransmission between motor neurons and skeletal muscle fibers afflicts ~1 of every 10,000 people Muscle weakness (often first in eyelids and eyes) Weakness improves with inhibitors of AChE
How many connections can a single neuron have?
axon inputs from potentially thousands of other neurons 50,000+ connections on dendritic spines
orthodromic conduction
axonal conduction in the natural direction (from cell body to terminal buttons)
AP influencing factors
axonal diameter (bigger = faster AP) # of open channels (faster regeneration) Myelin (facilitate current flow)
Neurites
axons and dendrites
Steps of retinogeniculate-cortex refinement before and after eyes open as well as with experience
before: axons have arrived in cortex and map not formed just after opening: rudimentary eye fields form as axons retract and expand their territories with experience: refined crisp ocular dominance columns
Complex cells of V1
binocular, orientation-selective, ON or OFF responses to bar of light Unlike simple cells, no distinct ON and OFF regions - active if bar of light falls anywhere within receptive field - precise position of bar stimulus is not as important Receptive field built out of simple cells - can respond to moving lines
simple cortical cells (in V1)
binocular, orientation-selective, elongated ON or OFF area flanked with antagonistic surround respond best to bars of light of particular orientation in a particular area of visual field (ON response) Bars of light that do jot align or are outside the receptive field produce weak and inhibitory responses (OFF response) Receptive field built from multiple on/off receptive fields of retina --> LGN
On bipolar cells
bipolar cells that depolarize when receptor cells are hit with light express mGluR (glutamate metabotropic receptor) - when active, G-protein cascade suppresses cation channels - thus, depolarized when less glutamate b/c receptor cell is active Synapse with and excite ON ganglion
OFF bipolar cells
bipolar cells that hyper polarize when receptor cells are hit with light express inotropic glutamate receptors that open when activate (depolarize in dark because more glutamate) Synapse with and excite OFF ganglion
NMDA receptors
both voltage and ligand gated Na+ and Ca++ channels - thus, its activity is dependent on nearby AMPA opening first at rest, magnesium blocks the channel even when channel is open once ligand binds - voltage change when ligand is bound ejects this
Ligand binding and receptor detection
bound radio-ligand revealed on film or PET scan
Axon terminals
branches at the end of the axon forms pre-synaptic component of synapse - contains neurotransmitters in synaptic vesicles (made in and imported from soma as AT has no rough ER) Consists of abundance of membrane proteins (many unique to axon) and large number of mitochondria
anterior commissure
bundle of axons that connects the two hemispheres of the cerebral cortex
dorsal horn of spinal cord
cell bodies of neurons receiving info from sensory neurons
Soma (def, size)
cell body of a neuron usually 10-25 microns
ocular dominance columns
cells from same eye are grouped together in columns perpendicular to surface of cortex cells within a given column process similar info
Glia
cells in the nervous system that support, nourish, and protect neurons total numbers match neurons "glue"
CNS
central nervous system; brain and spinal cord Encased in bone
Fovea
central portion, responsible for acute and detailed vision - packed tight with receptors - nearly free of ganglion axons and blood vessels (small dip due to this) - each receptor in the fovea synapses with a single bipolar cell and single ganglion cell - low/no convergence (each receptor has direct line to brain)
Mechanisms of tetanus and botox
cleaves SNARE complex proteins and prevent exocytosis result: muscle paralysis, possible suffocation if diaphragm effected
Ganglion
collection of nerve cell bodies in the peripheral nervous system
Epilepsy
common (1% of population) often the rhythmic firing of large groups of neurons that is initiated in small foci of the cortex Etiology: - trauma mutations in voltage gated Na+ channels - mutations in GABA channels Common treatment: GABA agonists (stimulate more activity)
Antisense probe
complementary to mRNA
Purinergic signalling acceptance
derived from ATP not accepted as neurotransmitter for a long time due to such a vast amount of ATP in cells that it was almost thought of a coincidence that it was released
Growth guidance cues
diffusible molecules that are released from the ventral spinal cord and produce a gradient Chemoattractant (netrin) or chemorepellent (slit)
What do taste receptors respond to? How do we process flavor?
dissolved compound (often in saliva) Salty, bitter (ions), sweet, sour, and umami (MSG) Thresholds can indicate how much the body wants/doesn't want something (we have very low thresholds for bitter things) Foods elicit distinct patterns of activity and the brain combines this information with mechanosensory and gustatory information to distinguish flavor
Catecholamines
dopamine, norepinephrine, epinephrine synthesized from tyrosine
Dopamine system
dopaminergic neurons largely found in substancia nigra (initiation of motor output) and ventral tegmentum (reward, motivation, addiction)
Reading a IV graph
downward: positive charge entering cell (cations in, anions out) Upward: negative charge entering (anions in, cations out)
Meninges & space within (+ possible disease)
dura mater, arachnoid mater, pia mater (DAP) - layers of connective tissue (dura mater is dense, pia is more mesh-like) Subarachnoid membrane: - CSF and blood vessels (where exchange occurs) 3 layer that provide protection Meningitis (inflammation, very infectious)
Cytochrome oxidase blobs
each blob centered in an ocular dominance column receives koniocellular inputs from LGN Purpose not quite clear, but activity suggests color-processing pathway
Olfactory population coding
each receptor cell expresses 1 of the 950 ORP and may respond to multiple odorants large populations of receptor cells encode a stimulus odorant is recognized by the combined activity of multiple cells
Cortical modules
each small basic unit of space that contains all components necessary to make sense out of a small area in the visual field - orientation, directional movement, color, and depth V1 is made up of ~1000 cortical modules, each being 2mm x 2mm
Emx2 and Pax6
establish opposing gradients in the cortex - cross repress the expression of one another Emx2 is expressed in posterior - without it, anterior areas expand Pax6 is expressed in anterior - without it, posterior areas expand
Betz cells
extremely large pyramidal neurons of the primary motor cortex that synapse directly on motor neurons in the lower regions of the spinal cord. make-up a subset (5%) of the Layer 5 pyramidal neurons - among the largest in humans
Zygote
fertilized egg (results from fusion of egg and sperm)
Hair cells at rest
few channels open low level K+ enters hair cell - low level depolarization - Ca++ can enter - low levels of glutamate released
Immunohistochemistry (name. example)
localizing antigens or proteins in tissues using labeled (colored or fluorescent) antibodies E.g. rabies virus moves retrograde to soma, replicates and explodes - by dyeing, we can visualize neurons
Frequency response of basilar membrane
from base to apex, resonates with increasingly lower frequencies - high frequencies best encoded near oval window
CREB (cAMP response element binding protein)
functions to regulate expression of genes - regulates gene expression required for memory consolidation - binds to DNA that contains CRE in promotor Evolutionarily conserved transcription factor controlling L&M - critical to learning and memory across all species studied - mutant CREB mice or flies do not exhibit conditioning - mutations associated with dementia Types: - CREB-2: repressor of gene expression - CREB-1: activator of gene expression
NMDA receptors
glutamate gated + unique properties - voltage gated Mg2+ blocks pore at rest - conducts Ca2+ - magnitude of Ca2+ flux signals the level of pre- and postsynaptic coactivation
AMPA receptors
glutamate gated ion channels activity plays part in opening NMDA receptors
amino acid neurotransmitters
glutamate, GABA (CNS) glycine (spinal cord) Most abundant neurotransmitters in brain - typical or classical neurotransmitters
Detection of amplitude
greater amplitude bend cilia more and let in more potassium - also activate more hair cells
What is muscular dystrophy and what mutation causes it?
group of inherited diseases characterized by muscle degeneration - progressive weakness and degeneration of muscle - no effective treatments Dystrophin - one of the biggest genes in our genome - 2.6 million base pairs - that makes it more likely to have. a random mutation - encodes large protein that helps link muscle cytoskeleton to extracellular matrix - in disease, muscles tear themselves apart with normal contractions
Growth cone
growing tip of a neurite Components: - lamellipodia (flat, sheet like extensions from core of growth cones) - filopodia (very fine, tubular outgrowths from the growth cone) - actin filaments (provide force to pull the growth cone after filopodium lathes onto other cells or extracellular matrix)
Lateralization of cerebrum
hemispheres of brain have lateralized function left: analytical tasks, language Right: spacial thinking, ability to create, think about images NO evidence for left/right dominant personalities - both hemispheres operate together with no dominance
AMPAR changes with high and low activity levels
high freq stimulation --> high Ca++ --> kinase activity --> AMPAR phosphorylated and inserted and immobilized - activates CaMKII - LTP low freq stimulation --> low Ca++ --> phosphatase activity --> AMPAR dephosphorylated and removed (endocytosis from membrane) - activates Protein Phosphatase 1 (PP1) - LTD
Diencephalon
hypothalamus - pituitary gland thalamus pineal gland
Purpose of chemical senses
identification of nourishment, poison, conspecifics, predators, a potential mate, etc Older and most common sensory system (gustation, olfaction, chemoreceptors)
Coincidence detector for glutamate
if the cell is already active due to AMPA and if it is receiving signal (ligands)
Methods to detect receptors and neurons in the brain
in situ hybridization Immunohistochemistry/immunofluorescence Ligand binding
Astereognosia
inability to recognize objects with touch result of damage to posterior parietal cortex
Anosmia
inability to smell ability decreases with age thin passageways taken by olfactory receptor cell axons through the cribriform plate make them susceptible to damage Also, if hit in face, damage can cause this Associated with neurodegenerative diseases (AD, Parkinson's) and psychiatric (schizophrenia)
Sound-induced movement of basilar membrane
increase or decrease amount of K+ entering hair cell - further depolarizes or hyperpolarizes hair cell Ca++ enters or channels close increased glutamate release or not released sound causes back and forth movement and brain will interpret this pattern of activity receptor potential is greatest when stereocilia move toward kinocilium
What is hyperalgesia and through what mechanism does it operate?
increased sensitivity (reduced threshold) for pain - primary: injured area - secondary: surrounding area operates through inflammation (injury-triggered release of neurochemicals) - bradykinin & prostaglandins are released at the site of injury and activate/enhance nociceptor activity - substance P is released by nociceptors and cause vasodilation and histamine release - secondary: Αβ mechanoreceptors are modified for pain histamine release causes itch - usually a brief, minor annoyance but can become a chronic, debilitating condition - histamine receptor activity --> TRPV1 channels - many itch responses are not responsive to antihistamines
labeled line hypothesis
individual taste receptor cells are specifically tuned for each stimuli - 1 receptor protein type/cell supported when studying receptors at low concentrations
Antagonists
inhibitors --> reduce the activity of a neurotransmitter - block the postsynaptic receptor - interfere synaptic vesicle loading - decrease neurotransmitter release
GABAergic chandelier cell
inhibitory neuron that synapses on axon hillock and thus can override hundreds of excitatory neurons synapsing on dendrites
Biomimetic hearing
insects like the fly and cricket have exceptionally acute directional hearing despite not big enough distance between ears for temporal coding has horizontal plate that provides direction - mechanism investigated for hearing aids
What is the role of the cerebellum in movement?
instructs the motor cortex on direction, timing and force - compares what is intended with what has happened does not initiate movement but coordinates motor activity during a sequence of movements
Duplex theory of sound localization (horizontal plane)
interaural time delay - due to concentric wave nature of sound, waves hit ear at different angles at different times - each ear is hit by different phase of wave if at angle (microsecond differences are detected) (low frequencies are best detected) Interaural intensity difference - sound at one ear is less intense because of head's sound shadow - high frequencies are best detected
Cl- equilibrium potential in olfactory cells
internal = external [Cl-] Ecl- = 0mV - creates driver for Cl- efflux
Blood supply of brain
internal carotid arteries and vertebral arteries
Posterior Parietal Cortex
involved in somatic sensation, visual stimuli, movement planning, attentiveness - where you recognize/interpret the things you are touching
types of postsynaptic receptors
ionotropic - NT binds directly to receptor and causes channel to open metabotropic - receptor is not directly associated with ion channel - instead, NT binding activates G-proteins that move and open ion channel and/or activate second messenger system
glutamic acid decarboxylase (GAD)
key enzyme in GABA synthesis good marker for GABAergic neurons (major source of synaptic inhibition in CNS) - can be used for immunocytochemistry (better than GABA directly because that is released)
Population coding (distributed across-fibre model)
large numbers of broadly tuned neurons (receiving inputs from the activity of multiple receptor proteins) Far more support, due to explaining activity at low and high concentrations
Ageusia
lesion to gustatory pathway and loss of taste perception
AMPA receptors
ligand gated Na+ channels creates voltage change for NMDA to open
deafness causes
loss of hair cells is #1 cause often, auditory nerve is intact, in which case cochlear implants may restore hearing - coil of electrodes differentially stimulate different regions of cochlea based on basilar membrane movement, replacing hair cells - not as accurate as biological mech but better than deafness
Actual loudness vs perception of loudness
lowest and highest frequency sounds are perceived as softer than they actually are - we respond best to voice range
Glutamate metabotropic receptors
mGluRs
Intensity range of human vision
magnitude of 10 billion from brightest to dimmest
visceral (autonomic) nervous system
manages vital functions of the body without conscious effort / awareness Consists of: SNS, PSNS, enteric, and endocrine systems (technically both CNS and PNS)
Driving force
mathematically, difference between Vm (membrane potential) and Eion (equilibrium potential) Proportional to rate of movement
Rhombencephalon (hindbrain)
metencephalon and myelencephalon In other words: medulla, pons, and cerebellum (together vital body processes)
Mesoderm
middle germ layer; develops into muscles, bone, and connective tissue, as well as much of the circulatory, reproductive, and excretory systems
Agonists
mimics neurotransmitter --> produce/enhance the activity of a neurotransmitter - activate the postsynaptic receptor directly - increases neurotransmitter release - increase neurotransmitter production - inhibit degradation enzymes - block reuptake pumps
Cytochrome oxidase
mitochondrial enzyme used for cell metabolism staining indicates areas of high metabolic activity
anterograde transport
movement down the axon away from soma Kinesins
inner ear
movement of fluid in cochloa causes basilar membrane to vibrate, stimulating hear cell sensory neurons --> hair cells release glutamate --> stimulates spiral ganglion cells of auditory nerve ==> project to hindbrain
retrograde transport
movement up the axon toward the soma dyneins
What are the four sensory control mechanisms of spinal motor neurons?
muscle spindle proprioception 1a/a-alpha - muscle length info golgi tendon organs proprioception A-beta/1b - feedback on degree of muscle contraction or force joint, mechanoreception A-beta - info about position and movement from mechanoreceptors in tissue around each joint nociception (alpha-delta fibers) - withdrawal reflex inputs
White matter
myelinated axons
Long term synaptic potentiation
near simultaneous (tetanic) repeated stimulation of the same neurons strengthens their synaptic connections in an experiment where this is done, the LTP evoked increases over time NMDA receptors serve as Hebbian detectors of simultaneous presynaptic and postsynaptic activity Ca2+ entry through the NMDA receptor channel triggers the biochemical mechanisms that modify synaptic effectiveness - increases maturation, responsiveness, reliability, and synaptic responses
Cranial nerves
nerves that directly exit from brain stem and inner head mostly 12 pairs Some are CNS, some are PNS, some sensory, motor, or both (mixed) Vagus ("wanderer") nerve is the exception because it wanders throughout the body
Reticular Theory
nervous system is a net-like structure (diffuse neural network) - analogy would be the circulatory system Camillo Golgi argued for this but it has become obsolete
Activity dependent synaptic rearrangement
neural connections that are used more are stronger; neural connections that are not used are eliminated refines the sloppy map established throughout axon guidance vastly decreases after critical period
Sour-sensitive taste cells
respond to high acidity - H+ enter cell and block a K+ leak channel, causes depolarization (PSP) - V-gated cation channels open and cell fully depolarizes, releasing 5-HT
Processing at MGN and cortex
neurons excited by certain frequencies and inhibited by neighboring frequencies - together, sharpen response and allow us to discriminate very small freq diferences Primary (A1): - columns respond to single freq - tonotopic map maintained secondary: - activated by complex stimuli like speech and music - separate pathways process what and where of sound
Direction selectivity
neurons fire AP in direction dependent response to moving bar of light V1 cells that synapse with M cells
Olfactory temporal coding
neurons in olfactory system are known to produce oscillations of activity in response to odors (unknown why) presentation of odorants to receptors alter: - latency of spikes (timing) - number of spikes - synchrony of spikes timing of AP represents sensory info in ways not yet understood
PSP summation (def, NOT types)
occurs all over neuron, but mostly happens near the axon hillock at the axon initial segment integration of IPSPs and EPSPs to determine threshold
Olfactory epithelial organization
olfactory epithelium is organized into a few large zones each zone contains receptor cells that express a subset of olfactory receptor genes different cell types are randomly distributed throughout their zone each receptor cell expresses 1 olfactory receptor protein (monogenic/mono-allelic expression)
Olfactory information pathway
olfactory receptor cells --> glomeruli in olfactory bulb --> mitral cells --> olfactory cortex --> medial dorsal nucleus of thalamus --> OFC
Divergence
one neuron communicates with multiple neurons in a network does not occur in olfactory system
Convergence
one neuron receives input from multiple neurons in a network increases sensitivity (more probability of AP) in olfactory system, mitral cell in glomerulus is where olfactory receptor cells converge
VGNC Function / Localization
open sodium channels in response to a threshold of -65mV Initiate and transmit the action potential as Na+ enters through the channel Heavily concentrated at axon hillock and nodes of Ranvier (generation and regeneration areas)
Olfactory maps (spatial sensory maps)
particular odors induce activity in olfactory bulb neurons in complex, reproducible spatial patterns in the cortex unlike other senses, the map does not correlate with the sense (nothing to map as smells vary)
3 mechanisms of taste transduction
pass directly through ion channels bind to and block ion channels bind to g-protein couple receptors and activate second messenger to open ion channels
PNS
peripheral nervous system; the sensory and motor neurons that connect the CNS to the rest of the body Not encased in bone
Optic chiasm
point at which optic nerve fibers cross in the brain (site of decussation) - small portion does not decussate
Spina bifida
posterior/caudal neural tube does not form or fails to close often can be repaired
Clathrin
protein that coats the inward-facing surface of the plasma membrane and assists in endocytosis through invagination of the membrane In neurons, clathrin cage supports reformation of vesicles and creates uniform size
What do mirror neurons do and what are they hypothesized to be involved in? Where are they located?
provide a neural basis for everyday imitation and observational learning - fire when one does something AND when watching someone do something (similar activity for similar activity) Perhaps neural basis for empathy as well - hypothesized to dysfunction in autism --> accounting for lack of social/psychological skills Located in premotor cortex
Gap junctions of electrical synapse
provide cytoplasmic channels between adjacent animal cells, allowing ions and small molecules through Formed of two connexons (hemi-channels), each formed of 6 connexins - about 1 nm diameter (wider than pore of V-gated channels
benefit of refractory period
provides directionality for AP Occurs because once inactivated, sodium channels cannot be opened for a while In relative refractory period, can be opened with larger impulse, thus also providing a variety of impulse rates that can be interpreted by brain
What is the structure of somatosensory afferents?
pseudounipolar neurons - cell bodies found in dorsal root ganglion - sensory neuron endings
Phasic receptor
rapid display adaptation rapid decrease in frequency of AP
Horizontal cells
receive input from photoreceptors outside of the bipolar cell's direct photoreceptor connections and project by synapsing on photoreceptors and bipolar cells' synapse Inhibitory (GABAergic) - regulate amount of NT that the receptor releases - responsible for lateral inhibition Make gap junctions with each other
superior colliculus
receives 10% of inputs guides movements of eyes and head towards objects of focus ancient/conserved visual processing area of the brain - midbrain optic tectum (non-thalamic) - small animals may only have this and no visual cortex (e.g. frogs) due to this alternate pathway, individuals with blindsight can still process visual information without conscious awareness
What is somatosensory adaptation and how is it determined?
receptor activity declines despite constant stimulation Two adaption speeds based on the receptor: - tonic (slow/no adaptation) - phasic (rapid)
What makes touch different from all other senses?
receptors are distributed across the body, inside and outside it also consists of multiple senses
metabotropic receptors
receptors that are associated with signal proteins and G proteins (second messenger mechanism, so indirect)
Ionotropic receptors
receptors that are coupled to ion channels and affect the neuron by causing those channels to open Direct signaling
Which cones code for yellow?
red and green
Visual cortex
region in causal most part of neoceotex (i.e. of occipital love) that processes visual info Laminar structure: - layer 4 is discrete input layer - layers 2/3 process but also output (pyramidal cells, especially in layer 3) - layers 5, 6 are also output eye-specific inputs maintained RGC inputs maintained Visual field map maintained - essentially, LGN served to organize information and send to proper places in visual cortex
NO (nitric oxide)
retrograde messenger; can diffuse through membrane because gas - better to think about as affecting vicinity rather than specific cell synthesized from arginine by NO synthase can coordinate many cells' actions No specific receptors and breaks down rapidly - interacts with intracellular proteins to produce cGMP --> activating 2nd messenger systems
tectorial membrane
rigid structure above organ of corti stereocilia of hair cells are in contact with it - separate connection / pivot point that is independent of basilar membrane movement is independent of basiliar membrane
semaphorin 3A
secreted by cells in the marginal zone (superficial layer) repels pyramidal cell axons attracts the growing apical dendrites
pineal gland
secretes melatonin
Three parallel pathways of V1
segregated in retina and LGN Only a model, in reality not this discrete
SSRIs
selective serotonin reuptake inhibitors As name implies, targets presynaptic transporters to slow serotonin reuptake and thus allow signal to continue for longer
Olfaction
sense of smell some odorants are perceived differently at different concentrations enantiomers also smell different to us
Cyclic nucleotide gated channels (CNG)
sensory transduction in olfaction and retina 6TM domain with pore loop - C-terminal, intracellular cyclic nucleotide binding domain Tetramer cation channel - similar to K+ channel
Serotonin (5-HT)
serotonergic neurons in raphe nuclei (brainstem) regulate mood, sleep, and appetite synthesized from tryptophan termination of signal: reuptake into presynaptic terminal, loaded into vesicles or degraded by MAO
Indoleamines
serotonin and melatonin synthesized from tryptophan
Depression drug therapy
serotonin dysfunction associated with depression - thus, antidepressant drugs often block reuptake and inhibit enzymatic degradation SSRIs (selective serotonin reuptake inhibitors) increase the level of extracellular 5HT
What was HM's main symptom resulting from his lobotomy?
severe anterograde amnesia - impaired declarative memory (no new episodic memories) - intact procedural memory (skill memory)
Dendritic spines
short outgrowths that increase the surface area available for synapses Morphology correlates with age and synaptic strength: - when immature, quite thin, small, and motile (often growing and shrinking, added and retracted, thus called plastic) - if synapse is used often, grows (thicker, larger head, or more heads) and becomes long-lasting and stable Development is the process of learning Change with age, experiences, and disease
Axon collaterals
side branches of axon May interact with other neurons' dendrites to excite or inhibit
Perilymph
similar to CSF base of hair cells bathed in this K+ moves out of soma channels into this
inner hair cells
single row of 4500 on organ of corti multiple spiral ganglion cells synapse on them (high convergence) output to 95% of auditory nerve fibers
inferior colliculi
site of synapsing (where processing occurs in smaller animals)
What happens when LGN input to striate cortex is eliminated early in fetal life?
size of V1 cortex reduced increase in size of extrastriate cortex
Tonic receptor
slow/no adaptation little or no decrease in the frequency of action potential
Why is studying olfaction difficult?
smells are complex signals and similar smelling odorants do not have physically have anything in common - difficult. to make specific ligand-gated receptor How do you create a tuning curve if multiple variables for same smell? - vary the carbon chain or side chain? - alter the concentration
Grey matter
somata
Synaptic cleft
space between axon terminal and dendritic spine 20 nm wide (too small for light microscope)
What level of processing do RGCs and LGN conduct?
spot of light or darkness in center of field Monocular no movement
Rhodopsin phototransduction
stable in dark - photoreceptors in dark are depolarized because cGMP-dependent sodium channels (CNG) are open - dark current: cations influx - cells release glutamate (hyper polarizes bipolar cells) Light splits rhodopsin into opsin and retinal --> transducin (G-protein) stimulated --> PDE activated --> cGMP broken down --> Na+ channels close --> photoreceptor hyperpolarization --> less glutamate released In dark, rhodopsin reforms
What is the result of stimulation of M1?
stimulation produces contralateral single muscle contractions AND multiple muscle movements / motor programs - latter is due to corticospinal tract axons controlling pools of motor neurons
neurochemical
substances released by one cell that produce a reaction in a target cell
chorea
sudden, rapid, jerky, purposeless movement involving limbs, trunk, or face
Acetylcholine metabolism
synthesized by choline acetyltransferase (ChAT) - marker for cholinergic neurons - presynaptic Degraded by acetylcholinesterase (AChE) - highly active enzyme in synaptic cleft - target of nerve gases and organophosphate insecticides Choline transported back into presynaptic terminal, powered by Na+ electrochemical gradient (cotransport) Countertransport to load into synaptic vesicles (allows H+ to exit)
How do gustatory receptors transmit to gustatory cortex?
taste fibers in tongue project through cranial nerves --> gustatory nuclear cells (medulla) --> ventral posterior medial nucleus (VPM) of thalamus --> primary gustatory cortex (insular cortex, deep under lateral fissure)
Catecholamine signalling
terminated by reuptake into cells, where it is reloaded in synaptic vesicles or broken down by MAO (monoamine oxidase) cocaine and amphetamines block reuptake and enhance catecholamine activity
scotopic vision
the ability to perceive visual stimuli in near darkness due to the activity of rods
Photopic vision
the ability to perceive visual stimuli under bright light conditions due to the activity of cones Fovea
Pupil
the adjustable opening in the center of the eye through which light enters diameter controlled by autonomic NS Consensual pupil size (two eyes move in parallel)
Enteric Nervous System (ENS)
the autonomic nerves in the walls of the GI tract Largely independent but responds to PSNS and SNS
endocrine system
the body's "slow" chemical communication system; a set of glands that secrete hormones into the bloodstream In CNS: hypothalamus-pituitary-adrenal glands (HPA axis)
Trichromacy Theory of Color Vision
the brain assigns a color to a stimulus by comparing the relative activity of blue, green, and red cones problem: we never see yellowish blues or reddish greens. why?
Plasticity
the brain's ability to change, especially during childhood, by reorganizing after damage or by building new pathways based on experience
dyskinesia
the distortion or impairment (difficulty) of voluntary movement such as in a tic or spasm
Memory
the encoding, storage, and retrieval of learned info the persistence of learning in a state that can be revealed at a later time evidence: recovered experiences that can be recalled
Acetylcholinesterase (AChE)
the enzyme that breaks down acetylcholine in the synaptic cleft Degrades 10000-100000 ACh molecules/sec!
columnar organization
the functional organization of the neocortex in vertical columns; the cells in each column form a mini-circuit that performs a single function
Growth cone
the growing tip of an axon or a dendrite
Agnosia
the inability to recognize familiar objects. result of damage to posterior parietal cortex
Endoderm
the inner germ layer that develops into the lining of the digestive and respiratory systems, as well as organs
saltatory conduction (mention conduction rate and AP duration)
the jumping of action potentials from node to node, moving fast through myelin and being regenerated at nodes Ensures same amplitude AP travels all along the axon typical conduction velocity = 10 m / sec -> AP duration = 2 msec
Mitral cells
the main projective output neurons in the olfactory bulbs aka second degree olfactory neurons (right after receptor cells) convergent
equilibrium potential
the membrane potential at which chemical and electrical forces are balanced for a single ion. Can be found by plugging internal and external concentrations as well as ion charge into Nernst equation For K+, EK = -80mV
Glomerulus
the organizational structure in olfactory bulb where 25000 primary olfactory neurons converge - 100-200 micrometers - 2000 glomeruli in olfactory bulb - 25000 axons terminate in the 100 micron space of a single glomerulus - 25 mitral cells per glomerulus Olfactory receptor neurons expressing same receptor protein all converge on same glomerulus Array of glomeruli makes olfactory map ABSURD precision!!!
medial geniculate nucleus
the part of the thalamus that relays auditory signals to the temporal cortex (in A1)
Synapse (definition, size, components, therapeutic use)
the point of communication between two neurons, specifically synaptic transmission (electrical-to-chemical-to-electrical transmission) Cleft is normally 20-40 nm Consists of: - Presynaptic terminal: axon terminal - Post-synaptic terminal: dendrite - Synaptic cleft: separates axon and dendrite Target of most drugs
Learning
the process by which new information is acquired by the nervous system
Histology
the study of the microscopic structure of tissues Involves fixing, or hardening, the brain through immersion in formaldehyde - once hard, can use microtome to make thin slices
Cortex (in organs, in brain, purpose and structure, how is it distinct)
the tissue forming the outer layer of an organ or structure in plant or animal In brain, thin and wrinkled to increase surface area - key to complex conceptual thinking - in brain, has about 6 laminae (outer layer is devoid of neurons in mature brain) Distinct cytoarchitecture identifies neocortex
Where are taste receptors located?
there are about 4000 papillae on tongue each contains about 200-500 taste buds each taste bud has 50-150 taste receptor cells Receptor proteins are located in the microvilli of the apical end of the taste receptor cells at the taste pore
Binocular deprivation
total activity does not predict strength of inputs to V1 - instead, it is relative activity of the 2 eye inputs Thus, binocular deprivation means neither axon population has an advantage
Mirror-drawing task (HM)
trace the star using only the mirror - HM had no memory of having been tested, but performance improves and he learns the task - results indicate that medial temporal lobe and hippocampus are not necessary for non-declarative and procedural memories Implication: multiple memory types
Transduction
transformation of a sensory stimulus energy into a cellular signal, such as a receptor potential Must encode details such as: - threshold - intensity - quantity - specificity/selectivity - frequency
Proliferative zone
transient ganglionic eminences (LGE, MGE) in the ventral telencephalon lateral ventricles
TRPM5
transient receptor potential melastatin V-modulated, Ca++ activated, monovalent cation channel that mediates a transient membrane depolarization and plays central role in taste conduction Member of the TRP cation channels superfamily - temperature sensing, inflammation, insulin secretion, capsaicin response, reduce sensing - "poly-modal" channel Structure: - subunits have 6TM domains - pore hairpin - channels are tetramer
Olfactory receptor cells
true neurons that detect airborne molecules (odorants) dissolved in mucus - have dendritic arbor, axon hillock, etc line olfactory epithelium in nasal cavity odorants bind to odorant receptor proteins on receptor cells' cilia Cells send axons through cribriform plate to form olfactory nerve that connects to olfactory bulb
Amygdala (size, locations, function, damage)
two lima bean-sized neural clusters deep in medial temporal lobe; linked to emotion (specifically fear and anger) Damage results in ablation (lack of fear and anger)
Middle ear
tympanic membrane moves ossicles (3 bones) --> move oval window --> move fluid in cochlea serves to amplify signal (large tymphanic membrane vibrations converge on small oval window attentuation reflex: lound sounds causes tensor tympani and stapedius muscle to contract --> ossicles are more rigid - function: adapting ear to loud sounds and protecting inner ear
Endolymph
unusual extracellular fluid that is high in K+ and low in Na+ apical cilia of hair cells bathed in this K+ moves from fluid through cilia tips
CALHM1
v-gated ATP permeable ion channel - unique due to size of ATP (1.4 nm) - structure similar to connexins of gap junctions, but v-gated
Human's sense of smell vs other animals
weak smellers relative to many other animals due to small surface of olfactory epithelium still impressive though
neuromuscular junction (NMJ)
when target cell of neuron is a muscle fiber Fast & reliable, large synapse, many active zones, endplate parked with receptors
Electrical synapse gap size
where gap junctions are, 3 nm - channels are in both membrane, but non-protein parts - too small to see Large enough for ATP and other cellular metabolites to pass
Spinal cord (functions, anatomy)
within vertebral column, a conduit of info both ways Part of CNS, not PNS Makeup: - attached to caudal side of brain stem - made up of grey and white matter - 31 pairs of nerves - axons exit between vertebra (2 branches) Has minimal neurons required for simple movements (such as withdrawal reflex) Damage results in paralysis (either paraplegia - legs - or quadriplegia - 4 limbs)
Apoptosis in neural development
~50% spinal motor neurons die during embryonic development Neurons are overproduced in development and excess are eliminated (undergo apoptosis) so that presynaptic and postsynaptic cells/targets match Muscle targets release neurotrophins such as NGF for which growing neurons compete (adequate supply prevents apoptosis) While too much cell death is obviously bad, too little is associated with developmental disorders like autism
Pain transmission time from toe to cortex
Αδ fiber ~ 15 m/s --> 149 ms to thalamus ~ 3 ms for thalamic synapse Total: 152 ms C fiber ~ 1 m/s --> 2.24 s to thalamus ~ 3 ms for thalamic synapse Total: ~2.24 s (synapse effect is minimal) This difference contributes to the sensation of first pain (immediate "sharp" pain) and second pain (dull ache that follows)