B&B Exam 1

2015 Exam Sample Question: A 76-year-old man with a history of prostatic hypertrophy has the recent onset of increased *difficulty urinating*. Symptoms began shortly after he started taking a *decongestant* for cold symptoms. Which of the following types of receptors is involved in these adverse effects? (A) α1-Adrenergic (B) β2-Adrenergic (C) Ganglionic nicotinic (D) Nicotinic receptor at the neuromuscular junction (E) Serotoninergic

(A) α1-Adrenergic Cold meds work on these receptors and can cause several adverse sxs. The idea here is the activation of alpha-adrenergic receptor by sympathomimetics can cause *vasoconstriction* in nasal mucosa, thus the medicine functions as a decongestant. However, alpha-adrenergic receptor stimulation can also cause contraction of the sphincter in the urinary bladder, causing *difficulty in urination*. nicotinic receptors for Ach are for muscle contraction.

2015 Exam Sample Question: A 45-year-old woman is brought to the physician because of a 4-month history of muscle fatigue. She says that she has difficulty initiating movements and focusing her eyes. Physical examination shows bilateral ptosis of the upper eyelids. Repetitive nerve stimulation testing of a motor nerve shows a 30% decrease in the compound muscle action potential amplitude. Which of the following is the most likely cause of the muscle weakness in this patient? (A) Mesothelioma of the pleura (B) Myasthenia gravis (C) Sarcoidosis (D) Small cell carcinoma of the lung (E) Squamous cell carcinoma of the esophagus

(B) Myasthenia gravis Provided in question: A CT scan of the chest is shown; the arrow indicates an abnormality.

2015 Exam Sample Question: A 30-year-old man is brought to the emergency department 30 minutes after being stung by several wasps. He is confused and has difficulty breathing. His temperature is 38°C (100.4°F), pulse is 122/min, respirations are 34/min, and blood pressure is 80/40 mm Hg. Physical examination shows dry skin and decreased capillary refill. There are multiple erythematous, inflamed marks on the back and 1+ pitting edema of the ankles. In addition to the administration of 0.9% saline, the most appropriate next step in management is administration of which of the following? (A) Atropine (B) Captopril (C) Epinephrine (D) Losartan (E) Methacholine (F) Whole blood

(C) Epinephrine

2015 Exam Sample Question: A 37-year-old woman has blurred, double vision 8 hours after eating home-preserved peppers. Six hours later, she has dysphagia, dry mouth and eyes, progressive weakness of the arms and legs, and urinary retention. She is awake and alert. Which of the following is the most likely mechanism of these adverse effects? (A) Antagonism of muscarinic receptors (B) Antagonism of nicotinic receptors (C) Inhibition of acetylcholine release (D) Inhibition of cholinesterase activity (E) Inhibition of G proteins

(C) Inhibition of acetylcholine release

How is a membrane potential value determined? RMP = ___ mV Action potential = ___ mV

(outside potential - inside potential) RMP = *-70 mV* Action potential occurs when voltage reaches *+40 mV*

"Just know this" Rexed's Laminae are basically layers of the spinal cord. You need to know two of them: 1. Substantia gelatinosa is in Rexed's Laminae # __. 2. Damage to #9 (IX) results in loss of ___ because that's where pools of ___ neurons are located.

*#2* Motor neuron pools are located at laminae #9, so damage to it would result in motor impairment. It is where alpha motor neurons (AMNs) exit the spine through the ventral horn. test Q may say: .... pathological exams indicate significant apoptosis occurs in Lamina IX cells ....

FLIP Muscular Dystrophy Note the fiber size variation due to the presence of atrophic and hypertrophic fibers, as well as increased endomysial connective tissue as part of the scarring process due to the degeneration of fibers. The crowded areas are due to the nuclei of atrophic fibers and are not inflammatory cells. Identification of the specific dystrophy type requires special stains and genetic testing. There are immunohistochemical stains for the components of this large transmembrane protein, such as dystrophin, merosin, laminin, etc. Normally, every stain will stain the sarcolemma in a linear fashion. The missing protein will not show staining, revealing what is missing.

*+++++* This is characteristic of what disease (class) hint- involves muscles fibers are all different sizes; there are blue/purple dots kind of everywhere around the fibers; fatty accumulation (white) in normal muscle, the fibers are all touching eachother and are nice and symmetrical.

+++++ Myesthenia gravis involves antibodies to ___ in NMJs. One important treatment is to inhibit ___ activation.

*Acetylcholine receptors (AChR)* on muscles in NMJs. Need to inhibit *complement* activation at NMJs (IMAGE).

What artery is the major blood supply for the spinal cord? (supplies around 2/3 on spinal cord) What a. supplies the other 1/3?

*Anterior Spinal Artery* (which is also one of the arteries from the brain lab) > around 2/3 Posterolateral Spinal a. > around 1/3 These run down the length of the spinal cord.

A young boy arrives at the clinic with dizziness, vision changes, ptosis (upper eyelid droop), and a loss in ability to move limbs (flaccid paralysis). The boy also has a wound that appears to be infected. Which neurotoxin infection does this boy likely have?

*Botulism* Key is flaccid paralysis.

Compare and contrast the mechanisms of action of tetanus and botulism toxins. Some things to conside for eachr: -How do you usually get it? -Where does the neurotoxin act?

*Botulism* Caused by C. botulinum. Can get it from foods (e.g., sausage, home-canning) or from infection of wounds (e.g., IV drug use). Infants can also be born with it -- it can colonize in the GI tract btw 5-20 weeks old. This is the most common form of botulism. Older children and adults are resistant. It releases a neurotoxin that *blocks NMJs* to *prevent muscle contraction* ==> *flaccid paralysis*. (IMAGE) *Tetanus* Caused by C. tetani. You get Tetanus when wounds are infected by spores from soil or feces. Babies can also get tetanus in their umbilical stump if mother has no tetanus antibodies. It releases a neurotoxin that binds to *motor neurons* and *inhibits GABA*, so you lose voluntary control of your muscles, but there is hyper-stimulation of motor neurons ==> *spastic paralysis*.

Diagnose: A newborn is found to *lack a cerebellar vermis*, and also has *hydrocephalus* and a large *cyst in the posterior cranial fossa*. What is the most likely birth defect / brain problem? So...... 1. Genetic lack of cerebellar vermis 2. Cyst in posterior cranial fossa 3. Hydrocephalus due to blocked drainage of 4th ventricle

*Dandy-Walker Syndrome* Genetic lack of cerebellar vermis Cyst (star in photo) in posterior cranial fossa Hydrocephalus due to blocked drainage of 4th ventricle

*+++++ "Common Test Q"* When an action potential reaches the terminal end of a neuron, it opens ___ channels so that it can flood into the neuron. i.e., What is *depolarization*? This allows what to happen during an action potential?

*Depolarization*: >> Calcium *enters* the pre-synaptic neuron at the nerve *terminal* >> *Exocytosis* of the synaptic vesicles containing neurotransmitters (and thus, release of NTs). Action potential reaches nerve terminal; triggers rapid influx of calcium, allowing the release of NTs into the synaptic cleft.

Dx this *Inflammatory Myopathy* (IM): > Subacute mm. weakness that is more *proximal* than distal. > Key/unique: *Skin changes* (*Rashes*) often presenting symptom (> half of pts). > Associated with malignancy in adults > Dx: Muscle biopsy: *Perifascicular inflammation* > Tx: Immunotherapy (Muscular disease) - so MUST overall involve mm. weakness WITHOUT sensation loss.

*Derma*tomyositis *Derma to* -- skin too Perifascicular inflammation -- in IMAGE, you can see that most of the bad (purple) stuff is on the outside of the mm. -- *peri + fascicular*. Of the 3 IMs, both Polymyositis and Dermatomyositis have PROXIMAL weakness. Inclusion Body Myositis involves weakness in finger flexion and quadriceps (raising lower legs)

Identify the two neurotransmitters involved in the physiology of ADHD. How is attentiveness influenced by the levels of these?

*Dopamine and Norepinephrine* These are catecholamines. IMAGE: x-axis is amount of catecholamines, y-axis is Prefrontal Cortex activity. > Too little catecholamines - inattention > Too many catecholamines - inattention b/c it causes feelings of stress, blocking focus. > There are ideal levels of the catecholamines where attention is optimized. So the catecholamines sort of determine how well you can focus. Dopamine release improves attention. NE helps quiet down unimportant noises.

-Name and describe the birth defect that results from a defect in *Ventral induction*. It involves a single nose and a single midline eye, and the eye is below the nose; there is only one ventricle in brain; most spontaneously abort. -Is this defect in primary neurulation, secondary neurulation, or both? -What gestational weeks would this defect occur? -Risk factor: mutation in the gene for what neurulation protein?

*Holoprosencephaly* This error in gestational brain development occurs between weeks 5 and 6 of pregnancy. Defect in *primary* neurulation only.

Compare the 2 types of post-synaptic NT receptors: Ionotropic vs Metabotropic neurotransmitter receptors in terms of: -Speed -Duration -Is the receptor itself an ion channel? -Direct or indirect effect on channel? -Second messenger involved? -Amplification? Ach has 2 receptor types -- what type of receptor is: -muscarinic AChR -nicotinic AChR

*Ionotropic receptors* are ion channels themselves. NT binds, and ions can flow through. -Fast -Relatively short duration change in ion flow -Does not involve second messengers -Direct effect on the ion channels -e.g. ACh *nicotinic* receptor *Metabotropic receptors* are GPCRs. NT binds and second messenger cascade starts. -slower than ionotropic -involve second messengers -Signal amplification occurs because a bunch of second messengers are activated at once. -e.g. ACh *muscarinic* receptor

Compare Na, Cl, and K in their permeability and how much they affect the charge/membrane potential

*K+* is the only one that actually affects the charge of the cell because it has high permeability and it *leaves faster than it enters* the cell during an action potential so there's a net movement of positve charge out of the cell *Na+* really wants to cross the membrane and influence the charge, but when the neuron is at rest, it can't really cross any because it has low permeability; it slowly trickles in *Cl-* crosses the membrane freely because it has high permeability, but it doesn't affect the charge/membrane potential because the free movement keeps a constant conc. gradient for Cl- (bc as one leaves, another goes in)

+++++ Prototypic disease in class Which NMJ Disorder is caused by *blocked calcium channels in NMJs*, preventing the muscle from receiving the signal?

*Lambert-Eaton Myasthenic Syndrome* Calcium channels blocked *Eaton up the calcium*

+++++ Name and Differentiate between the *3 levels of severity* for Autism Spectrum DO in terms of social interactions, if they speak in full sentences, effect of rituals/repetitive behaviors on daily life.

*Level 1: Requiring Support*: > Difficulty initiating social interactions - Awkward or unsuccessful reactions to others' social attempts. - Appears disinterested in social interaction. > Speaks in *full sentences* > Rituals and repetitive behaviors cause significant interference in one or more contexts > Difficulty switching between activities > For example, a person with few words of intelligible speech who rarely initiates interaction and, when he or she does, makes unusual approaches and only to meet needs only and responds to only very direct social approaches. *Level 2: Requiring Substantial Support*: > Marked impairments in social communication; impairment noticeable with support; limited social initiation; reduced or abnormal response to others' overtures; speaks in short sentences > Rituals and repetitive behaviors are *obvious* to casual observers and interfere in a variety of contexts; inflexibility of behavior; difficulty coping with change; distress and/or difficulty changing focus or action *Level 3: Requiring Very Substantial Support*: > Severe deficits in social communication; very limited social interactions; minimal response towards others; speaks in single words > Rituals and repetitive behaviors markedly interfere in all areas; extreme difficulty coping with change; great distress/difficulty changing focus or action

*+++++* "VERY High Yield for USMLE" Leptomeninges (pia and arachnoid mater), Schwann cells, chromaffin cells in the adrenal gland's medulla, and ganglia of the PNS are derived from what embryonic structure?

*Neural Crest* -- *PNS* structures *LAGS*: *L*eptomeninges: Pia mater & Arachnoid mater *A*drenal medulla (Chromaffin cells). *G*anglia: Bags of neurons outside the CNS along nerve roots/nerves or in organ walls *S*chwann Cells: Myelinate axons of PERIPHERAL NERVES (Spinal and Cranial nerves)

What is the purpose of the refracory periods in action potential directionality? Define these action potential directional terms: -orthodromic conduction -antidromic conduction

*Orthodromic conduction* - The normal conduction direction for an AP, from the soma to the terminal end of the axon. *Antidromic conduction* is the opposite, moving from the terminal toward the soma, is antidromic conduction. While nerve fibers conduct equally well in either direction, because the AP is normally initiated at the axon hillock, conduction is normally only orthodromic.

+++++ - "This is the classic, prototypic IM" Dx this *Inflammatory Myopathy* (IM): > Key characteristic: *Muscle weakness* that is more *Proximal* than distal, and is both *Bilateral*, and *Symmetrical* (same on both sides). > Diagnosis criteria: Muscle Biopsy reveals *endomysial inflammation*. (Lymphocytes seen in bx of endomysium) > Treated with Immunosuppression, namely Prednisone, Methotrexate, or Azathioprine (makes sense -- suppress immune system to bring down inflammation). (Muscular disease) - so MUST overall involve mm. weakness WITHOUT sensation loss.

*Polymyositis* Appearance of Endomysial Inflammation in a muscle bx: > (IMAGE) > lymphocytes / inflammatory cells (purple) filling up the white cracks and surrounding mm. cells.

*Neurotransmitter synthesis* -- Define: -*terminal synthesis* vs. *somatic synthesis* >> what types of NTs are made by each (not hard -- just one type made via somatic synthesis) -autoreceptors as a mechanism of inhibition

*Soma*tic synthesis -- in the soma (cell body)

Flow of CSF through brain

*choroid plexus* > *lateral ventricles* > *3rd ventricles* > *cerebral aqueduct* > *4th ventricles* > *subarachnoid space* > brain > *arachnoid villi*

+++++ What type of sensory receptors on mm. are activated when we initiate a stretch *reflex*, such as the knee jerk reflex?

*muscle spindles* muscle spindles are the muscle receptors buried inside the belly of skeletal muscle mass.

FLIP Adrenomyeloneuropathy (AML)

+++++ Name the spinal cord disease in this picture

+++++ The *Phrenic Nucleus* (nucleus of the phrenic nerve) is located at what vertebral levels? What about the *Accessory Motor Nucleus*?

- Accessory Motor Nucleus: C1-C5 (entire cervical region) - Phrenic nucleus: C3-C5 ^ The phrenic nerve, which controls the diaphragm, originates at C3-C5.

Friedreich ataxia: -caused by what genetic abnormality? (general) -caused by free radical damage to what two spinal pathways, leading to what primary sxs? -Presents with when

- Hereditary and degenerative spinal cord disease - Caused by GAA *repeats*. - Usual onset before 10 yo (may be later) -Main 2 Presentations and causes: 1. Damage to *spinocerebellar tracts* ==> pt staggers and falls. 2. Damage to *dorsal column* ==> loss of vibratory sense, proprioception. - Phenotype: > Ataxia > Dysarthria > Loss of proprioception > Areflexia with Babinski sign > Optic atrophy > Kyphoscoliosis & pes cavus > Diabetes mellitus > Cardiomyopathy > Fatal

+++++ What do each of these develop into and what type of neurulation (primary/secondary) forms them? -Neural Crest -Caudal Mass -Neural Tube +++++ Differentiate between the neural crest and neural tube in terms of what they develop into. +++++ What gestational day does each of these close? - *Anterior* (Rostral) neuropore: DAY ___. - *Posterior* (Caudal) neuropore: DAY ___.

- The Neural TUBE forms the Central NS -- brain, brainstem, spinal cord C1-S1, and both spinal and cranial nerves. There is a rostral and a caudal part of the neural tube which form different things listed before (separate card). >> Formed during *primary neurulation*. - The Neural CREST forms the Peripheral NS, mainly ganglia. >> Formed during *primary neurulation*. - The Caudal Mass forms spinal cord segments S2 and down to the coccyx (so it forms just some of the bottom part of the spinal cord). >> Formed during *secondary neurulation*. CLOSING DAYS: - *Anterior* (Rostral) neuropore: DAY 25. - *Posterior* (Caudal) neuropore: DAY 27-28. ^ If these do not close on the correct days, you get NT defects.

+++++ Define: *Somatotopic arrangement*; relative to the Dorsal Column. Where does sensory information originating from each region of the vertebral column travel in the spinal cord?

- The dorsal column has a somatotopic arrangement, meaning that a signal from a very specific location on the body travels up a very specific part of it. - called "somatotopic organization". - this kind of somatotopic organization occurs throughout the CNS

+++++ Pain fibers in the periphery: -*Ad* fibers -*C* fibers From here, the signal enters the spinal cord's ___ tract, and then the ___ __ tract.

-*Ad* fibers carry sharp, sudden pain; are faster -*C* fibers carry dull pain; are slower From here, the pain signal enters the spinal cord at *Lissauer's tract* and then goes to the *Spinothalamic tract*.

+++++ -What enzyme catalyzes the rate-limiting step of catecholamine (N,E,D) synthesis? -Structural feature of catecholamines to know

-*Tyrosine Hydroxylase* -*2* OH's on a benzene ring.

++++++ *Dorsal Column-Medial Lemniscus Pathway*: -carries what 3 signals -What are the two parts of the spinal cord that are members of this? Each carries information from which vertebral level regions? ^ So you should know which nerve the DCMLP will use depending on where the signal originates.

-2 point touch discrimination, touch, vibration, texture (stereognosis), proprioception -Fasc. Gracilis - T6 or below -Fasc. Cuneatus - T6 or above -Runs all the way up the spinal cord via the dorsal column; then crosses to opposite side of the brain; then travels up the medial lemniscus to the thalamus --> sensory cortex. -so the information is processed on the *contralateral* side.

Muscular Disease: *Dystrophinopathies (Duchenne & Becker Muscular Dystrophies)*: -In general, Muscle Dystrophy is characterized by a decrease in *Dystrophin*, which *is/does what?* -Which of the two muscular dystrophies is being described: *"___ Muscular Dystrophy"* 1) Onset in teens; before the age of 20 Delayed motor milestones; Gower's Sign Loss of ambulation by teens Life expectancy < 20-y.o., Die of respiratory failure, cardiac disease. 2) Later onset of symptoms (teens to adulthood) Preserved walking into adulthood Most live into 30's. Relative dystrophin levels in each.

-Background: Muscular Dystrophy (MD) = a group of hereditary diseases characterized by degeneration of muscle and weakness. -Both MDs are X-linked; so mostly boys. -Of course, both of these conditions would result in delayed motor reflexes since they don't have the muscle to do things. Think about stuff logically like that. -Decrease in *Dystrophin* -- Dystrophin is the largest protein in the body; it is a transmembrane protein that connects the cytoskeletons of muscle fibers to the surrounding extracellular matrix through the cell membrane. Basically, it is called *scaffolding* because it *holds muscles together* -- without it, muscles kind of just fall apart ==> Muscular Dystrophy. -Name the disease: 1) *Duchenne Muscular Dystrophy* > earlier onset and earlier death (both before 20's; teens) > delayed motor reflex milestones > lose ambulation by teenage years. ^ loss of walking is because leg muscles have just fallen apart; no dystrophin. 2) *Becker Muscular Dystrophy* > slightly later onset & death (30's) > lose ambulation during adulthood. -Dystrophin levels are the lowest in Duchenne MD; Becker MD has about half of it gone which is still bad but not AS bad. See IMAGE.

Unique appearances of each of the vertebral cross-sections: -Cervical -Thoracic -Lumbar -Sacral Mnemonics

-Cervical is wide, like a sideways oval. Very wide H-shape inside. >> C1 looks like a bunny (other quizlet set) -Thoracic is the skinny butterfly. It is quite circular. -Lumbar is the normal butterfly. It is also quite circular. -Sacral is the fat butterfly. It is quite small. It looks like someone sat on top of it.

FLIP -Dx: *A- early denervation* -This is *small group* atrophy, with small angular fibers, all indicating early denervation. -stars: Small Angular Fibers // a.k.a. Small groups of angulated atrophic fibers. -- These are muscle fibers that seem to be squished down. As also indicated in the diagram, when a fiber looses its innervation, it becomes atrophic and assumes an angulated atrophic appearance with concave contours due to the pressure of the surrounding fibers. Angulated atrophic fibers may be single or in small groups.

-Diagnosis? -- denervation of which of the classes: a) early denervation b) chronic denervation c) late denervation -Large or small group atrophy? The stars indicate *___ ___ fibers*, diagnostic for this type of denervation.

FLIP *B* - chronic denervation Because you can see *fiber-type grouping* -- dark with dark and light with light When the intact nerve fibers sprout to reinnervate the denervated myofibers, those myofibers switch to the type of that new nerve. This results in the loss of the normal chekerboard appearance on ATPase reactions. Now, large groups have same fiber type, alternating with other large groups. This is called fiber type grouping.

-Diagnosis? -- denervation of which of the following denervation phases: a) early denervation b) chronic denervation c) late denervation Key thing to note here -- has to do with grouping

Extrafusal muscle fibers are innervated by ___ motor neurons. Intrafusal muscle fibers are innervated by ___ motor neurons.

-Extrafusal: alpha motor neurons > normal skeletal muscle fibers that are innervated by alpha motor neurons and generate tension by contracting, allowing muscle movement. -Intrafusal: gamma motor neurons > Intrafusal fibers = the muscle spindle; they send sensory information about a muscle's stretch status AND receive information from gamma motor neurons.

+++++ Which Fasc. nerve will a touch, vibration, 2-point discrimination, or proprioception signal take if it originates: -T6 or above -T6 or below

-Fasc. cuneatus -Fasc. gracillis The lower spinal cord at, L3 for example, does not have FC. It only has FG. FC starts at T6. At the top of the spinal cord, like in the cervical region, both FC and FG are present.

+++++ The lateral walls of the neural tube have *3 layers* that become important brain structures: the Ventricular layer, the Mantle layer, and the Marginal layer. -*___ ___ Cells* evolve into our neurons. -which layer is innermost, outermost, and in the middle? -the ventricular layer produces what 3 future brain structures? -the *mantle* layer produces the grey matter of the ___ and ___. -the *marginal* layer produces the grey matter of the ___.

-From in to out: ventricular, mantle, marginal. -*Radial Glial Cells* are the original cells in the ventricular layer that branch out to the other layers and result in the production of all of our neurons. - The *Ventricular Layer* of the neural tube lateral walls: > is the innermost layer; close to the neurocoele. > contains: *NEG* 1) *Neuroblasts* - future NEURONS, like all of our neurons) 2) *Ependyma* - future ventricles, aqueduct, & central canal ^ *Ependyma lines the brain's ventricles* 3) *Glioblasts* - future MACROglia. - The *Mantle Layer* of the neural tube lateral walls: > is the middle layer > forms the grey matter of both the *brainstem* and *spinal cord* (H-shaped grey matter in spinal cord). - The *Marginal Layer* of the neural tube lateral walls: > is the outermost layer > becomes grey matter in the *cerebral cortex*. -- outermost in both Important: Grey matter of brain comes from mantle layer, and the grey matter of the brainstem and spinal cord comes from the marginal layer.

Microscope: Centronuclear myopathy

-Literally the name describes the image -This is a congenital myopathy (from birth) -There is one central nucleus uniformly in essentially every fiber. Some appear like they don't have a central nucleus, because the section did not pass through the nucleus. -Note that these are congenital myopathies and the specimens are from children, whose myofibers are smaller and rounder, compared to the adult muscle we are used to seeing by now.

Functional Neurons: SENSORY -- where in the brain is each neuron located? -primary, secondary, and tertiary MOTOR -- location of: 1) Pyramidal neurons 2) Alpha motor neurons 3) Purkinje neurons (*MNEM*) 4) Preganglionic Autonomic

-Sensory: primary neuron is in the sensory ganglia, secondary is in the spinal cord, and tertiary is in the thalamus. From there, it is sent to the brain. -Motor: 1) cerebral cortex 2) Brainstem & Spinal Cord 3) Cerebellum -- Purkinje neurons look like trees -- mnem: *PurkinTREE* neurons. 4) Brainstem & Spinal Cord

What 4 important neurotransmitters (and excit or inhib?) are involved in *Myotoatic Reflex* responses? (Hint: These are motor/muscle responses so they involve NMJs, and they require NTs that can either excite or inhibit.) 3 in spinal cord; only 1 NT present in the NMJ

-Spinal Cord - *GGG*; *Glutamate Excitate* > Glutamate - excitatory > Glycine - inhibitory > GABA - inhibitory -Neuromuscular junction (NMJ) > Acetylcholine - excitatory Inhibitory NTs are used in reflexes to inhibit antagonistic muscles, while the target muscle is excited.

*Urogenital Reflexes*: -these test for functioning of what region of the spinal cord (particularly, tests for lesions in the ___ ___). Two main reflexes: *A and B* 1. Anal wink 2. Bulbocavernosus reflex

-The *Sacral* region, specifically, the *conus medullaris* (the very end of the SC, before it becomes the cauda equina). -2 main reflexes: 1) Anal Wink -- stimulate skin around anus and it will wink at ya! 2) Bulbocavernosus Reflex -- grab the glans penis and the anal sphincter contracts. "If a person has a sacral lesion, you're not going to see these. These reflexes will be absent."

*+++++* *Amyotrophic Lateral Sclerosis (ALS)*: -*often associated with what genetic mutation?* -- especially if combined with dementia. +++++ -what element of of the peripheral NS is at fault? -mm. weakness pattern/progression/directionality -UMN and LMN signs/sxs

-can be associated with Fronto-temporal Dementia -- *TDP-43 mutation* -The motor neurons, coming out of the ventral horn, are affected. -characterized by gradually increasing weakness in a extremity, starting at the distal part of that extremity. -Mix of both UMN and LMN signs: weakness, atrophy, fasciculations (tongue), brisk reflexes difficulty with speech/swallowing, shortness of breath

+++++ *Spinothalamic Tract* (part of *Anterolateral* system) -carries __ and __ information -starts where and ends where? -when does it decassate (cross to contralateral side)? -receives signal from ___ tract in the spinal cord, which is where the signal enters the spinal cord. -what are the primary, secondary, and tertiary neurons in this pathway?

-carries *pain and temperature* information -starts in the spine, ends in the thalamus, because *the thalamus just needs to sort through all that pain* (mnem). -it decassates immediately after entering spinal cord. -Signal from peripheral nerve enters cord at *Lissauer's tract*, and then hops onto the spinothalamic tract in the *substantia gelatinosa*

The parts of spinal cord cross sections that control muscle: -flexion -extension What about control of more proximal vs more distal parts of the muscle?

-flexion -- dorsal part -entension -- ventral part Proximal is controlled by the more medial parts of the spinal cord Distal muscles are controlled by more lateral parts of the cord. That makes sense, spatially.

Purkinje neurons: -location -appearance -if damaged, you get ___ and ___. Pyramidal cells -- location; what happens if damaged.

-largest neurons in the cerebellum -branch/tree like in appearance -if damaged, you get *ataxia* and intention *tremors*

*Polyneuropathies*: -The problem is with which element of the peripheral NS? -Involves weakness in primarily proximal or distal aspects of limbs? -LMN signs -There are *TWO* types: acute and chronic. We are interested in the acute polyneuropathy, which is ___ ___ ___. -They are diagnosed using *WHAT METHOD*?

-problem is with the peripheral nerves -- the signals do not get across the peripheral nerve. why might signals be slowed down or stopped? In GBS (below), the peripheral nerves are demyelinated. > (as opposed to muscles or NMJs) *Poly-* because it affects multiple muscles in multiple regions. -Guillain-Barre Syndrome (GBS) > acute polyneuropathy > there are others, but we care about this one. > Here, *demyelination* of peripheral nerves is what slows them down. *Nerve Conduction Studies* determine the pathologies of polyneuropathies -- you measure the speed of a signal traveling down an axon.

An action potential starts at the __ __ of a neuron How are action potentials propogated from one neuron to another? Involves ___ channels.

-starts at Axon Hillock -Na+ channels possess two gates: an activation/ deactivation gate and an inactivation/deinactivation gate. -Overall, the signals keep dying out as they travel through an axon and then get re-excited at the next Node of Ranvier. Signal is initiated at the axon hillock when depolarization activates Voltage-Gated Na+ channels, and *Na+ ions flow into the axon*. -But these can travel only a few mm *because the resistance of the axoplasm is large compared to their energy* and *results in resistance that slows down the signal*. -Na+ channels at the next node must be depolarized to threshold to initiate another action potential to carry the signal farther. This process in repeated at each node along the axon. -Ion concentrations are set up such that Na+ ions would be driven INTO the neuron along both their electrical and concentration gradients if there were openings in the membrane. -This influx of Na+ ions causes the rising phase of the AP and the membrane potential peaks at about +40 mV, but the sodium channels do not stay open long enough for the membrane potential to attain the equilibrium potential for Na+ (+60 mV) - These channels close after a brief time by a process called inactivation. - The membrane potential must return below threshold for Na+ channels to deactivate and then deinactivate to be ready to activate again.

Basic Structure of a chemical (NT) synapse: Pre-synaptic neuron: -What things carry NTs down towards the synapse in a neuron? -Place where NTs collect before release Synapse: -Enzymes present Post-synaptic neuron: -NT receptors are concentrated in the ___ ___.

-synaptic vessicles -presynaptic membrane/density/active site -degradative enzymes break down NTs -postsynaptic membrane/density

-GABA and Glycine are excitatory or inhibitory? -This is because it causes __polarization of the neuron. -What element influxes or effluxes when: >> GABA binds to GABAa receptor >> GABA binds to GABAb receptor >> Glycine binds its receptor

-they are the 2 primary *inhibtory* molecules -*hyper*polarization = inhibitory (and excitatory is depolarization) -see IMAGE -- red font

Change in names of a motor nerve from brain to muscle: Starts as a cell body in the brain (grey matter) What is a tract? what kind of matter? What is a lower motor neuron / alpha motor neuron? What is a motor unit? __ + __ Define *Terminal Arborization* (n.) -- think about the name

-tract: bundle of axons (WHITE MATTER) that travels down spinal cord. -alpha/lower motor neuron: efferent neuron of the PNS that connects the CNS with the muscle to be innervated. -motor unit: LMN + the muscle CELL -terminal arborization- the end of an axon branches into these, which reach out to the muscle cells.

-precursor for serotonin -precursor for histamine

-tryptophan -histidine

What type of motor neurons are: -Pyramidal neurons -Alpha motor neurons (upper vs. lower motor neurons -- in brain or brainstem/spinal cord?)

-upper motor neurons -lower motor neurons -- they're in the ventral horn of the spinal cord. They form a motor unit with the muscle they innervate. They look like little eyeballs under a microscope.

2 types of gated channels: Electric channel vs chemical channel

1) Electrically/voltage-gated channel: electric signal used to open channel 2) Chemical channel: chemical/ligand binds to channel to cause conformation change so that other stuff can come through

Quiz: True of False 1) Glu is an inhibitory neurotransmitter 2) GABA is an inhibitory neurotranmitter 3) ACh is an excitatory neurotransmitter 4) Gly is an inhibitory neurotransmitter 5) Activation of an ionotroic receptor always causes excitation 6) Activation of a metabotropic receptor always causes excitation

1) F 2) T 3) Ach can be either excit. or inhib. 4) T 5) F 6) F

Name these other infantile reflex: 1) Sudden loss of support -> extension, then flexion, of UEs 2) Fencing posture with neck rotation 3) Adduction of opposite leg (scissoring) 4) Baby held in standing position is able to support self & step 5) baby held horizontal & prone -> extends neck & arches back 6) Simulated falling -> extension of arms

1) Moro 2) Tonic neck reflex (IMAGE) 3) Crossed adductor reflex (IMAGE) 4) Supporting reflex 5) Landau reflex (IMAGE) 6) Parachute reflex (IMAGE)

-*Peptide* neurotransmitters are different from the other classical NTs due to these unique characteristics: 1) They are synthesized from ___. 2) How do they turn from *inactive to active* NTs? 3) Made in the ___ of the neuron, as opposed to classical NTs which are made where? -Why are peptide NTs termed *neuromodulators*?

1) mRNA -- b/c they are peptides/proteins 2) Exist in an *inactive* state at first, and are eventually cleaved by peptidases into the *active* form. 3) Peptide NTs are made in the *cell body* of the neuron, and then transported down to the terminal to be released. Classical NTs are made at the terminal. -Some Peptide NTs are often called peptide *neuromodulators* because they modulate/affect the activity of other NTs. >> i.e., a peptide neuromodulator is packaged and released with another NT and modify the action of the other NT after release.

If a parent does not want to put their ADHD child on a stimulant or there is some other good reason to avoid stimulants, what 3 non-stimulant pharmaceuticals are often prescribed?

1. *Atomoxetine (Strattera)* norepinephrine selective reuptake inhibitor 2. *Alpha Agonists* -- clonidine and guanfacine. 3. *Anti-depressants* (NOT SSRIs) > *Wellbutrin (bupropion)* - norepinephrine, dopamine reuptake inhibitor (NDRI) > *Tricyclic antidepressants* - affect multiple neurotransmitters including NE and DA > These seem to improve all 3 major sxs of ADHD. Can be used if other treatments have not been effective, if have intolerable side effects, or if tolerance or abuse of stimulant is a problem.

*+++++* What are the 4 most important co-morbidities with ADHD.

1. *Disruptive Behavior* <== +++++ -as high as *50%*! -conduct DO, operational defiance DO -combination is disastrous ==> antisocial behaviors and depression. 2. *Anxiety* -10-40% -most common with *inattentive* type 3. *Mood disorders* -20-30% -depression (25%), bipolar 4. *Learning Disorders* - 25% - BUT as high as 80% have significant learning problems Also, an array of developmental problems - motor, cognitive, emotional, and social. These complicate the picture and increase the risk of other psychopathology.

Overall 4 places on a neuron that important common medications work at

1. Cell body / soma -can affect receptors (agonists, antagonists) -can affect second messenger signals, which can mess up: >> channels (e.g., benzos open Cl- channels at GABAa receptors), >> number of surface receptors, and/or >> gene expression 2. Axon terminal -can inhibit reuptake >> e.g., SSRIs affect Ser reuptake receptors at the terminals of axons. -can inhibit release of a NT >> e.g., Botox prevents release of Ach -can mess up degradative enzymes to increase number and lifespan of NTs. 3. Synaptic Cleft -can block extracellular degradative enzymes (prolongs effect of NT) >> e.g., *Organophosphates* (insecticides)- irreversibly inactivates acetylcholinesterase -can interfere with neuronal re-uptake of the NT (prolongs effect of NT) 4. Glia -can interfere with glial uptake metabolism of neurotransmitter

Classify *EACH* type of ADHD. "ADHD with *___ Presentation*" : 1) Pt exhibits clinically significant hyperactive, impulsive, and inattentive behaviors. 2) Pt's main issues are hyperactivity and impulsivity. 3) Pt is very inattentive, but not necessarily hyperactive.

1. Combined Presentation 2. Predominately Hyperactive-Impulsive Presentation 3. Predominantly Inattentive Presentation ^ Example vignette: • 16 y/o girl with failing grades at school • Has been doing fairly well until this school year • *No behavioral problems at home or school*, but... • Loses pens, books, homework • Difficulty getting started and organizing • Teachers complain she is "day dreaming" Often, you might see a kid with predominantly hyperactive and impulsive ADHD traits who becomes predominantly inattentive as he/she ages. ADHD usually stays with the person throughout life, but can change presentation. Hyperactivity & Impulsivity tend to decrease with age, possibly b/c the person develops compensatory strategies (CS's). Inattentiveness tends to stick, but you can still develop CS's.

Higher on inside or outside? 1. Na+ 2. Cl- 3. K+

1. Outside 2. Outside 3. Inside Mnem: Na and Cl want to be together, like with table salt --- these are higher in concentration outside of the cell (extracellular space). Mnem: *K*in --- K+ is the only one that's higher inside the neuron. It likes to stay inside the cell. K+ sticks to its own kind/its *kin* (K+ only hangs with K+).

*+++++* Identify the following potentials as NP = non-propagated or P = propagated. A. Nerve action B. Inhibitory post-synaptic C. Receptor D. Motor end plate E. Excitatory post-synaptic

A = P B = NP C = NP (receptor potential is at nerve ending associated with a sensory receptor; it may depolarize the nerve fiber to threshold) D = NP (motor end plate potential is synaptic potential in skeletal muscle fiber membrane) E = NP

Fiber types A,B,C -- relative sizes and velocities of conductance Somatosensory receptors send the info through Aβ, Aδ and C. Out of these three: -Which one has the slowest speed? -Pain is transmitted by which two fiber types?

A > B > C

For Na gated channels, define: Activation Inactivation Deactivation Deinactivation and in what order do they occur?

AG = Activation Gate IG = Inactivation Gate >> The four terms are defined by what happens to these. • *Activation*: AG opens (Na+ enters) • *Inactivation*: IG closes • *Deactivation*: AG closes • *Deinactivation*: IG reopens (ready for another AP). >> With the activation gate closed and the inactivation gate open, the Na+ channel is once again in its deactivated state, and is ready to participate in another action potential. Wikipedia: • *Activation* is the opening of Na+ gates. • *Deactivation* is the closing of Na+ gates, exact opposite of activation. • *Inactivation* occurs once the action potential reaches its peak. The peak/maximum voltage is when enough Na+ has entered the neuron and the membrane's potential has become high enough, the Na+ channels *inactivate* themselves by closing their inactivation gates. • *Deinactivation*: When the membrane's voltage becomes low enough, the inactivation gate reopens in a process called deinactivation.

What is the difference between *absolute* and *relative* refractory periods in action potentials? When does each occur? When does the *subnormal phase* occur? Relate these to the states of both Na+ and K+ channels.

Absolute- during the peak of the AP; it is not possible to have another AP at this time. *CHANNELS*: => Na+ gates close faster than K+ gates. => In most of these periods/phases, as you can see in the IMAGE text, the K+ channels are open.

*Guillain-Barre Syndrome (GBS)*: -what type of disease / what is the cause? -motor and sensory presentations -It is diagnosed with *what type of study?* -Lumbar puncture: High or Low *WBC* and *protein* levels? -In the affected mm., GBS pts may experience: >> *what motor sxs*, with muscles and reflexes? >> loss of *what sensory perceptions*? >> *proximal or distal* loss of sensation?

Acute-- sxs come on suddenly; works its way up. -caused by *demyelination* of the *peripheral nerves* themselves; it is a *polyneuropathy*, so multiple nerves are affected. -Motor: *LMN* weaknesses -- slow eye movements; slow movements in general; really have to put effort into it. -Sensory: *DISTAL* sensory loss of vibration/proprioception AND pain/temperateure (so ALL senses) -as you go more proximal, they can feel more (makes sense -- think of it as impulses being more likely to die out the further they travel) -Physical exam: symmetric weakness, areflexia, sensory loss -Diagnosed with a *Nerve Conduction Study* -- measures the speed of a signal traveling down an axon.

-Define: Electrotonic potential -What are the 2 types of electrotonic impulses, both of which occur at ALL sensory receptors?

All responses, whether de- or hyperpolarizing, that do not move the membrane potential to threshold are called *electrotonic potentials*. They are not propagated, and die out very quickly. The 2 types of electrotonic potentials, which occur at ALL sensory receptors (*receptor potentials*) are the excitatory (*EPSP*) and inhibitory (*IPSP*) post-synaptic potentials.

++++++++++++ "This EM is testable" EM of a axodendritic chemical synapse with parts labeled. Include Synaptic vessicles (carrying NTs), microtubules, presynaptic button, dendrite of post-synaptic cell; be able to tell which is pre- and post-synaptic.

And the axodendritic synapse is where the two meet.

The part of the spinal cord where pretty much all spinal tract axons cross from one side to the other is the ___ ___ ___. A lesion in this area, called *___*, is likely to cause what characteristic finding?

Anterior White Commissure Presence of a lesion in the AWC is called *Syringomyelia * ==> sxs are Loss of pain and temperature sensation on both sides. Mechanism: Pain and temperature are unable to cross to the other side. Depending on where it starts, you can estimate where the lesion is.

How to tell the left from the right side of a vertebral cross section? IMPORTANT

Any time anyhting involves "left" or "right" anything, be sure to read the L and R labels provided in the image.

How are the intensity, velocity, and duration of stimuli determined (e.g., pain from a cut)?

As the stimulus intensity increases: Each sensory receptor's firing frequency increases More receptors will fire

A 52-year-old man has been losing feeling in his extremities for the past 18 months. Especially noticeable is loss of light touch, pressure and vibration sensations. After conduction velocity testing of sensory nerve fibers, which nerve fiber group should have a decreased conduction velocity and, thus, corroborate the patient's complaint. A. A-alpha B. A-Beta C. A-gamma D. A-delta (Ad fibers) E. C fibers

B. A-Beta -- (sensory nerve fibers, no A-alphas) A-alpha nerve fibers carry information related to proprioception (muscle sense). A-beta nerve fibers carry information related to touch. A-delta (Ad) nerve fibers carry information related to pain and temperature. C-nerve fibers carry information related to pain, temperature and itch.

+++++ "This has SIGNIFICANT clinical importance." A bolus of *K*Cl was accidently given intravenously to a patient which increased the extracellular concentration of *K+* by a factor of 5 times in a short time. This can affect heart muscle cells and neurons by causing which of the following? A. Hyperpolarization B. Depolarization C. No effect > This is NOT intuitive, so don't think about the behavior of K+. We only know this fact because of Nernst Equation calculation. Define *depolarization block* and *hyperpolarization block* (This is the method we use for neuron and nerve blocking.)

B. Depolarization A sudden, large increase in extracellular K+ will depolarize neurons (and muscle cells). If neurons are put into *depolarization block* and remain there death will ensue. Depolarization block: blocking of nerve due to depolarization: A neuron cannot produce any more APs if it remains depolarized -- If the MP remains high, above the threshold, the neuron is considered to be in a *depolarization block*. So essentially, you can block the activity of a neuron by keeping it depolarized, preventing it from reaching a state where another AP can occur. Hyperpolarization block: blocking of a nerve due to hyperpolarization: If, instead, the MP is maintained below the RP level, the neuron is considered to be in hyperpolarization block. > e.g., REM sleep paralysis: This occurs by normal inhibitory synaptic activity on spinal and brainstem motor neurons (except for CN III allowing for rapid eye movements) during the REM phase of sleep to prevent acting out of dreams. If one awakens directly from REM, the lingering effects of "sleep paralysis" may be experienced for a period of minutes.

Derek is a 30-year-old man who was diagnosed with Intellectual Disability when he was a child. He is currently working at a job that requires little conceptual skills or interactions with others. He is able to care for his personal needs and participates in household tasks, though it took considerable time and repetition for him to learn these skills. He does not require constant supervision. What Intellectual Disability severity level is Derek exhibiting? A. Mild B. Moderate C. Severe D. Profound E. Needing Very Substantial Support

B. Moderate Moderate >> Mild because it clearly takes him a really long time to perform basic tasks.

Sample Test Question: GABAergic inhibitors: A. Includes activation of GABAa receptors which increase K+ ion outflow. B. Includes activation of GABAb receptors which increase Cl- ion inflow. C. Includes activation of GABAa receptors which increase Cl- inflow. D. Includes activation of GABAb receptors which increase Na+ ion inflow. E. Is secondary to the activation of aN NMDA receptor.

C. Includes activation of GABAa receptors which increase Cl- inflow.

*+++++* Tetradotoxin is an agent that blocks which of the following channels? A. Voltage-gated Ca++ B. Voltage-gated K+ C. Voltage-gated Na+ D. Ligand-gated Na+ E. Ligand-gated K+

C. Voltage-gated Na+

A graded potential, such as an EPSP A. can travel the length of the tibial nerve B. is dependent on Ca++ for propagation C. dissipates within a few millimeters D. depends on a neurotransmitter for its propagation

C. dissipates within a few millimeters (electrotonic potentials do this)

+++++ Anterior and Posterior *Neuropores* (High Yield) : -Give the numbers of the gestational days on which the rostral and caudal neuropores close. -Tell what protein is elevated in maternal serum when neuropores fail to close (Neural Tube Defects). -Then name a vitamin women can take to prevent faulty closure, and tell when the vitamin must be taken.

CLOSING DAYS: *Anterior* (rostral) neuropore: DAY 25. *Posterior* (caudal) neuropore: DAY 27-28. ^ If these do not close on the correct days, you get NEURAL TUBE DEFECT ELEVATES: 1) *AFP* (Alpha fetoprotein) 2) *AChE* (Acetylcholinesterase) A positive result of these indicates a neural tube defect, caused by closure failures in one or both of the 2 neuropores (anterior & posterior). Pregnant women should take *Folic acid* (B9) if they are expecting.

Pathway of *Dorsal Spinocerebellar tract* -does it cross sides? -How many neurons total? -What is the *nucleus dorsalis*? -enters the cerebellum at which peduncle? -type of info it carries and for what vertebral levels?

Dorsal column to dorsal spinocerebellar tract to *Inferior Cerebellar Peduncle* to *ipsilateral* cerebellum. Does NOT cross sides -- ipsilateral. At the T1 level, synapses at the *Nucleus Dorsalis* then straight to inferior colliculus. So it only has *two* neurons -- primary and secondary. Remember, the *nucleus dorsalis* is the circular shape in the spinal cord cross sections. touch, pressure T1 and below (so everything except the cervical vert.).

FLIP Duchenne Myodystrophy These boys are normal at birth, but walking is often delayed. They cannot keep up with their peers as time goes by. Usually, pelvic girdle and shoulder girdle muscles are initially involved. There is muscle atrophy, but the legs appear hypertrophic due to increased fibrofatty tissue in the degenerating muscle, called pseudohypertrophy.

Dx

A 45-year-old man with a history of a stroke comes to the physician for a follow-up examination. Physical examination shows hyperreflexia of the patellar tendon tap. The spasticity reflects loss of inhibitory influences that normally limit responses to afferent signals that convey information about muscle stretch. Which of the following structures within the muscle actively *initiates* the abnormally brisk patellar *reflex arc* in this patient? A. Alpha motor neurons B. Extrafusal fibers C. Gamma motor neurons D. Golgi tendon organs E. Spindle afferents

E. Spindle afferents

The hormones secreted by the adrenal mass are derived from which of the following amino acids? A. Arginine B. Glutamate C. Glycine D. Tryptophan E. Tyrosine

E. Tyrosine tyrosine is the precursor for DEN: dop, *epi*, and norepi. Epi is made by adrenal glands.

The Neurocoele develops into what 5 brain structures (hint: all 5 contain ___) MNEM: *FLATS*

Everything that holds CSF is made from the neurocoele. MNEM: *FLATS* Fourth ventrical Lateral Ventricals Aqueduct Third Ventrical Spinal cord's central canal. L.O.: know the neurocoele derivatives that contain cerebrospinal fluid in the adult.

Which of the following has a quick onset of action? 1. GABAa 2. GABAb

GABAa has a quicker onset because it is ionotropic. GABAb is metabotropic.

Interneurons -most are stimulatory or inhibitory? -Thus their NTs are mostly ___ and ___.

GLYCINE (spinal cord) GABA (brain)

Primary, Secondary, and Tertiary neurons -- in general, where is each usually located in any of the sensory pathways. This is helpful -- a general rule about these types of neurons. Use dorsal column as example.

In the dorsal column: The PRIMARY NEURON goes from the peripheral receptor to the spinal cord, all the way up the spinal cord, and then synapses with the secondary neuron in the medulla/ brainstem. The SECONDARY NEURON decussates across the medulla and then ascends to the thalamus, where it synapses with the tertiary neuron. The TERTIARY NEURON starts in the thalamus and ascends up to the somatosensory cortex.

Dx this *Inflammatory Myopathy* (IM): > Key: *Does not respond to immunotherapy*, unlike the other two inflammatory myopathies. > Diagnosis: Biopsy shows *rimmed vacuoles* > Weakness of *finger flexion* & *quadriceps* (Muscular disease) - so MUST overall involve m. weakness WITHOUT sensation loss.

Inclusion Body Myositis (IBM) Immunotherapy will give them SEs with no improvement; they just need occupational and physical therapy.

*Lateral Corticospinal Tract*: -controls what? -starts where and ends where? -ipsi- or contralateral?

It controls movements of all 4 limbs and all of the digits. It is a long bundle of axons that *starts in the motor cortex* and *ends in the contralateral ventral gray horn of the spinal cord.* From the spine, the signal goes to a muscle via a spinal motor neuron. So if I want to raise my hand, or do anything with my limbs, it is done through this. Contralateral - moves a limb on the opposite side.

Outcome if the *Artery of Adamkiewicz* (which supplies blood from the aorta to *whch spinal artery*?) is blocked. It will impair the ___ part of the spinal cord. It is located *between which 2 vertebrae*? Thus it would affect *what parts of the body*?

It will impair the *Anterior Cord* ==> Anterior Cord Syndrome (*ACS*) It is located *between T12 & L1*; so blocking would mess up L1 and down areas. mnem: *A*rtery of *A*damkiewicz messes up *A*nterior part of spinal cord. Ventral/motor messups - mid thoracic and down Blood will not be able to get to the anterior part of the spinal cord in the thoracic and lumbar regions if this artery of adamkiewicz is blocked.

EM: Rod-body, or nemaline myopathy

Literally the name describes the image This is a congenital myopathy (from birth) Material similar to Z-bands accumulates into rod-shaped structures (nemaline rods).

Amyotrophic Lateral Sclerosis (ALS) -Key characteristic is *loss of both __ and __ functions.* -Damage to what part of the spinal cord? -- the ___ horn. -sxs -outcome

Loss of Both UMN and LMN (Both UPPER AND LMN SIGNS) Anterior Horn Damage (LMN loss, "Amyotrophic)" weakness, fasciculations, atrophy Lateral Corticospinal Tract Damage (UMN loss, "lateral sclerosis") ==> paresis, hyperreflexia, and spasticity, along with a Babinski sign Sensation usually is unaffected Mutation of SOD1 Outcome is death. Only tx extends life 1-3 months.

+++++ *Myasthenia Gravis* (MG) is an auto-immune disease that is caused by the person's immune system producing antibodies to _____. >> You will see this question come back again and again in one form or another in many of your future exams. <<

MG is caused by the IS's production of *Anti-Acetylcholine Receptor* antibodies (ABs against the muscles' Ach recptors in NMJs. More: > Production of this AchR antibody by the immune system results in fewer signals being sent by nerves to muscles, causing the characteristic muscle weakness Myasthenia Gravis. > *Symptoms*: mm. weakness, dropping eyelid(s), difficulty speaking, difficulty chewing, seeing double / double vision. > Make the connection: MG is caused by the IS making ABs to the Ach receptors on muscle fibers, so voluntary/somatic impulses are stopped at neuromuscular junctions. This renders Ach useless, and makes voluntary movements very difficult. > A positive AChR Ab test is a reliable test for diagnosing autoimmune myasthenia gravis (MG). It is highly specific (as high as 100%). Thus, if a person tests positive for this antibody, they have MG.

A cross section of the pons should show only what nerve? (bilateral)

Medial lemniscus nerve this is part of the dorsal column medial lemniscus pathway; by the time it gets to the pons, it's only the medial lemniscus.

2 types of CNS motor neuron chains for muscle innervation -- somatic and autonomic motor neuron chains. -Name the neuron types in each (both of these are 2-neuron chains). -Name the path in CNS sensory neuron chains (series of 3 neurons)? 2 of those have something in the PNS -- what is it? What types of neurons are in the two motor types?

Motor neurons are characterized as "upper" if they originate in the brain, and "lower" if they originate in the spinal cord. Upper motor neuron disease causes stiffness, which is called "spasticity". Lower motor neuron disease causes weakness, loss of muscle ("atrophy") and muscle twitching ("fasciculations"). Sensory: -starts at receptor (eye, skin, etc.) and travels to DRG, then up spinal cord, then to thalamus, then to brain, hopping onto a different neuron each time. -Here, the *DRG is in the PNS* Motor: 1) somatic motor: -Upper Motor Neuron in brain (motor cortex) or spinal cord -Lower Motor Neuron goes from spinal cord to muscle. -striated muscle 2) autonomic motor: -Pre-ganglionic neuron (CNS) in the spinal cord or brainstem connects to... -Post-ganglionic neuron (PNS) which connects to... -smooth muscle (imagine one coming from medulla for breathing)

*+++++* Dx the disease: > Key: *FLUCTUATING* symptoms of mm. weakness, worsen with fatigue, improve with rest. > Key: Production of antibodies to the *Ach receptor (AchR)* on muscles in *NMJs*. > Also involves the production of Abs to Muscle-specific kinase (MuSK) > Produces lifelong weakness of voluntary movements. > Could involve a thymoma, so a thymectomy might be needed. > Specific weaknesses: -Ocular (ptosis, diplopia) (eye mvmnts, chewing, etc) -Respiratory (shortness of breath) -Limb weakness

Myasthenia gravis NOTE: If sxs are there kind of all the time and don't improve with rest or anything, you are probably not dealing with MG. MG always waxes and wanes. "Typically, myasthenia gravis patients are fine in the morning (because there is large amount of acetyl choline in the synapse to overstimulate the small numbers of residual receptors), but gradually lose strength through the day, and cannot even hold their eyelids open as the day goes by."

Tyrosine is a precursor for what 3 NTs? These are collectively called ___amines.

NED -- norepi, epi, & dopa Catecholamines "catechol" because 2 OH's on benzene ring. Rate limiting step catalyzed by Tyrosine Hydroxylase

*+++++* "VERY High Yield for USMLE" What are the Big 4 Neural Crest Derivatives in the nervous system? > mnem: *LAGS* And there are 2 classifications of the meninges. Which classification, *Patch* or *Lepto* (leptomeninges or pachymeninix) do pia, dura, and arachnoid mater come from?

NERVOUS SYSTEM DERIVATIVES to know: 1) *L*eptomeninges (pia & arachnoid) 2) *A*drenal Chromaffin Cells (epinephrine) 3) *G*anglia (PNS sensory & autonomic nerve bundles) 4) *S*chwann Cells (peripheral nerve myelin) Includes all of the peripheral nerves and ganglia; = cranial nerves (except optic) and spinal nerves, as well as the nerves that branch out into the peripheral body. Leptomeninges: pia mater ("delicate mother") & arachnoid mater ("web-like mother") THIN, from both neural crest and mesoderm (lepto = delicate or thin; thus = the 2 delicate meninges) 2. Pachymeninix: dura mater ("tough mother") THICK, from mesoderm

+++++ Application of local anesthetics, such as lidocaine, blocks ___ channels on nerves, thus preventing the transmission of action potentials carrying pain signals.

Na+ channel

+++++ What disease can destroy dorsal column, making the patient show a very poor two-point discrimination?

Neural syphilis

Neuroblast migration defects (5 of them): -these occur between moths __ and __ of gestation. -brain characterized by abnormally large ___. -sxs Schizencephaly, Lissencephaly, Pachygyri, Polymicrohyri, and Heterotopias

Neuroblast migration problem by *3-5 months* gestation Abnormal gyri Genetic or other causes (e.g., stroke, drug use, etc.) Disruptions of neurotrophins Seizures, cognitive, & motor problems can be present 1. SCHIZENCEPHALY Cleft brain (lined with gray matter) Uni- or bilateral Can be with porencephaly (lined with white matter) 2. LISSENCEPHALY Smooth brain Few or no gyri 3. PACHYGYRI ("pachy" means thick) Broad (thick) gyri Fewer than normal numbers of gyri 4. POLYMICROGYRI (POLYGYRI) Too many small gyri. Many more additional gyri detected histologically 5. HETEROTOPIAS (least severe migration defect) Normal islands of tissue in wrong place

2 theories of sensation: -Pattern Theory -Specific Nerve Energies Theory

Overall, it's most accurate to describe sensation as a combination of both theories. Neither one alone accounts for all aspects of sensation. From his Word Doc: • Considerable evidence supports the theory of SPECIFIC NERVE ENERGIES THEORY, that is, receptors are highly sensitive to one specific modality of stimulus; thus, this specific modality is referred to as the ADEQUATE STIMULUS or the SPECIFIC ENERGY for that receptor. Furthermore, the same sensation is perceived whether the sensory neuron is naturally or artificially stimulated. For instance, if pressure is applied to the retina, a flash of light is perceived. • Another theory of sensation is the PATTERN THEORY. In this theory, sensation results from the pattern of input from sensory receptors that is set up in the spinal cord and/or brain stem and perceived in the cerebrum. That is, different sensations would be coded by different patterns of action potentials produced in a single sensory fiber (e.g., a touch sensation could be coded by a low frequency of action potentials and pain sensation by a higher frequency of action potentials). The number of sensory fibers similarly active is also important in establishing the pattern. This type of sensory detection system seems to be used for sensations such as tickle and pain, some of which have no specific receptors.

*+++++* There are three ways to classify neurogenic muscle atrophy, and they are phases of the disease. What can you observe in terms of the muscle fibers in each of these 3 types? Early Denervation -- specific fiber type? Chronic Denervation Late Denervation

Phases 1) Early denervation. Loss of motor units leads to: - *small angular fibers* - involvement of both fiber types Phases 2) Chronic denervation. Axonal sprouting and reinnervation leads to: - *large motor units* - *fiber types group* like oil & water Phase 3) Late denervation. Loss of large motor units leads to: - *grouped* atrophy

ADHD is associated with lower activity in what section of the brain?

Prefrontal Cortex The PFC is highly regulated by and rich in catecholamines (dop and NE)

General clues to a *musclular disease* -- problem is with the muscle itself, not a nerve or lesion. Always get *what test* (level) for these pts? <== because it is elevated when muscle breaks down.

Progressive mm. weakness w/o sensory problems. Be sure to check *Creatinine Kinase (CK)* level for these pts. Several categories. e.g., Muscular Dystrophy (MD) = a group of hereditary diseases characterized by degeneration of muscle and weakness. Some Categories: mnem: *Mmm get 'em* -- *Md GITM* 1. Muscular Dystrophies (MD) ---AND THEN the Myopathies: ---*get 'em*: *GITM* 2. Genetic myopathies (GM) 3. Inflammatory myopathies (IM) 4. Toxic myopathies (TM) 5. Metabolic myopathies (MM)

+++++ What are the three *social communication* deficits required for ASD?

Reciprocity/communication, Nonverbal communication, & Maintaining relationsips. 1. Deficits in social/emotional reciprocity -- i.e., difficulty interacting w/ and understanding others. -- Conversation is like playing ping-pong, you say things back and forth, but when talking to a person on the spectrum, that ping-pong ball is often not returned. Communication can be confusing on both ends. 2. Deficits in nonverbal communicative behaviors. -- Eye contact, gaze, gestures, facial expressions 3. Deficits in developing or maintaining social relationships -- Failure or difficulty adjusting behavior to fit social situations (e.g., yelling in a movie theatre). -- Lack of interest in other children/peers -- Lack imaginative/pretend/creative play

Basal and Alar Plates of the neural tube (NT): • They are part of the __ layer of the the (rostral or caudal) neural tube? • They are separated by the ___ ___. • *Which grey horn does each develop into?* • Be able to point out each in a spinal cord cross section.

Remember, the mantle layer forms the grey matter of the brain and spinal cord. • The Basal and Alar plates are sections of the *mantle layer* of the *caudal* neural tube. • They are separated by the *Sulcus Limitans* • The basal plate forms the *ventral grey horn* of the spinal cord, which carries motor information. The more midline part of this plate has a protrusion and that section controls autonomic (involuntary, smooth muscle) motor signals.

Microscope image: *Inclusion body myositis (IBM)* -- the *Peter Frampton* disease. -what to not about pathology -clinical presentation

Rimmed vacuole (with faint blue dots) clinical presentation: steroid resistance

+++++ The *preganglionic parasympathetic nerves* exit at what vertebral level range?

S2-S4

How does each of these proteins influence the organization/development of the neural tube during embryonic development? And from what part of the neural tube is each one made? -Bone morphogenetic protein (BMP) -Sonic hedge hog (SHH) protein (MNEM)

See diagram in IMAGE. Here's the rule: *BDSM* -*B*MP leads to production of *D*orsal/sensory neurons. *S*HH leads to production of ventral/*M*otor neurons. 1. *Bone morphogenetic protein (BMP)* > Normally induces ectoderm to become EPIDERMIS of skin. > Influences the dorsal neural tube to form our dorsal (sensory) neurons. > BMP can be shut off, which allows SHH to be made. 2. SHH is produced by: a) Neural tube *floor*-plate cells, and b) the Notochord -As a result of SHH, the neural tube develops ventral patterns that become ventral (motor) nerves. Like sonic the hedgehog is always running -- motor neurons.

+++++ What is the pathway of a touch/vibration/proprioception/texture signal or a 2-point discrimination signal coming up the *Dorsal Column-Medial Lemniscus Pathway*? Where does it decassate (cross sides)? Via the __ __ fiber. What are the 3 main nerves used in the pathway (i.e., the pathways primary, secondary, and tertiary neurons)? "Yes, the Dorsal Column-Medial Lemniscus Pathway is always on the test."

Signal travels up *Dorsal Column* nerve (primary neuron) in the spinal cord to reach its nucleus in the *medulla*. This is its first synapse. Its nucleus is the Dorsal Column nucleus. Then *it decassates, moving to the opposite side* via the *internal arcuate fiber*. Now it travels up the *Medial Lemniscus* nerve (second. neuron) on the opposite side of the original stimulus to reach the thalamus, where it travels up the *Internal Capsule* (tert. neuron) sensory cortex. Overall pathway: receptor => dorsal column => nucleus of either FC or FG in medulla => internal arcuate fibers => medial lemniscus => pons => VPL of thalamus => internal capsule => somatosensory cortex

(optional but interesting) Difficulty maintaining focus does not necessarily mean ADHD. What are other psychological conditions that could explain inattentiveness?

Stress at home can often explain inattentiveness

*+++++* What spinal cord disease is being described? -It is the only one you can be born with (congenital), but it can be congenital or acquired. -Caused by the presence of a cystic cavity in the central canal of the spinal cord. -Affects anterior white commisures, interfering with the spinothalamic tract crossing over for the upper extremities nerves, resulting in... -Pain and temperature loss bilaterally and symmetrically across the chest, arms, and back -- *"cape-like" numbness*.

Syringomyelia

Microscope image: Dermatomyositosis >> called ___fascicular inflammation b/c all of the purple dots are where? -clinical presentation

That's why it's called *Extrafascicular* inflammation and *perifascicular* atrophy -- symptom of smaller cells on periphery as well clinical presentation: both pain AND rash in affected area.

Viruses like herpes and rabies travel along what part of the neuron? Anterograde vs Retrograde direction? What travels fastest along the axon?

The *Axon* Many things travel along the axon, like enzymes, etc. Anterograde is normal -- towards the synapse. Retrograde is backwards -- back towards the cell body. The viruses also spread from cell to cell along axons. Can travel either direction, so they spread really well. You can see the bigger things (vessicles, mitochondria) actually travel through the axon fastest.

Which part of the axon has the highest concentration of voltage-gated Na+ channels? How does this determine the directionality of an AP.

The *axon hillock* has the highest number of voltage-gated Na+ channels. Logic: => That's where the action potential starts. => If there were a lot of Na+ channels at the other end of the axon, APs might go in the wrong direction or reverse direction during transmission (antidromic conduction = towards the soma). => At the same time, this imbalance of number of channels is WHY action potentials are usually orthodromic in direction (from soma to terminal).

FLIP: *Guillain-Barre Syndrome* What is the *Endoneurium*? > Endoneurium = the intrafascicular connective tissue. > a layer of delicate connective tissue around the myelin sheath of each myelinated nerve fiber. > It is composed of several nerve fibers making up a primary fascicle

The *endoneurium* is characteristic of *what disease*? What is *endoneurium*?

What is stereognosis? What sensory/spinal pathway does it use?

The ability to feel things and determine texture. Uses the Dorsal Column-Medial Lemniscus Pathway

+++++ Microscope image: Polymyositosis >> called ___fascicular inflammation b/c all of the purple dots are where? -clinical presentation

The dark purple dots are located right around the muscle fibers That's why it's called *endomysial* inflammation -- within the muscle fascicle clinical presentation: *pain ONLY* in the affected area; NO RASH.

Cross section of the medulla -- where to find the *nucleus of F. cuneatus*, the *nucleus of F. gracillis*, and the *medial lemniscus* on a medulla cross-section. What synapse occurs in the medulla, which the cross section shows? This process is done by ___ ___ fibers.

The first synapse, where the primary neuron becomes the secondary neuron, is at the *medulla*. You can see the *medial lemniscus* here, which is the secondary neuron. An important thing to note here is that the signal crosses to the contralateral side via the internal arcuate fibers. Axons travel from FC and FG over to the ML via the *Internal Arcuate Fibers* (blue in IMAGE) -- these are internal in the spinal cord and make an ARC shape transferring signals from one nerve to another. From there, it goes up (out of page) into the pons and then the thalamus.

Phases of an Action Potential in terms of voltage/polarization and when and what channels open. Define depolarization and hyperpolarization.

The phases of the AP in an axon are a) the rising phase, b) overshoot (above 0 mV), c) peak, d) falling phase, and e) *hyper*polarization (less than resting potential) (Fig. 2). Increaseing membrane voltage is depolarization. Decreasing membrane voltage below zero is hyperpolarization.

What type of muscle receptor detects muscle "tension", either when contracting itself or passive stretching? Sends info out via *what type of fiber*?

The receptor is called a *Golgi Tendon Organ* It transmits info via Group *1b* fibers.

Embryology: Identify on a diagram: -Neural Crest -Neural Tube -Neural groove and Neural plate -Alar and Basal Plates -Marginal layer and Mantle Layer The spinal cord is directly a derivative of which of these?

The spinal cord is a derivative of the *neural tube*.

What are the two major arterial sources of circlulation of blood flow to the brain?

The vertebral arteries provide the caudal circulation, and the internal carotid arteries provide the more rostral circulation. These two circulations are joined via the posterior communicating arteries to form the Circle of Willis, a precautionary circle to avoid brain ischemia should one or the other of these two main circulations become compromised.

+++++ Describe the processes of *primary (rostral) neurulation* and *secondary (caudal) neurulation*. What does each form? The whole nervous system (NS) forms from what three basic parts (*CNN*) and what do these become, generally? Neurulation starts with the ___, which interacts with the ___.

The whole nervous system (NS) forms from three basic parts (*CNN*): Neural tube, Neural crest, and Caudal mass. Neural TUBE (CNS structures -- brain, brainstem, spinal cord segments C1-S1) Neural CREST (PNS structures) The notochord itself becomes and remains the *nucleus pulposus* in adult brains.

Differentiate between these in terms of what meninges (maters), etc. they include and whether they are in the head or spine/back: - Meningocele (head and spine versions) - Meningoencephalocele - Meningohydroencephalocele - Menigomyelocele - Spina Bifida Occulta

These are fluid-filled, balloon-like defects. *Meningoceles can be in the head or spine.* Brain/Head: - *Meningo*cele: these involve the meninges; they do not involve brain; located in the subarachnoid space. - Meningo*encephalo*cele: these involve the meninges, as well as some brain tissue, hence the "encephalo" part. not good. - Meningo*hydroencephalo*cele: these involve the meninges, as well as some ventricles, hence "hydro" for water/CSF. not good. Spine/Back: - Spina Bifida Occulta: not as severe as a meningomyelocele because it does *NOT involve the spinal cord* or any neural tissue. No protrusion visible on back; tuft of hair on back. - Meningocele: Involves meninges, just like head one but in spine. Fluid-filled sack in spine. Does not involve spinal cord/neural tissue. - Menigo*myelo*cele: involves meninges AND spinal cord; not good.

How do type 1 and type 2 muscle fibers stain? -- in a ___ pattern.

They stain in a *checkerboard* pattern. Which one is dark and which one is light varies. He also said it's important to note that the fibers are all touching each other. Fiber Types: -Note that the fiber type is decided by the neuron type innervating that particular myofiber. -type 1 = red (dark) meat, slow twitch; LEs -type 2 = white meat, fast twitch; UEs

*Guillain-Barre Syndrome* -Note: *LOOK FOR *ENDONEURIUM* ON A MICROSCOPE IMAGE*

This is a problem with *a peripheral nerve* -- signal does not make it all the way to the m. -A.k.a., acute inflammatory demyelinating polyneuropathy -An acute onset, immune-mediated demyelinating neuropathy -Many cases are preceded by an influenza-like viral illness -A distal and ascending paralysis and areflexia associated with loss of sensation a few weeks after a viral illness is the typical presentation. While most patients recover, a small percentage of patient can develop respiratory involvement and/or autonomic instability, and a larger group may end up with neurologic deficits. Plasmapheresis and IVIg treatment seems to be beneficial in clearing the antibodies

What is the role of *Lissauer's Tract* in the transmission of pain signals? What happens here? Where would you block pain relative to the vertebral level of an injury?

This is where the pain signal enters the spinal cord on the ipsilateral side. Then, from here, it shoots to the contralateral side to join the spinothalamic tract. The pain signal can also travel up Lissauer's tract for a few vertebrae before it crosses. Therefore, it is important to know if pain will still make it up the spinal cord if you cut it at a certain place. Some might be able to travel up Lissauer's tract. You would want to block pain higher up than the vertebral level at which it is entering. Lissauer's tract is like an exit, getting off of the pain fiber's highway and entering the spinothalamic tract in the substantia gelatinosa.

+++++ The *Intermediolateral Cell Column* and the *Nucleus Dorsalis* are located at and run the length of which vertebral level range? (He could very well ask about damage to one of those and where that would be)

Thoracic

Triad of sxs and DSM-5 criteria ADHD

Triad of sxs: (all related to eachother) 1. Inattention 2. Impulsivity 3. Hyperactivity DSM-5 Requirements: -Onset of Symptoms before age 12. -Symptoms present in 2+ settings. -Symptoms interfere with functioning. -Symptoms not better accounted for by other disorders. Sxs must be present in more than one setting. DOES NOT have to be in all settings. Requirement is 2 or more settings.

phasic vs tonic receptors

Two events happen that make us pay less attention to a constant stimulus: 1. Adaption- This occurs at the sensory receptor level. The receptor decreases its firing frequency. "Phasic receptors" - Receptors that completely adapt to the stimulus, i.e., stop firing after some time "Tonic receptors" - Receptors that continue to fire as long as the stimulus is present 2. Habituation- This occurs at the CNS level. The brain pays less attention to a constant stimulus.

+++++ Where are these dermatomes? -C2 -C4 -C6 -T4 -T10 -L3 -L5 -S2 Which spinal nerve sends pain signals to the thumb? (could be a direct question; often in question stems; like "everything below T2 is parlayzed," etc.)

Upper arm (lateral surface) C5 *Thumb* and lateral forearm C6 - mnem: thumbs up makes a "6" shape Middle finger C7 Little finger C8 Nipple T4 Umbilicus T10 Calf L4,5 Big toe L5 Heel S1 Back of thigh S2

Important Dermatomes to remember: -upper extremity -- hand -nipple line -umbilicus -inguinal region / ligament

Upper extremity: C6/C7/C8 in the hand Body: T4: Nipple Line T10: Umbilicus L1: Inguinal Ligament

Interneurons, when present, connect ___ to ___ neurons.

Upper to Lower motor neurons

Name the part of the thalamus that receives sensations of pain/temp from the Spinothalamic Tract and touch, 2 point diff., proprioception, texture, etc. from the Dorsal Column Middle Lemniscus Pathway and sends these signals to the somatosensory cortex.

VPL (Ventral PosteroLateral nucleus) of the thalamus.

+++++ -Where are the UMNs vs. LMNs located? -How to tell an Upper Motor Neuron lesion from a Lower Motor Neuron lesion? >> Key way to tell which motor neuron the lesion is in: know which one makes muscles spastic and which one makes muscles flaccid/atrophy.

You need to be able to tell these apart. Muscle weakness is a symptom of both of them. The *best way to tell them apart* is by: 1) *Muscle tone* -- increased or decreased, spastic or flaccid? 2) *Stretch Reflex tests* -- hyperactive or hypoactive/absent? GOOD Summaries: ==> Motor neurons are characterized as "upper" if they originate in the brain, and "lower" if they originate in the spinal cord. ==> Upper motor neuron disease causes stiffness, which is called "spasticity". This is because the inhibitory signals are not coming down the spinal cord. So basically, they can't move thier muscles but their muscles are twitching themselves. Lower motor neuron disease causes weakness, loss of muscle ("atrophy"). This is because no signals at all are going to the muscle. *UMN Syndrome*: The lesion is in the brain or spinal cord, proximal to the motor neuron that is affected. This leads to muscle *spasms* and increased muscle tone. They will have *hyper*active stretch reflexes. *LMN Syndrome*: The lesion is in the LMN itself (alpha motor neuron or gamma motor neuron) or a component distal to it; lesion must be outside of the spinal cord. This leads to inactive muscles and decreased muscle tone (atrophy, flaccid mm.). They will have *hypo*active or *absent* stretch reflexes for that muscle.

What is a learning disability? What are the clues that a person has a learning disability.

a difficulty with academic tasks that cannot be traced to an emotional problem, etc. discrepancy between the person's IQ and their achievements -- may have high IQ, but not performing well in school. Another clue is if they are not responsive to the best educational interventions. 8 categories / types of learning disabilities, based on what they have trouble with -- 3 with reading, 2 with math, as well as difficulties in writing, understanding what people are saying, and expressing what you are trying to say.

• What is an intellectual disability? • What are adaptive behaviors? What to know about adaptive behaviors and intellectual disabilities?

a disability characterized by significant limitations both in intellectual functioning and in adaptive behavior as expressed in conceptual, social, and practical adaptive skills. They have difficulty in adaptive behaviors adaptive behaviors- mechanisms we develop to meet personal independence and functioning, likely determined or influenced be previous life obstacles.

What are sympathomimetics? What common medicines are sympathomimetics?

adrenergic agonists; drugs that stimulate the nervous system (*decongestants*, cocaine, meth, caffeine). MNEM: cold medicines keep you up at night

*Botulinum toxin* prevents muscle contraction by preventing the release of ___ from pre-synaptic *SNARE complexes* in *NMJs*.

an acetylcholine antagonist; prevents release by terminal buttons

A peripheral nerve is composed of a spectrum of sizes of nerve fibers, both myelinated and unmyelinated. Electrical stimulation of nerve fibers in a peripheral nerve produces a(n) ___ action potential, the summation of many APs in individual axons.

compound AP

*Superficial Reflexes*: -elicited by what kind of stimulus -Plantar reflex -- the babinski sign is what? Is this reflex normal or abnormal?

elicited by gentle stimulation of skin 4 of them: 1. Abdominal 2. Cremasteric 3. Hoffman 4. Plantar >> Flexion - normal >> Extension (Babinski sign) - abnormal Basically, these are used to quickly confirm functioning in C1-L5, all the way up until the sacral region -- sacral controls genitals, anus, etc. and you test those with urogenital reflex tests.

Lissauer's tract and substancia gelatinosa on a spinal cord cross section

gelatinosa -- more clear on each side of the dorsal column

Brown-Sequard Syndrome

hemisection of the spinal cord Damage to half of spinal cord. Sxs: Loss of pain and temperature sensation on contralateral side of body. Loss of proprioception and discriminatory touch on ipsilateral side of body.

+++++++ MoA of *Benzodiazepines* (e.g. Valium) What about barbituates?

increases the *frequency* of *Cl- channel* opening at *GABAa* receptors. So that means they work at the dendrites and cell bodies / somas of neurons, as opposed to the axon terminals (e.g., SSRIs, botox) or synaptic clefts (degradative enzymes). This is a common MoA for drugs: interacting with intracellular signaling mechanisms (i.e., second messenger systems), affecting channels, the number of NT receptors on neuron surface, and/or altering gene expression. With benzos, they affect channels - chlorine channels. Barbiturates (e.g., Phenobarbital) increase the *duration* of GABAa Cl- channel opening

Neuroembryology- Learning Objectives

neuroembryology- the study of the embryologic origins and the development of different parts of the nervous system

-Axon Hillock appearance, microscope -What is *nissl substance* the same thing as? Where is it present and where is it absent? -What is the *initial segment* of the axon and where is it located? It is rich in ___ channels; thus it is the site of action for medications that block those.

relatively clear area because there is no *Nissl substance* (Nissl substance = RER); nissl substance stains purple; so the axon hillock does not stain much. *Initial segment*- the first part of the axon; has different appearance than the rest of the axon; comes right after the axon hillock. >> rich in *Na+ channels* -- this is where sodium channel blockers work.

NT *Acetylcholine* basics: -precursor -biosynthetic enzyme -nicotinic receptor: ionotropic or metabotropic? -muscarinic receptor: ionotropic or metabotropic? -degradative enzyme

see IMAGE

How does a stretch reflex work; the basics -- base it on the roles of: - *muscle spindle* - afferent *somatosensory neuron* -- what are the 3 kinds (numbered) - *interneuron* - the *two motor impulses* sent out of the spinal as a response, one stimulatory and one inhibitory. How many synapses are involved?

the signals often use an interneuron to bypass the brain/motor cortex -- makes the reponse much faster. SMART. Afferent neurons go from mm. to spinal cord -- 3 types -- Ia, Ib, and II In a stretch reflex, just know that *only one synapse is involved*. I suppose this assumes there is no interneuron. The withdrawal reflex, which is polysynaptic. at the end, 2 motor impulses are shot out simultaneously. One of them is excitatory and contracts a particular muscle. The other one is inhibitory, and relaxes any antagonistic muscles to prevent them from contracting. SMART.

What is the cause of repolarization and hyperpolarization?

too much potassium efflux The efflux of K+ causes the repolarization, but it overshoots the RMP, causing hyperpolarization

Meningiomas are tumors derived from which mater? Be able to identify dura, arachnoid, and pia mater on a diagram

tumors that grow from the arachnoid mater

*Molecular control of the Neural Tube* What do each of these genes/proteins influence the Neural Tube to become? • *Homeobox (Hox) genes* • *Sonic Hedgehog Protein (SHH)* • *Bone Morphogenetic Protein (BMP)* • *Nerve Growth Factor (NGF)* • What does the *rostral neural tube* vs. the *caudal neural tube* become in the postnatal CNS? (i.e., brain, brainstem, spinal cord come from what?) • Also, define the term *neuromere* (hint: structural aspect of the neural tube).

• Activation of the *Hox genes* tells the neural tube to *segment* into *neuromeres* (see bottom). This divides the neural tube into rostral and caudal sections (see below). • *Bone Morphogenetic Protein* results in the formation of *dorsal (sensory)* neurons. ^ i.e., "BMP induces a dorsal (sensory) pattern in neural tube development." • The *Sonic Hedgehog Protein* results in the formation of *ventral (motor)* neurons. ^ i.e., "SHH induces ventral (motor) patterns in neural tube development." • *Nerve Growth Factor* protects particular neurons by preventing apoptosis. If a neuron has NFG, it is quite protected. Neurons meant to die would not have this. ^ NGF is a *neurotrophin* -- "neuro" - brain + "trophin" - location determiner). Neurotrophins are a class of proteins that neurons migrate to and they are used to ensure the survival and safety of particular groups of neurons. • Rostral vs. Caudal Neural Tubes: - *Rostral neural tube* ==> brain and brainstem. - *Caudal neural tube* ==> the spinal cord, segments C1 - S1. >> the rest of the spinal cord is later completed by the caudal mass. • *Neuromeres* are *segments* of the neural tube that establish different aspects of the embryonic brain during development. As stated above, neuromere formation is induced by activation of the Hox genes. Neuromeres are divided up so that each carries different genetic traits, resulting in the development of different CNS structures.

What happens with *Myasthenia Gravis* at the NMJ in terms of antibodies?

• Autoantibodies against acetylcholine receptors on the post-synaptic membrane. • Immunological destruction of neuromuscular junction • Rapidly fading strength ('myasthenia') -- due to depletion of synaptic Ach • Association with thymic hyperplasia or thymoma; improvement after thymectomy • Association with other autoimmune diseases

Rostral vs. Caudal for -brain -brainstem/spinal cord

• Brain: rostral is towards forehead/nose (rostral nostril) and caudal is towards the back. • Brainstem/spinal cord below bend: rostral is up (towards the sky) and caudal is down (towards the floor).

What are Radiculopathies? -what element of of the peripheral NS is affected? -they are usually caused by what common back injury? -what area of the body will a radiculopathy affect? -radiation of pain is usually ...

• Injury to nerve root(s) -- commonly a herniated disc or other back injury. • *Pain & Weakness* specific to *affected nerve root level* -- Remember Dermatomes & Reflexes! • Pain often *radiates down affected limb* • Usually described by his pts as a pain that starts in the lower back and radiates down the affected limb.

-How and when is the neural tube formed? >> The neural ___ forms the neural ___ which forms the neural tube. >> By what gestational day should the production of a neural tube be completed? "L.O.: Distinguish between neural tube and neural crest."

• Picture it: there's a groove formed by two crests and the tops of those crests meet to form a tube in the middle. >> (Wiki): The neural groove deepens as the neural crests (folds) become elevated, and ultimately the crests meet and fuse at midline so that the *neural groove turns into a closed neural tube*. In humans, closure of the neural tube should occur by the fourth week of pregnancy (DAY 28). • The *Neural PLATE* folds to form the *Neural GROOVE*, which is then formed into the *Neural TUBE*. >> Remember: *Plate then Groove then Tube.* Neural Plate => Groove => Tube

• The *rostral* neural tube, which forms the brainstem and spinal grey matter, develops into what 3 primary vessicles? (a vesicle is like a lobe) • Those 3 vessicles then turn into what 5 secondary vessicles?

• Primary Vessicles: (1) *Prosen*cephalon = Forebrain (2) *Mesen*cephalon = Midbrain (3) *Rhomben*cephalon = Hindbrain • Secondary Vessicles: (1) Telencephalon -- P (2) Diencephalon -- P (3) Mesencephalon -- M (4) Metencephalon -- R (5) Myelencephalon -- R Mnem: Pros => Tel + Di Mes => Mes Rhomb => Met + Myel Mes stays Mes, Rhomb becomes the other two M's, and Pros becomes Tel and Di.

+++++ *Secondary Neurulation* (every card but this one and every part of the CNS except S2 and down, is primary neurulation) • Secondary neurulation is the formation of the __ __. • Occurs between gestational days ___ - ___. • This process involves the fusion of what two embryonic structures, which later *forms the spinal cord*.

• Secondary Neurulation is defined as the formation of the *caudal mass*. • Occurs between *gestational days 20-40*. • The *caudal mass fuses with the neural tube*, and thus *connects future S1 with future S2*. (primary neurulation = formation of neural tube and neural crest)

Course and Development of Autism: -Onset is usually around what age? -how does it affect the person over lifetime?

• Symptoms first observed at 12-24 months - Delayed language development, lack of social interest or unusual social interactions, odd play patterns, unusual communication patterns • Learning and compensation continue through life - Symptoms most marked during early childhood with gains in later childhood - Small number deteriorate behaviorally during adolescence, but most others improve • Few live independently as adults • Because they possess superior language and cognitive skills, many are able to find a niche that match their special interests and abilities • May still be socially naïve and vulnerable • Often are prone to anxiety and depression • Very little is known about elderly with ASD

++++++++++++++ What do each of these become in the human brain? (1) Telencephalon (2) Diencephalon (3) Mesencephalon (4) Metencephalon (5) Myelencephalon

• Telencephalon - *cerebral hemispheres & basal ganglia* ("end" brain) • Diencephalon - *thalamus, & hypothalamus* (be"tween" brain) -also posterior pituitary & retina. • Mesencephalon - *midbrain* ("mid" brain) • Metencephalon - *pons & cerebellum* ("after" brain) ^ MNEM: The pons "meets" (met) the cerebellum. • Myelencephalon - *medulla* (The "marrow" part of the brainstem)

+++++ • Why are infantile reflexes even checked? What information do they provide in general? >> Around what months of age do these primitive reflexes usually appear and disappear? • Doctors also check for asymmetry in these examinations. If infantile reflexes are asymmetrical, this likely indicates a lesion with what characteristics? • Name these important infantile primitive reflexes: 1) Tap/touch the smooth part of the forehead above and between the eyebrows, infant *blinks* once or twice. 2) Touch closed lips tear the midline, baby purses/pouts lips. It helps with feeding. (Name doesn't make that much sense, but it is an easy, normal word) 3) Similarly, if the cheeks or lips are touched, the baby will turn head towards source and make a sucking motion with the mouth.

• These reflexes appear and disappear at certain ages as the nervous system develops. These reflexes are checked to ensure that the brain is developing at the correct pace. >> These PRIMITIVE reflexes appear early (by 1 month old; to help baby survive) and disappear at ~6-7 months of age, and are then replaced my more complex reflexes. • Asymmetrical exam could indicate a lesion involving one side of the nervous system. • Reflexes: 1) Glabellar reflex >> Glabella is the smooth part of the forehead above and between the eyebrows. 2) Snout reflex 3) Rooting reflex

Milo, age 8, speaks in short sentences and often does not respond to when others are speaking to him. He appears socially odd even to those who do not know him well. He also becomes upset when his mother takes him on a different route to school and becomes distressed at school if he is not able to drink chocolate milk for lunch like he does every day. What severity level is being described? A. Mild B. Moderate C. Requiring Support D. Requiring Substantial Support E. Requiring Very Substantial Support

D. Requiring Substantial Support Only C-E are classifications of autism, and they are the only 3. In Levels 2 and 3 (Requiring Substantial Support and Requiring Very Substantial Support), there are marked deficits in verbal and nonverbal communication. If the child can speak FULL SENTENCES and communicate, it's level 1, even if conversational language skills are impaired (which they often are). language - does not respond socially odd becomes upset

Demyelination of a central nerve fiber, as in Multiple Sclerosis, may cause its conduction to: A. increase in velocity B. increase in size of AP C. decrease in size of AP D. fail E. show no change

D. fail

When are you supposed to get a DTaP and DTaP boosters for tetanus? DTaP vaccines work because they contain a(n) ___ to tetanus. Treatment of an actual tetanus infection involves first ___ and then giving the pt ___.

DTaP contains *tetanus immunoglobulin* An actual infection with tetanus can be treated with debridement (removal of foreign object) and ABx.

Subacute Combined Degeneration of the Spinal Cord (SCD) -related to ___ deficiency -Results in a deficiency of ___ of the spinal cord. -Caused by damage to what two spinal tracts, resulting in what sxs? -unique key sxs

Damage results in poor proprioception and vibratory sensation (dorsal column damage) and spastic paresis (damage to lateral corticospinal tract) Deficiency in myelination of *SCD* (same acronym): *S*pinocerebellar tracts, lateral *C*orticospinal tracts, and *D*orsal columns. Unique key sxs: *Beefy red tongue*, megaloblastic anemia (B12 def sxs) B12 Deficiency -- often Dietary in vegans; autoimmune DO with Ab to intrinsic factor; gastric bypass LE weakness with UMN signs - due to cord involvement Cognitive dysfunction Peripheral neuropathy -- weakness with LMN signs Megaloblastic anemia Copper Deficiency - Dietary, excess Zn intake, gastric bypass LE weakness with UMN signs Peripheral neuropathy Microcytic anemia

*++++++* Always on test *Tabes Dorsalis* (neurosyphilis) is a syphilitic infection that destroys *what section* of the spinal cord? Therefore what are the usual sxs?

Dorsal column trouble with proprioception, feeling texture, 2 point differentiation, etc.

What type of birth defect results from the failure of Neural fold *fusion* and/or neuropore *closure*?

Dorsal induction defects Involves primary and secondary neurulation defects.

Direction of the Corticospinal Tract along spinal cord / brainstem.

Down -- from brain to body. Efferent.

FLIP *Polymyositis* You can see *endomysial* inflammation and atrophy

Dx

Sample test question: Ionotropic receptors: a) Have a fast response to ligand binding b) Have relatively short duration change in ion flow c) Do not involve second messengers d) Directly effect ion channels e) All of the above

E) All of the above

A 75yo woman presents with a year of progressive difficulty standing & difficulty playing the piano. She has no sensory complaints. Exam: Severe weakness of proximal legs and distal arms. *Sensory exam was normal.* *Reflexes were normal.* Where in the peripheral NS would you localize this? a) Peripheral nerve b) Nerve root c) Motor neurons d) Neuromuscular Junction e) Muscle

E- Muscle Muscles are weak; she's old and she's been sitting down playing piano. A- nope; no sensory sxs B- No, no injury; affected area is not localized to a specific spinal cord level and pain does not really radiate down an extremity. C& D - nope; reflexes are normal; not enough -- doesn't explain everything.

The rising phase of the action potential is due to voltage-gated channels that allow ______ ions to flow across the cell membrane toward their equilibrium potential. A. K+ B. Ca++ C. Cl- D. Mg++ E. Na+

E. Na+

*+++++* "Important concept" and L.O. Define *Myotome* specifically but briefly; differentiate from a dermatome.

Every muscle that is innervated by a particular *spinal nerve*. > e.g., one spinal nerve innervates the biceps, brachioradialis, brachialis, etc. and all those mm. it innervates are collectively called the *myotome* for that spinal nerve.

There are 2 types of *motor* neurons: Extrafusal fibers are activated by __ motor neurons. Intrafusal fibers are activated by __ motor neurons. Difference between these fiber types?

Extrafusal -- alpha motor neuron Intrafusal -- gamma motor neuron Skeletal muscles contain special bundles of muscle fibers called muscle spindles that are involved in stretch reflexes. The muscle fibers *within* these muscle spindles are called *intra*fusal fibers. The muscle fibers *outside* these spindles, the regular skeletal muscle fibers, are called *extra*fusal fibers.

Where is the dorsal column? Consists of what two nerve tracts?

Fasc. Gracilis and Fasc. Cuneatus

Type Ia, IIa, IIb Muscle Fiber types -- Fast vs Slow Twitch -- Which is Which?

Fiber type is determined by innervation, not by the muscles. You cannot change your muscle fiber types.

How are the 3 amino acid NTs made from the same precursor?

Glutamine ===> Glutamate =====> GABA =====> degradation

The primary inhibitory NT in the spinal cord is ___. (i.e., the main inhibitor of spinal cord transmissions)

Glycine

*Muscle spindles *send out signals via what 2 groups of muscle fibers?

Group 1a fibers and Group II fibers. i.e., A alpha and A beta fibers.

Diagnose the *Neural Tube Defect* that occurs in newborns when these neuropores *fail to close* during embryonic development: 1. *Anterior* neuropore (rostral NP) (*mnem*) 2. *Posterior* neuropore (caudal NP) 3. *Both* neuropores (*mnem*)

IMAGE: Be able to identify these photographs. • *A*nt*E*rior neuropore doesn't close ==> *HEAD PROBLEMS*: 1) *An*encephaly or 2) *E*ncephalocele • Posterior neuropore fails to close: - *Spina Bifida* ("split spine") --- the three M's (e.g., Meningiocele) -- see IMAGE - spinal cord fails to close properly while in the womb. • If both Neuropores fail to close ==> *Better get a CT* -- baby is born with *Craniorachischisis Totalis*

Locations in cross section of lateral and anterior corticospinal tracts. Where in the brain or spinal cord does the decussation occur?

In the medulla

Previously healthy infant (<12 mo) with constipation; weakness in sucking, swallowing, or crying; muscle weakness

Infant *Botulism*

Which direction does the *Medial Lemniscus Pathway* of the *Dorsal Column* go along the spinal cord/brainstem?

Inferior to Superior (up) (afferent) Makes sense -- Dorsal is sensory the Dorsal Column-Medial Lemniscus Pathway is a sensory pathway of the central nervous system that conveys sensations of fine touch, vibration, two-point discrimination, and proprioception (position) from the skin and joints.

Muscle spindles consist of what kind of fibers? *Intra___ fibers.*

Intrafusal fibers

Microscope: Central Core Myopathy

Literally the name describes the image This is a congenital myopathy (from birth)

3 main peptide NTs 2 main gas NTs

MNEM: Peptides (opioids) put you to *BED*

Name the disease: 1) Demyelinative DO involving any part of CNS Young adults- affects ppl at the prime of their lives Required- Multiple lesions at different times in different places Tx: *Disease-modifying therapy*. 2) Demyelinative myelopathy involving long segments of cord Optic neuropathy Tx: *Immunosuppression* is tx.

Multiple Sclerosis (MS) Neuromyelitis Optica (NMO) (Devic's disease)

Which NT acts as a retrograde messenger, going from the postsynaptic cell to the presynaptic cell?

NO

The most reliable way to diagnose Tetanus is by its clinical presentation. What are the main signs of tetanus?

See IMAGE Background (on another card too): You get Tetanus when wounds are infected by spores from soil or feces. It releases a neurotoxin that binds to *motor* neurons and inhibits GABA, so you lose voluntary control of your muscles, but there is over-stimulation of motor neurons -- *spastic paralysis*.

You hit your thumb with a hammer. What fiber type carries the initial sharp "pricking" pain, and what fiber type carries the later dull/throbbing pain?

Sharp- A-gamma type fiber Dull/Throbbing- C type fiber

What spinal cord disease can be *diagnosed by genetic testing* and can be *treated with Antisense Oligonucleotide (ASO) therapy*?

Spinal Muscular Atrophy (SMA) Mnem/Explanation: It is a genetic disease that is caused by a mutation. If a specific mutation is known, ASO can be used, in which an antisense strain is made that can bind to and deactivate a particular mRNA strand.

Differentiate between the Mild, Moderate, Severe, and Profound Intellectual Disabilities. The DSM-4 differentiated severity based on IQ, but the DSM-5 now bases severity on ___.

The DSM-5 now bases ID classification based on the person's adaptive behaviors. It's a more practical approach -- how well does this person actually function in life -- that's what matters. To determine level of severity, consider: -how much help do they need with basic tasks? -how do they communicate? Full sentences, partial sentences, nonverbally (sounds), etc. -do they need to be monitored at all times? Can they learn how to live on their own (level of function). 85% are mild; 10% are moderate; 5% are severe and profound *Mild* Intellectual Disability if: • Often not noticed until the child starts having academic difficulties, usually in elementary school. • Difficulty learning academic skills for school-age children and adults; Poor executive functioning and short-term memory; Concrete approach to problems and solutions. • Immature social interactions; difficulty regulating emotions and behaviors; Limited understanding of risk; *risk of being manipulated*. • *Function appropriately*; Can handle basic skills and is capable of personal care, but might need help with more complex daily living tasks such as grocery shopping and planning/organizing; Employment options usually require only basic conceptual skills; May need support with health care and legal decisions. *Moderate* Intellectual Disability if: • Usually noticed in preschool. • Difficulty learning academic skills at all ages. As adults, academic skills are at the elementary school level. So for moderate and above, they reach a certain maximum intelligence, so there's no reason to even try to teach them geometry and stuff (...special ed). • Marked differences in social and communicative behavior; May not perceive or interpret social cues accurately; Social judgment is limited; Significant social and communicative support is needed in the work setting. • Functions appropriately with personal care though may need reminders; Participation in household tasks can be achieved with extensive teaching; Employment does not involve conceptual or communication skills. *Severe* Intellectual Disability if: • Should never be left by themselves; Unable to make or comprehend decisions for self or others. • Little conceptual skills; Little understanding of written language or concepts involving numbers. • Spoken language is single worlds or phrases; speech focused on present; Relationship are sources of pleasure and help. • Requires support in all aspects of daily living; Requires supervision at all times; Maladaptive behavior (self-injury) is present in a significant minority. *Profound* Intellectual Disability if: • Should never be left by themselves; Unable to make decisions for self or about others, May unintentionally harm self or others. • Can only understand the *tangible, physical world*; can recognize, match, and sort based on physical aspects. • No capacity for language; Limited understanding of symbolic communication; May understand simple directions; Can only express needs through *nonverbal* communication (sounds, etc.) • Requires support in all aspects of daily living; requires supervision at all times; Maladaptive behavior (self-injury) is present in a significant minority

Local anesthetics block ___-gated ___ channels.

Voltage-gated sodium channels signal can't continue up the cord

Importance of Alpha-Gamma Linkages/Coactivation

When α-motor neuron causes muscle contraction, muscle spindle becomes floppy and does not detect anything. Thus, when α-motor neuron causes muscle contraction, Golgi tendon organ is activated, but muscle spindle is not.

What is gray matter vs. white matter in the brain? Which would each of these be in? > Somas of neurons > Neuropils -- DEFINE by two components -- mnem: neuroPILEs ^ *What disease is caused by plaques in neuropils?* > Axons of neurons

White matter is myelinated, so axons. Non-myelinated stuff is in the gray matter. Gray matter is on the outside of the brain while white matter is on the inside. This is flipped in the spinal cord. *Neuropil*: neuroPILE - pile of brain cells -a PILE of grey matter neurons and glial cells. Composed of mostly unmyelinated axons, dendrites, and glial cell processes that forms a synaptically dense region containing a low number of cell bodies. -*Alzheimer's* is caused by beta-amyloid plaques in those neuropils.

Animation of an action potential in terms of changes in charge/polarity across the membrane of the axon as an AP travels along it. What causes this (in terms of Na+ and K+ channels opening and closing)

Wikipedia caption: As an action potential travels down an axon there is a change in polarity across the membrane of the axon. Stimulation of the neuron causes sodium- (Na+) and potassium- (K+) gated ion channels to open and close as the membrane reaches its threshold potential once the impulse reaches it. What happens? Na+ channels open at the beginning of the action potential, and Na+ moves into the axon, causing depolarization. Repolarization occurs when the K+ channels open and K+ moves out of the axon, creating a change in polarity between the outside of the cell and the inside. The impulse travels down the axon in one direction only, to the axon terminal where it stimulates the next neuron.

What would be the result of a spinal cord hemisection?

You would destroy a lot of stuff for that side -- but remember ipsilateral vs contralateral. Corticospinal tract, DC-ML pathway,

++++++ Botox (botulinum toxin) prevents the release of what NT from nerves?

acetylcholine

How does the diameter of an axon affect the speed of the nerve impulse?

bigger diameter = faster transmission also, the bigger the diameter of the nerve, the LESS stimulation it needs to fire. i.e., bigger diameter = lower excitation threshold.

The subarachnoid space contains __ __ and __ __ __

blood vessels and CSF

These Neuroblast Defects are due to messups in the organization, proliferation, or migration of neurons? -All of this type involve some amount of intellectual disability -Megalencephaly and Microcephaly are due to this type of defect; occur between __-__ months of pregnancy.

migration defects on another card

Pain is sensed by which somatosensory receptor?

nociceptors

*The Neuron*: Basics • What neuron structures are in these 3 neuron divisions? Karyon, Perikaryon, and Fibers

• see IMAGE

The *TDP-43 mutation* is associated with what disease?

*Amyotrophic Lateral Sclerosis (ALS)*

Renshaw cells -they are what type of neuron? -what is their function? -they use what NT to do this? -they control what kind of movements?

*Interneurons* that *INHIBIT* *alpha motor neurons* They use *glycine* as an inhibitory NT. act to focus fine motor activity.

If the arteries leading up to the brain burst, *where will the blood collect?* This is called a ___ Hematoma. It is because the blood vessels travel through this space. What are the other two types of hematomas (also based on meninges)?

*Subarachnoid space* Called a Subarachnoid Hematoma / Subarachnoid Hemorrhage 3 Types of Hematomas (brain bleeds): 1. Epidural Hematoma 2. Subdural Hematoma 3. Subarachnoid Hematoma

How do agonists and antagonists work at the receptor level? Where on the neuron do agonists and antagonists always act?

-*A*gonists *A*ctivate surface receptors because they mimic the NT that the receptor binds. -Antagonists block surface receptors. >> e.g., *A*lpha-*B*ungarotoxin is an *A*ntagonist that *b*locks binding of Ach to its nicotinic receptor in the neuromuscular junction. Agonists mimic the structure and effect of a particular NT; bind with the same receptors as the target drug Both of these work on the *soma/cell bodies* and *dendrites* of neurons, as opposed to the axon terminals (e.g., SSRIs, botox) or synaptic clefts (degradative enzymes).

There are two enlargements along the spinal cord. At what vertebral levels are these: -Cervical enlargement -Lumbosacral enlargement Why are these enlargements important? What comes out at each?

-C5-T1 -L3-S1 -Brachial plexus is at the cervical enlargement -Lumbosacral plexus is at the lumbosacral enlargement

FLIP *C* - Large Group Atrophy When the nerve that has reinnervated a large fascicle and resulted in fiber type grouping dies, then that entire fascicle becomes atrophic. This is called large group atrophy. It indicates a chronic ongoing neurogenic process, typically seen in neurodegenerative disorders such as spinal muscular atrophies (a type of motor neuron disease), where neurons in the spinal cord are constantly degenerating.

-Diagnosis? -- denervation of which of the following phases: a) early denervation b) chronic denervation c) late denervation Is this large or small group atrophy?

ADHD with comorbid anxiety: -What type of ADHD tends to be comorbid with anxiety? -How do anxiety symptoms affect ADHD symptoms? -Possible role of trauma; PTSD

-Inattentive type tends to get anxiety -Anxiety actually reduces ADHD symptoms; increases focus and alertness. -Need to check for trauma/PTSD as well -- sxs often resemble those of ADHD w/ anxiety.

What are Pacinian corpuscles? Explain how these produce *graded potentials* rather than action potentials and how they are *non-propagating*

-respond to deep pressure and vibration -graded - different intesities of signals can be generated by different intensities of stimuli --- as opposed to action potentials, which are all-or-nothing.

+++++ What are the four ways that *Repetitive/Restrictive behaviors* can manifest in ASD? (2 or more required for an ASD dx -- requiring >1 allows more specificity since sxs can overlap w/ other DOs)

1. Stereotyped/repetitive use of speech, motor movements, or use of objects -Echolalia- meaninglessly repeating part of what the other person just said. 2. Excessive adherence to routine, ritualized use of verbal or nonverbal behaviors, excessive resistance to change. -need for things to be done in a very particular way or they feel stressed, and they're fairly inflexible to changes in routine. -e.g., eats cheerios for breakfast every morning; severely stressed out if one morning they're out of cheerios. 3. Highly restricted/fixated interests -often have one particular interest and know everything about it. Everything is about that topic, even in conversations. -preoccupied with these fixations 4. Hyper- or Hyporeactivity to sensory input or unusual sensory interest -touch; tactile sensitivity; certain clothing might irritate them, etc. -loud sounds, sudden overwhelming stimuli -or they could appear oblivious to things like a person's touch, voice, etc.

A lesion in what type of motor neuron would cause these sxs: 1. Spasticity (certain muscles continuously contracted) 2. Fasciculations (muscle twitches) 3. Ataxia, Intention Tremor

1. UMNs -- Pyramidal neurons in cortex of Cerebrum 2. LMNs -- Alpha motor neurons exiting the Brainstem & Spinal Cord 3. Purkinje fibers/neurons in Cerebellum

+++++ In the developing brain, after the secondary vesicles (e.g., dien-, meten-, telencephalon) form, 3 fissures (kinks) form. Where are these located? What does each become?

2 VENTRAL: -Cephalic flexure (midbrain region) -Cervical flexure (between hindbrain & spinal cord) 1 DORSAL: -Pontine flexure (becomes fourth ventricle = rhomboid fossa)

Reading Disorder

A deficit in reading comprehension, written spelling, and word recognition.

What is /What is the purpose of a *Myotatic (stretch) reflex*? Biggest / most common example? How to think about and learn each myotatic (stretch) reflex / what to know about each > Good for organization because there is a lot of different info, so categorize it by these. Note: Myotatic reflexes are also called: > Muscle Stretch Reflexes > Deep Tendon Reflexes > Tendon Jerks

A myotatic reflex is an automatic, involuntary muscle contraction response to a sudden stretching of a muscle that serves to protect our muscles from being stretched out too far. These would usually happen if you did not intend to stretch a muscle. ^ EXAMPLE: *Knee-Jerk Reflex* - hammer shortens a tendon and stretches a muscle out ==> muscle spindle receptors sense that ==> reflex contracts muscle, which entends the leg. Rules & Things to Know for Each Reflex: -keep the *motor neuron* as the priority -- it is the key player in all of these reflexes -- What motor neuron is involved here? What is it doing in this reflex? <== usually the main motor neuron will send a quick message to a muscle as a response to a stimulus. -know what other players help in the reflex (i.e., the "components") -- where are they and how do they help? -know how those key players in the reflex interact with eachother to receive the signal and perform the reflex response. -And finally, overall, know what happens when a muscle is stretched. These reflexes involve 2 components: an afferent nerve (*somatosensory neuron* that goes from the receptor to the spine) and then an efferent nerve (*lower motor neuron*) that leaves the spinal cord on the same side to go back to whatever muscle and triggers whatever response.

Psychiatric "illness" vs "disorder" -- when does an illness become a disorder?

A psychiatric illness becomes a disorder once it causes impairment in functioning.

*++++++* Administration of a local anesthetic causes the shape of an action potential to change. The new shape is due to absence of membrane current of A. Na+ B. K+ C. Cl- D. Ca++ E. Mg++

A. Na+

At threshold of a nerve fiber, development of an action potential requires a change in permeability (conductance) first of which ions? A. Na+ B. K+ C. Cl- D. Ca++ E. Mg++

A. Na+

ADHD medications -Main treatments (2 classes) -SEs -Affects what NTs?

ADHD is the only psychiatric disorder in which medication is the first-line treatment. Increases levels of *Dopamine* and *NE* by blocking their reuptake. SEs: Appetite suppression, nausea, stomach-ache Mood changes: sadness, dampening, agitation Rebound Jitteriness Growth delay by age 21

Where, relative to the vertebral level of an injury, should a cordotomy (spinal cord cut to relieve pain) be performed?

At least 2-3 segments above where the pain signal is entering the spinal cord. Pain can travel *UP* (vertically) Lissauer's tract before crossing over -- so you need to be sure you cut it off above (after) the crossover, or pain can still travel up the other side.

What is a "fiber"?

Axons in the peripheral nervous system are called fibers because some of them conduct action potentials toward the cell body. Myelin also really helps with this. Signals weaken even more in unmyelinated axons.

Plexopathies, such as ALS, affect: a) Nerve Root b) Motor neuron c) Peripheral nerve d) NMJ e) Muscle What is a Plexopathy?

B- Motor Neuron -- affects BOTH upper and lower Plexopathy is a disorder affecting a network of nerves, blood vessels, or lymph vessels. The region of nerves it affects are at the brachial or lumbosacral plexus. Symptoms include pain, loss of motor control, and sensory deficits. Pain is often a first sign followed by extremity weakness and sensory loss. Main one to know is *Amyotrophic Lateral Sclerosis (ALS)*

At its resting state, membrane permeability to which ion is largest? A. Na+ B. K+ C. Cl- D. Ca++ E. Mg++

B. K+ The equilibrium potential is very close to the RMP for K+, thus K+ flows pretty freely across the membrane all the time.

Propagation of action potentials is necessary for an action potential to travel more than a few millimeters because A. voltage-gated Na+ channels inactivate in a few milliseconds B. the resistance of axoplasm to the flow of ions is very high C. voltage-gated K+ channels remain open too long D. the capacitance of axonal membrane decreases E. ions do not traverse the axonal membrane

B. the resistance of axoplasm to the flow of ions is very high The signals would die out from the resistance, so they are re-booted at each node.

Why is a lumbar puncture done in the lower back (L3/4 region)?

Because the spinal cord has become the cauda equina at that point (happens at L1/L2) -- you really want to be sure you don't puncture the spinal cord.

Broca's area is located: -in the __ __ gyrus -what lobe? -what side? Wernicke's area location

Broca's area: > Inferior frontal gyrus > left frontal lobe Wernicke's area: > Posterior superior temporal gyrus > Left temporal lobe *L*anguage is in the *L*eft hemisphere

23-year-old man drives home in a rainy night and runs into a ditch while texting a friend. On examination you find a dislocation of a vertebra that damaged the spinal cord. His motor control and sensation of the upper limbs appear normal. He has lost muscle control and joint position sense in the right leg. On the right side at the level of the umbilicus, he has a band of anesthesia. He also lost pain and temperature sensation on the left side 2 segments below the level of the umbilicus. How do you describe this lesion?

Brown-Sequard syndrome hemisection of the spinal cord at T10, R side

CT vs MRI of head, especially for strokes/TIAs

CT is much faster, great for revealing brain bleeds; fluids. MRI is quite slow; probably wouldn't order one in an emergency; but you would use an MRI if you want to see *tissues*, such as tissue damage from a stroke or presence of tumors (which are fleshy).

An axon can form a chemical synapse with what 3 things? Nomenclature: Axo___ synapse (3 of them)

Chemical synapses have NTs in them Axosomatic - axon to cell body Axoaxonic - axon to axon Axodendritic - axon to dendrite

Brachial plexus basics to know for this test C5-T1 spinal nerves What levels are these muscles at?: > Arms: -biceps -brachioradialis -triceps >Legs: -knee jerk reflex -ankle jerk reflex

Common Motor Reflexes: Arms: C5-C7 Biceps (C5/6) Brachioradialis (C6) Triceps (C7) Legs: Patellar (L3/L4) Ankle Jerk (S1)

ADHD with comorbid *disruptive behavior*: -The comorbidity rate is around ___% -What does a child with both ADHD and a disruptive behavior disorder look/act/feel like? -What are the common outcomes of this combination?

Comorbidity: *50*% When Conduct Disorder and ADHD coexist, often have more serious disturbance, more depression, more substance abuse, & more adult criminal activity. Combination is disastrous ==> antisocial behaviors and depression/depressive behaviors (e.g., substance abuse starting early). Outcome: More likely to participate in crominal activity as adults (AS behaviors)

Outline: Categories of Spinal Cord Disorders (for upcoming cards)

Congenital (described in future lecture) Hereditary / Degenerative Infectious Neoplastic Demyelinative & Autoimmune Nutritional Vascular Spondylosis / Trauma (all upcoming cards)

The very end of the spinal cord, before it becomes the cauda equina, is called the ___ ___. At what vertebral level does the spinal cord end?

Conus Medullaris L1-L2

Pathway of the *Ventral Spinocerebellar Tract* (*VST*): -does it cross sides? -How many neurons total? -enters the cerebellum at which peduncle? -type of info it carries and for what vertebral levels?

Crosses sides *twice* -- once right away, and again right at the end of the pathway. *Two neurons* Enters the cerebellum at the *Superior cerebellar peduncle* Touch and pressure T1 and below (everything except the cervical cert.)