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-Neuroscience Questions-
Questions 1-10 For questions 1-5, match the following clinical scenarios to the corresponding abnormality: 1. A 49 year old man has progressive weakness of various muscle groups, although his cognition is normal. He eventually dies of respiratory failure. 2. A 60 year old man has progressive forgetfullness and personality changes. 3. A 38 year old woman has depression, an intention tremor, and disturbed gait. 4. A 50 year old man has a slow resting tremor and loss of facial expression 5. A 10 year old boy has loss of coordination and muscle strength, as well as hyperreflexia
A. Low pigmentation in the lucus ceruleus B. Atrophy of the caudate nuclei C. Motorneuron degeneration in the anterior horns and cerebral motor cortex D. Demyelination of the corticospinal tracts, posterior columns, and spinocerebellar tracts E. Neuritic plaques with granulovacuolar degeneration
6. During a rugby game, a 25 year old male was tackled and became unconscious. Fellow players say he regained consciousness after a few minutes. He sat out the rest of the game but otherwise appeared normal. Later that evening he complained of a headache and soon had a seizure. At the emergency room he was given a CT. What did the CT most likely show? A. diffuse bleeding B. unilateral hematoma with distinct borders and midline shift C. unilateral hematoma with unclear borders and infratentorial herniation D. bleeding in the third ventricle
7. A 52-year-old male comes to the ER with a severe headache. He has ptosis of the right eyelid, and his right eye looks down and out. His right pupil will is dilated and does not accommodate. Aneurysm of which of the following vessels could cause this? A. Anterior communicating artery B. Posterior communicating artery C. Ophthalmic artery D. Posterior inferior cerebellar artery E. Anterior cerebral artery
8. A pregnant 25 year old woman is being evaluated for an increased AFP in her serum. Ultrasound confirms a malformation of the anterior end of the neural tube. Why is she likely to have polyhydramnios? A. renal agenesis B. increased urine production by fetus C. lack of midbrain reflexes D. fetal thalamic deregulation
9. Fasciculations are predominantly a sign of A. lower motor neuron lesion B. upper motor neuron lesion C. both A and B D. none of the above
10. The embryonic origin of the thalmic nuclei is from: A. telencephalon B. diencephalon C. mesencephalon D. metencephalon E. myelencephalon
Answers 1-10 1. Answer C This is ALS, where both upper and lower motor neurons are lost. 2. Answer E This is Alzheimer's. There would also be neurofibrillary tangles 3. Answer B This Huntington disease. There would also be atrophy of the frontal cortex 4. Answer A This is Parkinson's. 5. Answer D This could be either B12 deficiency or Friedrich's ataxia
6. Answer B This is the classic presentation of an epidural hematoma. There is a lucid phase followed by coma or seizure. The bleeding is often from the middle meningeal artery, which runs beneath the temporal bone and above the dura mater. The bleeding is limited by the suture lines of the skull (distinct borders), creating the appearance of a convex lens on CT. This would likely push the brain past the sagital midline. Here's a picture: http://www.med.mun.ca/anatomyts/radioanat/radiology/ ken/epidural02.JPG
7. Answer B Aneurysm of the posterior communicating artery can cause CN III palsy. A more common place to have an aneurysm is the anterior communicating artery, which is more likely to cause visual field defects.
8. Answer C The fetus has anencephay, which prevents formation of the brain, including the region responsible for the swallowing reflex. Without swallowing the amniotic fluid, polyhydramnios results.
9. Answer A Fasciculations are a sign of LMN lesions, as is weakess, atrophy, and diminished reflexes.
10. Answer B
Questions 11-15 11. Which of the following support cells in the nervous system is neural crest in origin? A. astrocyte B. oligodendocyte C. microglia D. Schwann cell E. ependymal cell
12. How many cranial nerves exit through the jugular foramen? A. 1 B. 2 C. 3 D. 4 E. none
13. Serotonin is predominantly synthesized in what region of the brain? A. locus ceruleus B. substantia nigra C. raphe nucleus D. basal nucleus of Meynert
14. Sensory information from CN V is relayed through what nucleus in the thalamus? A. VPM B. LGN C. MGN D. VA/VL
15. Loss of feeling in the right foot most likely came from infarction of A. right anterior cerebral artery B. left anterior cerebral artery C. right middle cerebral artery D. left middle cerebral artery E. right posterior cerebral artery F. left posterior cerebral artery
Answers 11-15 11. Answer D The Schwann cell is neural crest in origin
12. Answer C Cranial nerves IX, X, and XI exit through the jugular foramen.
13. Answer C Serotonin is from the raphe nucleus. The locus ceruleus makes NE, the substantia nigra makes dopamine, and the basal nucleus of Meynert makes acetylcholine.
14. Answer A The VPM (ventral posterial medial nucleus) relays information from V to cortex. Here's a good mnemonic: Girls put Very Pretty Makeup on their face. The lateral geniculate nucleus is involved in visual input, and the medial geniculate nucleus is for auditory input.
15. Answer B Sensory information for the lower extremity is in the area supplied by the anterior cerebral artery. If you're not sure why, find a homunculus.
Questions 16-20 16. The posterior communicating artery connects A. the vertebral artery to the middle cerebral artery B. the middle cerebral artery to the anterior cerebral artery C. posterior cerebral artery to the internal carotid artery D. vertebral artery to the middle cerebral artery E. right anterior cerebral artery to the left anterior cerebral artery
17. The vessel that passes through the foramen spinosum is most likely to cause which of the following if it is damaged? A. epidural hematoma B. subdural hematoma C. subarachnoid hemorrhage
18. Freidreich's ataxia is most similar in it's pathogenesis to A. myotonic dystrophy B. Creutzfelt-Jakob disease C. HNPCC D. cleft lip E. amyotrophic lateral sclerosis
19. A 37 year old man complains of "uncontolled movements when he reaches for things". His wife says he has been acting different for the past year. They both agree that he is getting worse and fear that 'he is dying the same way his father did'. What chromosome is involved in his condition? A. 4 B. 7 C. 11 D. 17 E. 18
20. To avoid a potentially fatal complication, tranylcypromine should not be prescribed with which of the following? A. amitriptyline B. phenelzine C. desipramine D. fluoxetine E. imipramine
Answers 16-20 16. Answer C The posterior communicating artery takes blood from the posterior cerebral artery. Since the internal carotid artery becomes the middle cerebral artery, the posterior communicating artery could also connect the posterior cerebral artery to the middle cerebral artery.
17. Answer A The middle meningeal artery passes through the foramen spinosum and, when ruptured, can cause an epidural hematoma (famous for having a lucid interval).
18. Answer A Both Freidreich's ataxia and myotonic dystrophy are from triplet repeat expansion. The other two noteworthy diseases are Huntington's chorea and Fragile X.
19. Answer A Huntington's chorea is caused by a CAG repeat expansion on chromosome 4.
20. Answer D Tranylcypromine is a monamine oxidase inhibitor (MAOI). Usually, the question asked about these is what foods should be avoided when taking a MOAI. Foods high in tyramine such as beer, cheese, and sausage. Just remember that nobody in Wisconsin takes an MAOI and lives. Of equal importance, however, is to know that MAOIs can't be prescribed with SSRI's such as fluoxitine, sertraline, and citalopram. Serotonin syndrome could result in death from cardiovascular collapse.
Questions 21-25 The following will apply for questions 21 and 22 A patient has a constricted right pupil, compared to the left. To diagnose Horner's syndrome, the physician first turns on a bright light. Both pupils constrict. Upon turning the light off, the right eye is slow to dilate. Next the physician administers two drugs to the eyes. The drugs are not given at the same time (ie they don't interact).
21. Which result indicates preganglionic Horner's syndrome?
22.Which result indicates postganglionic Horner's syndrome?
23. A 68 year old man wakes up in the morning to find that he has trouble walking, his voice is hoarse, and he has trouble eating. He comes to the ER and is found to have diminished gag reflex and his palate sags to the left. In addition, he has no pain sensation on his left face. He continues to complain of being dizzy. What vessel was likely obstructed? A. middle cerebral a. B. basilar a. C. vertebral a. D. AICA E. PICA
Answers 21-25 21. Answer B Preganglionic lesions mean that the postganglionic fibers going to the eye are still intact. Therefore, the release of NE can be induced from those nerves by an amphetamine, such as hydroxyamphetamine. Since cocaine acts by preventing the reuptake of NE, it would have no effect on a nerve that isn't firing.
22. Answer A If the problem is postganglionic, then there is no nerve to affect with hydroxyamphetamine. Therefore, there will be no change in the right pupil no matter what is done.
23. Answer E This constellation of symptoms is from occlusion of the left posterior inferior cerebellar artery, which is a branch of the left vertebral artery.
Fact Recall: Worst headache of your life? subarachnoid hemorrhage Ependymal cells make CSF Microglia and macrophages are mesodermally derived Astrocytes, ependymal cells, oligodendrocytes, and Schwann cells are ectodermally derived Most common site for berry aneurysm? anterior communicating artery Horner's syndrome can occur with lesions above T1 Which cranial nerve is affected by aspirin? VIII - salicylism results in tinnitus CNs involved in parasympathetics? III, VII, IX, X Nucleus ambiguus gives rise to what? IX and X
Notes: LECTURE 1 What are four CNS supporting cells? Astrocytes, Microglial (phagocytic cells), Ependymal Cells, Oligodendrocytes What is tic douloureux? Erosion of usually the trigeminal nerve, causing the nerves to become excitable, very painful What are the PNS supporting cells? Schwann and Satellite cells What is the supratentorial sections of the brain? Above the cerebellum, brainstem What is the posterior fossa? Infratentorial--- brainstem and cerebellum What are the gray matter in CNS? Nuclei, basal ganglia, thalamus, cranial nerve nuclei, ganglia What are the white matter in the CNS? Tract, fascicle, lemniscus, bundle, commissure, nerves If you have an injury to the supratentorial part of the brain, what would it look like? Loss of sensation and/or weakness on the same side of the face/body, contralateral to injury If you have an injury to the posterior fossa? Cerebellar and cranial nerve deficit; loss of sensation/weakness on opposite sides for face/body Ipsilateral to face deficit, cranial deficit and cerebellar deficit What is the role of the anatomical level of the cerebral hemispheres? The brain—thinking, intelligence, memory, emotion, voluntary action, awareness of sensation, vision, LANGUAGE What is the role of the brainstem? The “head” eye movements, facial movements/sensation, hearing and balance (motor CN) What is the role of the spinal cord? The” body”—neck, arm, hand, chest, abs, leg, foot, sphincter LECTURE 3-4 NEUROEMBRYO Where does the initial neural tube stop? S1 What is secondary neurulation? The caudal neural tube originating from the caudal eminence What are the parts of the forebrain? Tele and Diencephalon What are the parts of the midbrain? Mesencephalon ( cerebral aqueduct, tectum, red nucleus, substantia nigra and crus cerebelli) What are the parts of the hindbrain? Metencephalon (pons and cerebellum) and myelencephalon (medulla) What comes from the diencephalon? Optic Cup, Thalamus, Hypothalamus, Mammillary bodies, part of the 3rd ventricle What comes from the telencephalon? Hemispheres, cortex, hippocampus, basal ganglia, lateral and third ventricles Where is the pontine flexure? Between the metencephalon and the myelencephalon Where is the rostral flexure? Between the diencephalon and the mesen How about the cervical flexure? Myelenceph and spinal cord Where is the foramen of monro? Between the lateral ventricles and the 3rd ventricles What is the alar plate? The sensory neurons How about the basilar plate? Motor and interneurons What separates the two? Sulcus Limitans Where does the dural sac terminate in an adult? S1 Where does the spinal cord terminate in an adult? Near the L3 Where does the filum terminal terminate? L2-C1 What is the olivary nucleus? Forms after the alar neurons migrate down away from the roof of the 4th ventricle in the hindbrain What is the order of the hindbrain columns? Sensory: vestibular, skin, taste, gut innervation (Sulci Limitans) Motor: nonstriated, branchial striated (facial expression) and somatic striated (traditional skeletal muscle motor neurons) What happens to the roof of the 4th ventricle? It interacts with the vasculature generating capillaries, giving rise to the choroid plexus, which is responsible for secreting plasma into the lumen to form CSF How does the CSF get to the subarachnoid space from the choroid plexi? Foramen Luschka and foramen Magendie Why is the rhombencephalic isthmus important right now? It generates Transcription Facotrs and secreted factors like FGFs WNts and BMPS (like the cells of the roof and floor plate) What are the inferior colliculi associated with? Superior colliculi? Inferior: auditory; Superior motor Which Cranial Nerves have neural crest origins? III, V, VII, VIII, IX, X (3, 5, 7,8,9, 10) The cranial nerve parasympathetic ganglia arise soley from? Neural Crest What is the origin of cranial sensory ganglia? Some from neural crest, and some from ectodermal placodes The closer you are to the brain The more likely your cranial nerve sensory ganglia arose from neural crest What does the rhombencephalon give rise to? The cerebellum and the pons along with the medulla What does the myelencephalon differentiate into? The medulla oblongata What is the function of the medulla? The relay center between the spinal cord and the brain-à it houses most of the CN nuclei, and also controls nerve networks that regulate respiration, heartbeat, reflex movements etc What is the function of the pons? Relay signals between the spinal cord and the cerebral and cerebellar cortices What is the function of the cerebellum? Center for balance and postural control What is the function of the lateral geniculate? Sight (this is within the thalamus) What is the function of the medial geniculate? Hearing (this is also within the thalamus) Where is the pineal gland found? Behind the epithalamus What is the infundibulum? It develops in the floor of the 3rd ventricle and grows ventrally; it forms the posterior pituitary What is Rathke’s pouch? It is a diverticulum that grows dorsally to meet the infundibulum What is the corpus striatum? Lateral to the thalamus (medial to the internal capsule), in the lateral ventricles, that give rise to 2 of the 3 basal nuclei of the cerebral hemispheres (important in parkinson’s) What are the fibers of the internal capsule doing? Passes through the corpus striatum and carries fibers from the thalamus to the cerebral cortex, as well as from the cerebral cortex to lower regions of the brain and spinal cord What does the inferior colliculi do? Superior? Inferior: auditory; superior: motor ocular What forms a rough border between the diencephalon and the telencephalon? Foramen of Monro Where does the thalamus and the hypothalamus come from? The Diencephalon LECTURE 5: LAB LECTURE 6 What is an example of a Neural Tube Form defect, affecting the anterior neuropore? Myelomeningocele (cystic fibrosis), with associated disorder, Arnold Chiari Malformation What is Arnold Chiari Malformation? Stenosis of aqueductà causing hydrocephalus.. the cerebellum protrudes into the cervical canal, blocking CSF drainage--- resulting in hydrocephalus How is it fixed? VP shunt, or carved out skull What happens when anterior neuropore doesn’t close? Anencephaly: no supratentorial brain, some brainstem; or occipital encephalocele What are some disorders associated with prosencephalic development? Holoproencephaly What is holoproencephaly? Failure of the horizontal, sagittal or transverse cleavages of the proencephalon What are the stages of neuroembryological development? 1. Formation of the neural tube (Dorsal Induction) 2. Prosencephalization (ventral Induction) 3. Proliferation 4. Migration 5. Organization 6. Myelination When does the first stage occur? 3-4 weeks Second stage? (ventral induction?) 4-6 weeks What is a disorder associated with ventral induction? Holoproencephaly When does the third stage occur? 8-12 weeks What is a disorder associated with the 3rd stage? (proliferation) Neurofibromatosis What is a disorder associated with neuronal migration? Lissencephaly (type I Miller Dieker) or Type II (walker Warburg) What is the difference between males and females in lissencephaly? Well in type II, the X-linked one, females have the potential to have some neuronal migration, and end up with subcortical band heterotrophy What is a disorder associated with neuronal organization? Fragile X syndromeà disorders of neuronal synapse formation, (Praeder Willi, Angelman, DMD, Down’s What is Fragile X syndrome? autism associated, big ears, epilepsy, FMR1 associated protein expressed on ribosome (Sherman’s para.) What disorder did we talk about with myelination? Pelizaeus Merzbacher Disease What is this? Defect in proteolipid protein, little white matter formed, myelin missing What is Neurofibromatosis? A disorder of proliferation—where astrocyte tumors form on nerves, skin manifestations, café au lait spot LECTURE 7-8: Neuroradiology Where does the ACA supply blood to the brain? Near the midline of both hemispheres How about the MCA? A stroke to this area affect speech, motion, feelings of legs and face, and eyes deviate to the side of the lesion Where does the PCA supply? The occipital lobe; loss of blood here affects memory and vision What are the three things you should initially worry about with chest pain? Heart Problem, Lung Problem or Reflux Where are the choroid plexi relative to the foramen of monro? All posterior! Where does the PICA come off? Vertebrals Where does the AICA come off? Basilar How about the Superior Cerebellar? Basilar What are Hounsfield units? Normalized units of density for CT scans—bone: 1000, air: -1000; water: 0 fat: -50à-100 What are some hypodense or low density lesions? Usually high water content, or with fat or air: examples are cysts, edema, abscess, old blood, some tumors, lipomas etc What are some high density lesions? Usually contains blood, high protein, calcification (hemorrhage, calcified tumor, aneurysm) What are examples of intracranial hemorrhages? Epidural, subdural, subarachnoid, intraparenchymal What does an epidural hemorrhage look like? Won’t cross the coronal suture, but it CAN pass the midline, the arterial bleeding is bright and localizedàmore fatal than subdural What does a subdural hemorrhage look like? NO midline cross, but it CAN cross the coronal suture What does a subarachnoid hemorrhage look like? Most common form of hemorrhage, typically caused by aneurysms; blood is filling in the basilar cistern which causes a weak looking “5 point star” What does a Intraparenchymal hemorrhage look like? Focal bleeding into brain, typically due to hypertension or amyloids What does hypoxia look like? Patient loses the white/gray differentiation What are the types of edema? Cytotoxic (ischemia), vasogenic (disruption of BBB due to tumor or abscess), periventricular (acute hydrocephalus) What are the four major locations of aneurysms? Basilar Tip, Middle Cerebral Artery, Anterior Communicating Artery, Posterior Communicating/Bifurcation of Internal Car. What are the three aneurysm types? Berry, Saccular with a broad base, and fusiform
LECTURE 10 What is the MMSE? Mini mental status exam: orientation to time/place, recall 3 objects in 3 minutes, no ifs ands or buts, complex command, don’t throw rocks if you live in a glass house How do you test the optic nerve? Visual Field test, pupil size, reaction to light, accommodation, visual acuity, fundus exam How do you test the extraocular movements? Saccadic: jerky mvmts, pursuit: ability to smoothly follow one finger, convergence, nystagmus, diplopia, ptosis How do you check for CN V? Palpate masseter and temporalis, tongue depressor in teeth, pull (shouldn’t be able to yank out easily) Check for sensory, on 6 areas of the face How do you check for CN VII? Check for function and symmetry of facial expressions; try to pry open closed eyes CNVII? Soft finger rubbing CN IX and X? Tongue depressor, check for gag reflex CN XI? SCM, apply pressure to side of face, and ask patient to turn head CNXII? Tongue function and symmetry What is the scale for the muscle exam? 0-5; 0 is no mvmt and 5 is normal What is the Babinski sign? Refex test, curl toes under when making J on the bottom of foot What is double stimulation? Caliper, being able to distinguish two separate points What is stereognosia? Close eyes and ID objects with hands What is graphesthesia? Close eyes, and identify numbers or letters traced on their palm What is the muscle motor examination identifying, in particular? Tone, bulk, power and coordination What tests did he say are particularly useful muscle motor exams? MOTOR drift and Arm fix LECTURE 11&13 NEUROPHYSIOLOGY What is the normal membrane potential for neurons? -60à -70 mV What does excitability mean in a muscle? Action Potential and Contraction What is the normal membrane potential for muscle and glial cells? -80à-90mV Tell me about the membrane of a neuron? They are semi permeable to selective ions (K) What is the equation for flux? F= -P delta C where P= permeability of the membrane and C= the change in concentration What is equilibrium? When the NET movement of diffusing particles is zero What determines the rate of reaching equilibrium? The permeability of the membrane to the particles What is the relationship between the equilibrium potential and the concentration of a molecule outside the cell? Direct How about inside? Inverse Does the permeability affect the equilibrium potential? Only in how long it takes to attain ità not whether it can occur At room temperature, what does RT/F equal? 58 mV What is the ratio of [k] from inside the cell to outside? 50x more concentrated inside the cell Where is the Ca++ permeability the most important? In the soma, and the axon terminal What is the relationship between the permeabilities of K, Cl and Na in the axon? K>>Na=Cl When the cell is hyperpolarizing, is it becoming more positive or negative? Negative; depolarizing is more positive What ion has the largest permeability at rest, and thus has the largest impact on the resting membrane potential? K What is the Driving Force? The difference between the Nernst equilibrium potential for that ion and the resting potential What factors affect the Nernst equation? R=gas constant; T=temperature; z=charge on ion; F= faraday’s constant; [X] both inside and outside For potassium, what is the driving force? -90 minus -70, so -20mV (in the OUTward direction) For sodium, what is the driving force? +60 minus -70, so +130mV (Inward!) So, where does Na and K move? Sodium wants to move IN to the cell; Potassium wants to move OUT What is the Goldmann’s equation used for? To predict the resting membrane potential What does resistance tell you? How much current flows for a given voltage How do you calculate Capacitance? C=q/V; it tells you how much charge is needed to change a membrane potential by a given amount What qualities of a membrane are responsible for determining how fast a membrane can respond to a current? Resistance and Capacitance! What is specific resistance? Resistance/unit area : this is highly variable within and between cells What is specific capacitance? Capacitance/unit area: this is pretty standard from cell to cell à the larger the cell, the more the capacitance What is tau, the time constant? How fast the membrane can respond to current injection; time required to change the membrane potential to within 1/e (63% of its final value) àvalue independent of current, intrinsic to membrane What is length constant? Distance along the axon or dendrite over which potential decays to 1/e of its value at the point of injection (about 63%); increases with increasing diameter What is the relative concentration of the major monovalent ions inside and outside of neurons? Na+: +63 Ca++: 130mV K+: -89mV Cl-: -86mV What is the driving force for potassium? -20mV (Potassium wants to leave the cell) What is the driving force for Sodium? +130mV (sodium wants to get into the cell) What is an intrinsic property of the membrane? The time constant What influences the length constant? The diameter of the axon, and resistance (if the INTERNAL resistance increases, the length constant will decrease; if the MEMBRANE resistance increases, the length constant will increase) At normal membrane potentials, are Na channels open or closed? Closed What about at a membrane potential of 0mv? Most of them are open now When does inactivation of Na channels occur? After it is opened, and before it is closed Tell me about potassium channels? No inactivation period.. just open or close. When potassium channels are open, K+ moves OUT What are the phases of the AP? 1. Depolarization 2. Overshoot and turnaround 3. Repolarization phase 4. Hyperpolarization after potential Tell me about the depolarization phase Sodium ions start coming in, making the cell potential more positive… which activates more sodium gates to open (runaway cycle) note: not many ions actually enter the cell, but the membrane gets charged What about the overshoot phase? As the membrane is depolarizing, the Na+ channels are inactivating, while the potassium channels are slow to become activated, but now they are activated and K+ runs out… pushing the membrane potential back down again; gets to +60mV What about the repolarizing phase? The K+ channels are activating and the Na+ are inactivating What is required for the AP to initiate? Slight depolarization What about a cardiac muscle action potential? Same as the neuronal, but a longer duration How about the smooth muscle cells? Many more currents are involved What is the pacemaker effect? Just set the threshold below the normal resting potential and you will get continuous regenerative APs What is the importance of hyperpolarization? Prevents another AP from occurring simulateously and allows for the AP to be propagating in one direction What will you find at the axon hillock? Volgate gated Na+ channels What is the absolute refractory period? When you can put in as much current as you like and you still won’t get another AP. What is the relative refractory period? When another AP gets progressively easier to initiate. It might take 20ms or so before it goes back to the normal threshold Tell me about the Na+ K+ ATPase. Takes 3 Na+ OUT for every 2 K+ that it brings in, and it’s stimulated by high internal Na+ What is the neuronal consequence of diseases resulting in Hyperkalemia? Makes the membrane potential become more positive and shuts down activity What is the fastest type of myelinated nerve fiber? A alpha with an axon of 15 micrometers and a conduction velocity of 100m/s What is the slowest myelinated fiber? B with a fiber of 3 micrometers and a CV of 7 m/s (sympathetic preganglionic) What is Fiber C? Unmyelinated, real slow with a Diameter of 1 and CV of .5-2 m/s this carries pain Receptor potentials are proportional to the size of the stimulus Therefore, the stimulus may or may not initiate an AP What does the sodium channel look like? It has one large alpha subunit, and two smaller beta subunits that modulate alphaà HIGHLY conserved; there are four linked repeating segments each with six transmembrane-spanning regions: together they form the aqueous pore What is the voltage sensor of the Na+ channel? S4 What are the different types of Calcium channels? L, N, T, P/Q where T= low threshold, inactivating and found in neurons L= non-inactivating, HIGH threshold, found in neurons, endocrine cells and heart: dihydropyridine drug N= intermediate threshold, inactivating and often at synapse P/Q= intermediate threshold and inactivating What about the structure of Ca++ channels? 5 component heteromultimer with alpha 1 and 2, beta, gamma and delta subunits---similar to Na+ channels, where each alpha subunits has 4 repeats of 6 transmembrane regions What dictates the Ca+ channel type? The alpha1 subunit Tell me about the Potassium channels. There are at least 15 types, and alternative splicing gives even more variety—there is a · delayed rectifier potassium channel (major axonal and somatic voltage dependent, resemble Na+ channel) · anomalous rectifier potassium channel (becomes MORE permeable when hyperpolarized, stabilize mem pot) · calcium dependent potassium channel (activated by high intracellular Ca+ levels, very little voltage depend) Tell me about the Chloride channel classes. Three classes: ClC, CaCC and CTFR What is the CIC channel? There are 0-9, some activated by depolarization, some not 1 in brain; 6 in muscle What is the CaCC channel? Found in secretory epitheliua How about CTFR? cAMP regulated, Cystic Fibrosis Transmembrane Regulator in secretory cells What is DEG/ENaC? It is not voltage sensitive, and is blocked by amiloride, found in airway, and kidneys What is the structure of DEG/ENac? 3 subunits, alpha contains the pore, each subunt has 2 transmembrane segments and a P loop Where are TRP channels found? Sensory Nerve Endings (sensitive to heat, cold and mechanosensory) Why are they cool? They are equipermeable to Na, K, and some Ca permeability as well What channels does amiloride block? DEG/NaC and TRP channels What channelopathy has a defect in KCNQ1? Jervell Lang-Nielsen (long QT syndrome) What channelopathy has a defect in SCN1A or SCN2A (sodium channel)? Epilepsy—allows for increased excitability because of the small persistant inward Na+ current LECTURE 14: BLOOD BRAIN BARRIER What determines membrane permeability of drugs? Lipophilicity and ionization What does lipophilicity of a drug do to it’s ability to permeate membranes? INCREASES What if a drug is ionized? Can’t pass so well What if a drug has aliphatic or aromatic structures? It is prob lipophilic, and can penetrate membranes How about polar groups? Not gonna happen Why are amino acids, glucose and L-dopa able to penetrate the BBB, yet they are polar? They are substrates from some transport mechanism; without the transporter, glucose couldn’t pass into the CNS What is responsible for maintaining the BBB? Tight junctions, capillaries at the BBB lack fenestra; thus they must diffuse across transcellularly, meaning they must cross the cell membrane (necessarily being lowly ionized and highly lipophilic) ALSO, there is P-glycoprotein in the endothelial cells of the brain capillaries, which pumps drugs out of endothelial cells What “breaks the BBB?” Ischemia and inflammation What is the purpose of the BBB? Protect from xenobiotics, hormones and NT of the rest of the body, maintains a constant environment for brain What are substances that may not enter the brain? Peptides and proteins, toxins, Ab, Neurotransmitters What helps to compromise the BBB? Astroglia, they send processes which cover blood vessels What areas are NOT protected by the BBB? Area postrema, subfornical organ, pineal body, median eminence, neurohypophysis (posterior pituitary) What is the P-glycoprotein? Membrane transporter of the ATP binding cassette family (ABC family)-à gene for P-glycoprotein is ABCB1 or MDR1 What was the P-glycoprotein originally identified as? The multidrug resistance phenotype in cancer cells How does P-glycoprotein work? Keeps cytoplasmic concentrations low, it kind of swats back those that can get by passive diffusion—EFFLUX pump Why do some drugs fall off the regression for polar molecules and their brain uptake? Some are substrates for P-glyocoprotein, so even though they are soluble, they are swatted back What is interesting about ABCB1 or MDR1 polymorphisms? They can alter a person’s reaction to certain drugs, in particular the antidepressant, where the decreased p-glycoprotein ability allowed for more effective anti-depressants What causes disruption to the BBB? Trauma, inflammation, ischemia, hemorrhage, tumor, demyelinating diseases etc LECTURE 15 What is the difference between type1 and 2 synapses in the CNS? Type 1: synapses on the dendrite, round vesicles Type 2: synapses on the soma, flattened vesicles What happens at a synapse? Activation evokes PSP, AP invades the presynaptic terminal, vesicles fuse with the membrane at the cleft, release their contents into the cleft. Vesicles contain NT (usually each neuron releases only 1 kind of NT at its synapse) post synaptic side has the receptor (that dictates the effect on the neuron) Reuptake of left over NT, (or hydrolysis of it) What are the different types of PSPs? Excitatory and Inhibitory; excitatory depolarizes (drive toward threshold), where inhibitory is a hyperpolarizing (drive away from the threshold) When is an AP initiated? If the EPSP reaches threshold, begins in the axon hillock with a high density of Na channels What is the role of Ca++ in synaptic transmission? Ca++ enters at the terminal and allows the vesicles to fuse with the presynaptic membrane so that NT can be released, cross the cleft and excited the postsynaptic channels. What are the criteria for a NT? 1. There must be specific enzyme of synthesis of NT in presynaptic cell 2. Release of NT is ALWAYS Ca-dependent 3. There must be a postsynaptic receptor for NT 4. There must be an uptake mechanism or other way of terminating the NT action Why not use gap junctions? Transmission by gap junctions is inherently limiting because the voltage is shared What can you do to block the effects of Ca+? Extracellular Mg+ can go through the Ca+ channel and compete for Ca+ binding site---Mg is used as a treatment for epilepsy What can you say about EPSPs? It is the summation of many discrete packets (of NT), or quanta--- synaptic transmission is a quantal process What is the reversal potential? Where the K going out exactly matches the Na coming in (around 0 mV for Na & K) What is a example of an inhibitory NT? GABA: it’s receptor is a pure Cl channel Tell me about how GABA can be a IPSP. Cl has a small driving force at membrane potential, but the tendency is to move out of the cell; if you are moving in the depolarizing direction, the electrical gradient becomes smaller, so there is a higher tendency for Cl to come IN! Since there are more negative ions coming in, you get a larger IPSP! What is facilitation? During a train of EPSPs, they get bigger (more quanta are released) If you come back, get original size What is depression? Given a train of stimuli to the incoming axon.. get progressively smaller EPSP each time. If you wait a second or two and come back, you get same initial size of EPSP--- so not permanently modified What is similar between facilitation and depression? Both are Ca-dependent and pre-synaptic mechanisms, and neither of them persist beyond a few seconds (at NMJ & others) What is Post-Tetantic Potentiation? Longer term effect. Tetanus causes rapid stimulation and more powerful contraction; stimulates 5 per second, for several seconds--- high frequency of presynaptic stimulation---minutes to an hour later, eventually goes back to normal. (moderate) What is LTP? Long term potentiation? Major Change in the efficacy of the synapse. Much more rapid burst of stimuli (50 per second for several seconds). It is found in the hippocampus and cortex… suggests role in creating memories What is LTD? Long term depression? Found in the cerebellum and hippocampus; evoked by prolonged low frequency stimulation (1 per second for 15 minutes)—possible memory erasure mechanism (decreased synaptic efficacy) What are the second messenger systems? Usually G protein mediated, where the 2 messenger systems are slower than fast synaptic transmission, the ligands may be NT or short peptides—neuromodulation rather than neurotransmission What types of G proteins are found in the brain? G0 What does the alpha subunit normally activate in the G protein? Ion channels How about the beta/gamma subunit? IP3/DAG pathway What is the negative ionotropic effect? G protein directly opens the K channel, hyperpolarizing the heart, and slowing it down. K leaves, slowing down the heart bc it takes longer to reach threshold--- this antagonizes the Ca-mediated sympathetic action of NE What are the targets of cAMP? Either channels directly, or PKA 9which would phosphorylate target proteins) LECTURE 16 What are the excitatory amino acid NTs? L-glutamate and L-Aspartate What are 2 major ionotropic receptor types? AMPA & NMDA What is AMPA? Fast EPSP (think, we are AMPED up!), equipermeable to Na and K (reversal potential around 0 mV) What is NMDA? Slight depolarization removes intracellular Mg ion blockade, which allows Ca in (signal for potentiation); involved in the LTP in the hippocampus Where are AMPA and NMDA receptors found? Often times together. Activation of AMPA tiggers depolarization and subsequent activation of NMDA What does the Glutamate (AMPA, Kainate) receptor look like? 4 subunits (2 GluR1 and 2 GluR2) Each about 95 kDA with 3 membrane spanning units: glutamate binding residues at large extracellular domain What does the NMDA receptor look like? 2 subunits, NR1 and NR2 What types of receptors are important in LTP? NMDA How about for strokes? NMDA (Lazarides as the drug—it inhibits neuronal death) What is the difference between metabotropic and ionotropic receptors? Metabotropic activate G proteins, Ionotropic activate a specific ion channel How many metabotropic glutamate receptors are there? 3 different, anatomically separate types, both pre and post synaptic forms What is the “yang to the Glutamate system’s yin?” GABA—an inhibitory aa NT (fast!)—Glycine is a minor one Where is GABA found? In the CNS.. NOT the PNS Where is GABA synthesized? From L glutamate, via the GAD (via aa metabolism) What are the two GABA receptor types? GABAa: fast hyperpolarization via Cl channels: always slightly hyperpolarized compared with resting membrane potential GABA b: ENTIRELY different from a, much smaller signal, mediates slow hyperpolarization by opening K channelsà lead to presynaptic inhibition What is the agonist of GABAb? Baclofen: anti-spastic--- the reason we know about GABAb Where is GABAb found? Synaptic terminals, espec in the spinal cord GABA a? Fast, Cl GABA b? Slow, K What does the GABA a receptor look like? 5 subunits: alpha 1,2, beta 1, 2, and gamma Tell me about Ach. Synthesized from acetyl CoA and choline via choline Acyle Transferase (chat) How are synaptic actions terminated? (for Ach) Extracellular AchE What is the clinical significance of this? Antagonist of AchE is used as a treatment for MG Tell me about Ach receptors. 2 types, Muscarinic and Nicotonic Tell me about Nicotinic Ach receptors? Found in both the PNS and CNS: usually excitatory; equipermeable to Na and K Tell me about PNS Nicotinic Ach receptors In motorneurons to skeletal muscle, all autonomic ganglionic neurons (generates a fast EPSP) and some sympathetic post ganglionic neurons (to sweat glands) Ach is in? Pre-gang for para and sym; just post for sym Tell me about the structure of Ach Nicotinic receptors 5 subunits, Ach binding in the alpha subunit; all subunits needed for function Tell me about the muscarinic Ach receptors. Both in the PNS and CNS; may be excitatory or inhibitory; found on post ganglionic parasympathetic effector organs In the CNS, it is mostly inhibitory, opens the K channel Where are Nicotinic Ach receptors located in the CNS? Basal forebrain, and Renshaw cells of the spinal cord NIctonic? USUALLY EXCITATORY! Muscarinic? In the PNS: either one; in the CNS: usually inhibitory! What enzyme converts L-tyrosine into L-Dopa? Tyrosine hydroxylase What enzyme converts L-dopa into Dopamine? DOPA decarboxylase What enzyme converts Dopamine into Norepinephrine? Dopamine Beta Hydroxylase What enzyme converts norepinephrine into epinephrine? Phenylethanolamine N methyltransferase What are the catecholamines? Dopamine, Epinephrine, Norepinephrine How are the synaptic actions of these terminated? 1. Pre-synaptic uptake by Na ATPase 2. Enzyme degradation via MAO, intracellular in nerve terminal 3. Catechol-O-methyltransferase COMT, extracellular How is glutamate synthesized? Glutamate precursors How is it degraded? Pre-synaptic uptake How is GABA synthesized? From L-glutamate via GAD How is GABA degraded? Pre-synaptic reuptake, metabolized via Krebs Cycle How is NE synthesized? From dopamine, via dopamine beta hydroxylase How is NE degraded? One of the 3 ways catecholamines are (refer above) How is Epinephrine synthesized? From norepinephrine, via phenylethanolamine N methytransferase How is epi degraded? One of the three ways How is Ach synthesized? Acetyl CoA and chat How is it degraded? EXTRAcellular AchE How is Dopamine synthesized? From L-Dopa, via DOPA decarboxylase How is Serotonin Synthesized? Tryptophanà5 hydroxytrptophanàserotonin, using tryptophan hydroxylase and aromatic aa decarboxylase How is Serotonin degraded? Re-uptake specific transporters; (SSRI (Prozac)) Where is serotonin located? Raphe nucleus of midbrain reticular formation and enteric nervous system What are the Dopamine receptor types? D1 (excitatory) and D2&3 inhibitory via cAMP What are the 2 major neuronal groups for dopamine? Mesencephalic (subtantia nigram ventral tegmental system) and Lateral hypothalamus (tubule infundibulum) What is the function of the dopamine receptors? Nigrostriatal: motor planning/excecution; mesolimbinc: target oriented, motor behavior & prefrontal: high level sensory motor What are the serotonin receptors? 7 classes, 5-HT (1-7) they are all G-protein linked receptors Where are they located? Raphe nuclei of the midbrain What are the functions of Serotonin? Circadian rhythms, homeostasis, cerebral blood flow, and specific eating behaviors, sexual arousal and sleeping What are most migraine sufferers treated with? Sumitriptam Where is the principle location of histamine? Hypothalamus What are neuropeptides? They are synthesized from mRNA as large precursors, tissue specific processing. They are located diffusely in the hypothalamus, amygdale and NTS. They are co-released with other NTs, and have slow prolonged actions What is substance P? Nueropeptide, P for pain, associated with unmyelinated fibers, a NT of C pain fibers that terminated in the substantia gelatinosa of the anterior horn. Acts on mast cells in vicinity of injury and dialation, edema etc What is nitric oxide? Free radical gas, in the CNS: modulation of synaptic efficacy In the PNS: relaxes smooth muscle Where is NO synthesized from? L-arginine by nNOS, the synthesis is activated by Ca+ entry Where is NO released? LTP (hippocampus, NMDA mediated, post-synaptic) and LTD-cerebellum, pre-synaptic, down regulates glutamate receptors
LECTURE 17 How do you myelinate in the PNS? CNS? Schwann Cells, Oligodendrocytes What happens with acute cell injury (ischemia) Cell dies and turns red (red=dead); this is a sign of ischemic damage What is another name for glial cells? Astrocytes What do microglial cells do? Phagocytic, in the CNS as supporting cells, can proliferate and aggregate; neuronophagia if they eat neurons What are hereditofamilial diseases connected with? Metabolic diseases What is the function of glial cells? Support, stretch from ventricles to pia mater What holds together blood vessels in the brain, and forms part of the BBB? Glial cells What cell is defective in MS? Oligodendroglia What type of disease is MS? Inflammatory/Immunologic What is neurophil? Everything in between two cell bodies “fuzzy pink stuff” What would you find in the brain of a Parkinson’s patient? Lewy body What would you find in the brain of an alzheimer’s patient? Senile plaques, outside of the cell cytoplasm LECTURE 18 What is the neuromuscular unit? The motor unit consists of the lower motor neuron (located in the anterior horn of the spinal cord), the axon, and the muscle fibers that it innervates Where are the lower motor units that are innervating the proximal muscles, located in the anterior horn? Medially How about those motor neurons innervating the distal muscles? Lateral How about those that are used to flex? Extend? Flexion (motor pools) is dorsal, Extension is (ventral) What is the function of the motor end plate? NT release What is the function of the myocyte? Contracts and relaxes, muscle action What is paraneoplastic syndrome? Copies MG, where the motor end plate is affected, become weak What does ALS affect? The cell body with dendrites—affects lower and upper motor neurons What does polio or west nile affect? The cell body with dendrites How about Lambert-Eaton Syndrome? Motor End Plate (along with MG) What does leprosy do? Infects Schwann cells, demyelinates What is an example of an inflammatory neuronal disease? MS, segmental demyelination What do you call something with small, angulated fibers? Neurogenic Atrophy What is Guillain Barre Syndrome? Segmental Demyelination, where there is a dysfunction in the Schwann cell What do you think if you see fibrosis in a muscle? Myopathic process, NOT neurogenic process What is neurogenic atrophy? Withering away, bc no neuronal driveà there is no inflammation here What is myopthy/dystrophy? Incites the inflammatory process
LECTURE 19 Where are the spinal motor neurons located? VENTRAL horn (ventral gray)—Rexed’s laminae (VII-IX) What are renshaw cells? Inhibitory interneurons, found in the grey matter of the spinal cord, and associated (in 2 ways) with an alpha motor neuron. It uses Glycine as the inhibitory NT Where do the motor axons exit? Ventral root What is “motor pool”? All the neurons that control a muscle (i.e. the medial gastroc motor pool is 580 motor neurons) How are motor pools arranged? Organized in columns that may extend over several spinal segments; Proximal motor pools are medial in horn, distal pools are lateral in the horn; Flexor: dorsal; Extensor are ventral--- lots of overlap Will you find more synapses on proximal or distal dendrites? Proximal What is a motor unit? A motor neuron and all the muscle fibers that it innervates What are some electrophysiological Characteristics of Spinal Motor Neurons? LARGE somas, Fast APs, Dendritic Summation (excitatory and inhibitory inputs sum to determine if AP is initiated) What are the types of Motor Neurons? Alpha and Gamma What do ALPHA motor neurons innervate? Skeletal muscle What doe Gamma do? Innervate muscle spindle organs, smaller somas and axons than alphas What is the size principle? The smallest motor unit in a pool is activated first. As the strength of the contraction increases, larger motor units recruited What are the types of motor units? FAST: large motor neurons—faster velocity, innervate large number of fast contracting muscles that fatigue quickly SLOW: small motor neurons—slower conduction velocity, innervate smaller number of slow contracting muscles that fatigue slowly (postural muscles) Some muscles are a mixture of Fast and Slow What is the rationale for the Size Principle? Frees higher centers, supports precise, consistent control of contraction strength (motor units are added in roughly the same fraction of muscle force) What are extrafusal fibers? Intrafusal fibers? Extrafusal: regular muscle fibers; Intrafusal: muscle spindle organs, a sensory apparatus for monitoring muscle length What is the anatomy of skeletal muscle? Multinucleated muscle fibers, cisterns, T-tubles, SR, Filaments What is the anatomy of a myofibril? Sarcomere, Z disk, I and A bands What is the A band? Thin and Thick What is the I band? Thin (actin) only What is the Z disk? Adjacent sarcomeres butt up against one another here, where the thin filaments anchor themselves What is ATP needed for in the muscle contraction? To release myosin head from actin What is the purpose of the Sarcoplasmic Reticulum? Ca++ store, the enlargement of the smooth ER found in muscle cells on either side of the transverse tubules What are the t-tubules? Invaginations of the sarcolemma, into the cytoplasma of the muscle cell. What is needed to change the conformation of troponin, in order to expose the myosin binding site on actin? Calcium (released from the SR) What is the conformation of the myosin head when it binds to actin? It is cocked (with ADP + Pi attached) When can the myosin head exert contractile force? When it uncocks (and releases Pi and ADP) What happens to make myosin and actin release? ATP binds to the myosin head How does the myosin head restore to the cocked position? ATP is hydrolyzed to ADP + Pi Tell me about the Muscle Action Potential Nicotinic Ach receptors at the neuromuscular junction What is located at the T-tubules? Na, Ca, Ca+ activated K+channels, Voltage Gated Channels What manages the Ca+? Sarcoplasmic Reticulum—triggers contraction; there is a Ca-ATPase (also in the membrane) to remove Ca and relaxation What is resting length? The number of potential cross bridges, determines the force of contraction (when muscle at optimum length—there is the greatest possibility for myosin to bind to actin on Ca+ influx What is the difference between fused and unfused tetanus? Fused: muscle is totally contracted and can no longer generate new contractions; unfused: muscle is stuck in the contracted state, and can’t generate much more contraction What mediates muscle activity, making sure it stays within bounds, strength and control of contraction? Golgi tendons and muscle spindles What are muscle spindles? Sensory Organ measuring muscle length; Contractile at both ends, with a central non-contracting region that is sensory and sensitive to stretch What are the two types of spindle fibers? Nuclear Chain and Nuclear Bag fibers What are nuclear chain fibers? Short, slender, 2 or 3 per spindle What are nuclear bad fibers? Longer, thicker, typically 5 fibers per spindle What are Golgi tendon Organs? SIGNAL MUSCLE TENSION: Small encapsulated structures in tendons innervated by Type I beta afferents; when the muscle is stretched, 1 beta afferents increase the firing rate What is a phasic stretch receptor? Type Ia fibers (fast and adapt quickily) What is a tonic stretch receptor? Type II (slower to respond, but maintain their response to maintained stretch) What do tonic receptors respond to? Type II to LENGTH What do phasic receptors respond to? Type Ia respond to RATE of change How do phasic fibers (Ia) innervate motor neurons? Directly, (excitatory) or via Interneurons (inhibitory) How do tonic fibers (II) innervate motor neurons? ONLY via inhibitory neurons What are the two types of spindles? Type Ia and II, afferent axons (can measure length, in parallel with muscle) What are the tendon organs? In series, measure tension or force What is the “final common pathway?” Sherrington’s pathway
How are muscle spindles innervated? Gamma motor units How do the spindles signal their muscle length? By the discharge rate of their afferents (type Ia (usually bag) and II (usually chain)—there are sensitive to length, not force When the muscle shortens due to contraction, tension on spindle decreases, Ia and II afferents reduce the discharge rate bc muscle is no longer elongated and spindle is shortened LECTURE 20 What is alpha beta coactivation? Activate gamma motor neurons on the fly, in order to match the spindle length to the muscle length (retains spindle sensitivity because the Ia or II would be slack with a contracted muscle What is the myotatic stretch reflex? Typically activates type Ia (fast phasic) fibers and make excitatory synapse on alpha motor neuron, while making an inhibitory connection to antagonist muscles via Ia interneuron. Lengthen the muscle (by the tendon stretch or antagonist muscle contraction) and the stretched muscle will respond with a brief contraction What are the servomechanisms? Length: spindles Force: Golgi What is the flexion withdrawal reflex? Occurs when you’re suddenly step on something sharp--- retract the one leg, but contralateral extension of the other leg Withdraw one limb, and extend the other. All mediated by the spinal cord, not needing conscious intervention What is the golgi tendon organ reflex? When muscle contracts, Ib afferent interneuron will increase their discharge due to the increased tension. This inhibits further Ib interneurons, and makes the muscle relax to avoid further tension. This is a servomechanism to avoid avulsions! What is supraspinal control? What are the three classes of interneurons? Ia (spindle afferents) and Ib (Golgi, inhibit motor neurons of the same muscle), and also the Renshaw Cells (excited by motorneuron recurrent collaterals, inhibit motor neurons in the same pool) What are Renshaw cells? Excited by motor neurons, Feedback and inhibit by glycine to the same motor neuron and neurons in the same pool; so that it can damp down abrupt excitation by the muscles, to avoid muscle contractions being too brisk What are the four descending spinal tracts? Corticospinal tract, brainstem tracts of the pons &medulla, Tracts from tegmental pons and the midbrain tracts Where are the majority of the spinal afferents coming from? Direct, from supraspinal centers, or indirect via local interneurons Tell me about the Corticospinal Tract Excitatory, voluntary movements, distal extremeties What about the pons and medulla tracts? What about tegmental pons? Rubrospinal What is activated with novel stimuli? Locus Coerculus What is activated in the late afternoon, about ready for sleep? Raphe nucleus What distinguishes upper from lower motor neuron disease? LOWER: affects motorneurons or sensory input to LOCAL reflexes, whereas UPPER: affects central control of motor function, and you will see release inhibition What are some signs of upper motor disease? Weakness, paralysis, hyperreflexia, increased muscle tone and clonus What are some signs of lower motor disease? Weakness, paralysis, flaccidity, atrophy and fasciculations Why does the babinski’s sign occur in infants? The coricospinal tract is not fully myelinated yet; + sign is dorsiflexion; a fairly sure sign of upper motorneuron disease in non-neonates LECTURE 21 What are encapsulated receptors? Include meissner and merkel, used to detect edges (good for brail reading) What are pacinian corpuslces? Sense vibration What are muscle spindles? Sense muscle length and how far it’s been stretched What are golgi tendon organs? Sense muscle tension What are free nerve endings? Pain/temp What are Ruffini organs? Pressure, joint position What are nuclear chain fibers? The functional signal is length and tension, type II fibers What are nuclear bag fibers? Type Ia, fast, phasic, length, rate of change, velocity What are Group A delta high threshold mechanoreceptors responsible for? Group C? A: intial stimulus of sharp pain whereas Group C has delayed onset but lasts over time Why do we think cool mint? There is an interplay between chemical and thermal receptors where thermal receptors are dependent on the presence and concentrations of chemicals--- perceived temperature change Where do the fibers of pain and temp go as they ascend the spinal cord? Move to contralateral side by the medulla Where do the large fibers of two point discrimination and proprioception go as they travel up the spinal cord? Ipsilateral, go to the medulla directly How do phantom pains work? The peripheral nerve is maintained, even if the limb is no longer there. Example: the DRG of the dermatomes are maintained and these continue to send signals to the somatosensory cortex, giving the sensation of a missing limb How does referred pain work? Example: C3,4,5 keep your diaphragm alive provides the motor fibers going to your diaphragm and also the sensory for your shoulder. Similarly, your heart is innervated by T1-4 nerves, which provide sensory to your left arm (precisely at the dermatome innervated at T1) Basically, the visceral afferents mismatch at the level of the spinal cord and will have cross connections to the somatofibers and are thus reflected back to the somatosensory cortex as referred pain What are the mechanoreceptor fiber types? ALL of them are ABeta LECTURE 22 What are the symptoms of sensory Peripheral Nerve Damage? Numbness, decreased sensation, allodynia (pain from light touch) and paresthesias (pins and needles) What are the symptoms from PNS motor damage? Weakness, atrophy, decreased reflexes, fasiculations (visible muscle twitching) What are the symptoms of autonomic PNS damage? Lightheadedness (after standing from sitting) altered sweating, incontinence, sex dysfunction, papillary abnormalities What’s the most important test for the PNS? The clinical exam, but EMG can show denervation in the muscles and MRI can look for herniations What is Guillian Barre Syndrome? Polyradiculopathy, ascending paralysis--- autonomic, sensory damage. Demyelination What is the treatment for GB? Manage symptoms, make sure they are breathing J What disorders are associated with the neuromuscular junction? Lambert-Easton Myasthenic Syndrome and MG What are EMG/NCS used for? To confirm a diagnosis and rate severity (mild, moderate, severe) and acuity (acute, subacute, chronic), Acuity will make a difference bc chronic=no operation What to order? Mononeuropathy: (carpal tunnel) order NCS/EMG on BOTH hands to compare Peripheral Neuropathy: order NCS/EMG on the most symptomatic side (left upper and lower) Radiculopathy: only the affected limb needs to be studied ALS: a 3-5 limb needs to be studied LECTURE 23 What is the subcostal nerve? T12 C2: most of the head C3,4,5 keep the diaphragm alive C5: shoulder abduction/dermatome-àmajor sensory to the face C6: wrist extension 1st and 2nd phalanges, lateral arm C5-6: Biceps reflex C7: middle finger dermatome, Triceps reflex C8: 4th and 5th dermatome DISORDERS Waiter’s Tip? C5-C6 (Erb Duchenne) Klumpke’s Palsy (associated with Horner’s Syndrome) C8-T1 Ulnar Nerve Palsy? C8-T1 Thoracic Outlet Syndrome? C8-T1 What must you worry about if you have a damage at C8/T1? Klumpke’s Palsy (Horner’s associated) Ulnar Nerve Palsy Thoracic Outlet Syndrome T4-T5: nipple area T10: umbilicus S1: Achilles, plantar flexion and the little toe L1-2: cremasteric reflex L4: patellar reflex L2,3,4 keep YOU off the floor (obturator and femoral nerves) L4-S2: sciatic nerve and branches L5: anterolateral shin and BIG TOE
Most herniations occur in the cervical or lumbar region, hardly any in the thoracic What are the most common lumbosacral radiculopathies? L5-S1 Where does the nucleus pulposus arise embryologically? Notochord, NOT NEURAL CREST What is Pancoast’s tumor? Flat little tumor in the apical portion of the lung that can invade sympathetic and get into the lower part of the brachial plexus Achilles S1 Patellar L4 Cremaster L1-2 Anal Wink S2,3,4 and S5 Middle Finger C7 Wrist Extension C6 Biceps Contraction C5-6 Nipples T4 Big Toe L5 Little toe S1 Femoral/Obturator L2,3,4 Triceps C7 Waiter’s Tip C5-6 Anterior Shin L5 Cauda Equina S2-5 Pudendal Area S2-5
LECTURE 24 What is the corticospinal tract? Allows precise, discrete, voluntary mvmts; DECUSSATES in the medullary pyramids, starts in the pre-central gyrus, internal capsule, cerebral peduncle, pyramid, cross above the foramen of monro….to the other side in the lateral Corticospinal T. What happens if you lesion the corticospinal tract on the left side? You get ipsilateral paralysis, distal to the lesion What controls the sympathetic? Hypothalamus What happens in horner’s syndrome? Ipsilateral sympathetic innervations is disrupted for the face What controls bladder sensation? ALS (spinothalamic—for the bladder wall) and Dorsal Column Pathway (urethral) Where does this sensory info travel? Pontine Micturition Center (urinary reflex) and to the sensory cortex (post-central gyrus) where you sense urge to pee Where does the info go from the post central gyrus? To the INHIBITING area (frontal micturition) which will stop the pee from leaking down your leg So, how do you go pee? Output from your frontal micturation area travels down the corticospinal tract to the sacral level, parasymp nerves that can release sphincters allows the detrusser to contract for urination to occur Babies have their pontine micturation center continually stimulated bc their frontal micturition axons are not yet myelinated No control for peeing Parasympathetic Neurons from the anterior horn of the sacral spine are responsible for? Can cause relaxation of the sphincters and pelvic floor muscles What happens with lesions in the frontal micturation area? No willful control of urination, causes trauma, hydrocephalus What happens with a lesion in the spinal cord or medulla (pontine micturation, reflex area, cannot release urine) At first, bladder won’t contract (FLACCID), therefore you will only leak urine.. but weeks later experience spasticity (hyperreflexive) due to prolonged distension What happens with a peripheral lesion or a spinal cord (S2-4) lesion? Flaccid bladder due to loss of parasympathetics--- overflow incontinence What is wallerian degeneration? Cut axon, the axon distal will degenerate, but up until the cut, the axon is fine LECTURE 25 What are the 4 ALS tracts? 1. Spinothalamic 2. Spinoreticular 3. Spinotectal 4. Central sympathetic tract (motor) What are the principle sensory tracts? Dorsal/posterior colums (fine touch/proprioception) Dorsal and ventral spinocerebellar tract (fine touch/proprioception) ALS Tell me about the spinothalamic tract? The fibers cross IMMEDIATELY (with 2-3 segments) to the other side before ascending: THIS IS WHY WE HAVE CONTRALATERAL PAIN AND TEMP! How do we get Horner’s syndrome? Lesion of the spinothalamic tract---ALS lesion What happens with a lesion on one side of the spinal cord? Fine touch, vibration, proprioception lost ipsilaterally and pain and temp lost contralaterally What does the dorsal or posterior column sense? Fine touch and proprioception What does the dorsal spinocerebellar tract sense? Fine touch and proprioception What does the ventral spinocerebellar tract sense? Fine touch and proprioception How does the dorsal column pathway get from the medullary nucleus (gracilis or cuneatus) to the medial lemniscus? Internal Arcuate Fibers Where does it go from the medial lemniscus? To the VPL in the thalamus How does it get to the post-central gyrus? Internal Capsule What does the spinothalamic tract sense? Pain and Tempterature What is of concern with an ACA infarct? Legs How about an MCA infarct? Arms and face Where would you see more white matter—cervical or lumbar? Cervical What is needed to stand up straight? Visual input, vestibular system for balance, proprioception What is the romberg test? Telling the patient to stand up with their eyes closed to determine if something is wrong What is a syringomyelia? Small cyst in the spinal canal; first press on the bilateral crossing spinothalamic fibers—therefore have bilateral problem Which is more lateral ina spinal cross section, pain and temp or fine touch/proprioception? Pain and Temp; enter through the lissauer’s tract
LECTURE 28 What are the boundaries of the posterior fossa? Petrous part of the temporal bone, foramen magnum, dorsum sellae What is the brainstem? Medulla oblongata, pons and midbrain What is the anterior boundary btween the diencephalon and the midbrain? Draw a line from the mamillary bodies to the posterior commissure What is the pyrimidal tract? Corticospinal tract What cranial nerve comes out dorsally? CN IV What cranial nerve is immediately caudal to the mamillary bodies?
Name the foramina that each CN exit the skull CN1 Cribiform plate CN2 Optic canal CN3 Superior Orbital Fissure CN4 Superior Orbital Fissure CN5 V1: Superior Orbital Fissure; V2: Rotundum; V3: Ovale CN6 Superior Orbital Fissure CN7 Auditory Canal (stylomastoid foramen) CN8: Auditory Canal CN9: Jugular Foramen CN10 Jugular Foramen CN11 Jugular Foramen (enters the skull via foramen magnum) CN12 Hypoglossal Foramen
How many CN exit the jugular foramen? 3 How many CN exit the superior orbital fissure? 3,4,5-1, 6 (total of 4) How many exit the auditory canal? 2
Give me the functional categories of each of the CN, and their functions.
CNI Special Somatic Sensory: Olfaction CNII Special Somatic Sensory: Vision CNIII Somatic Motor—levator palprebral superior and all extraocular muscles except SO4 and LR6 Parasympathetic—pupil constrictoer and ciliary muscles (for near vision) CNIV Somatic Motor—SO causes depression and intorsion of the eye CNV General Somatic Sensory—sensation of touch, pain, temp, proprioception, vibration for face, mouth ant 2/3 of tongue, nasal sinuses and meninges Branchial Motor—muscles of mastication and tensor tympani CNVI Somatic Motor—lateral rectus, abducts the eye CNVII Branchial Motor—facial expression, stapedius, and part of digastrics Parasympathetic—lacrimal gland, and to submax, submandibular, and other salivary except the parotid Visceral Sensory—taste from the anterior 2/3 of tongue General Somatic Sensory—sense from small region of the ext. aud meatus CNVIII Special Somatic Sensory: Hearing and vestibular sensation CNIX Branchial Motor—stylopharyngeus Para—parotid gland General Somatic Sensory—sensation from middle ear, region near the ext aud meatus, pharynx, posterior 1/3 tongue Visceral Sensory (special)—taste from posterior third of the tongue Visceral Sensory (general)—chemo and baro receptors from the carotid body CNX Branchial Motor—pharyngeal muscles (swallow) and laryngeal muscles (voice box) Parasympathetic—to heart, lungs, digestive tract down to the splenic flexure General Somatic Sensory—sensation from the pharynx, meninges, and small region near ext aud meatus Visceral Sensation (special)—taste from epiglottis and pharynx Visceral Sensation (general)—chemo and baro- receptors from the aortic arch CNXI Branchial Motor: SCM and upper traps CNXII Somatic Motor: intrinsic muscle of the tongue NUCLEI OF THE BRAINSTEM What are the brainstem nuclei for the somatic motor? III Oculomotor IV Trochlear VI Abducens XII Hypoglossal What are the brainstem nuclei for branchial motor? V motor nucleus for V VII Facial Nucleus IX, X Nucleus Ambiguus XI Accessory Spinal nucleus What are the brainstem nuclei for parasympathetics? III Edinger-Westphal nucleus VII Superior Salivatory IX Inferior Salivatory X Dorsal Motor nucleus of X What are the brainstem nuclei for Special Somatic Sensory? VIII Cochlear Nuclei & Vestibular nuclei What are the brainstem nuclei for General Somatic Sensory? (touch, pain, vibration, proprioception for face, sinuses and meninges) V, VII, IX, X: Trigeminal Nuclei What are the brainstem nuclei for special visceral sensory? VII, IX, X: nucleus solitarius (soli-tastius) for TASTE (rostral portion, gustatory nucleus) What are the brainstem nuclei for general visceral sensory? IX & X: nucleus solitarius (caudal portion, cardiovascular nucleus) Name the CN that correspond with each classification Somatic Motor III, IV, VI, XII, Branchial Motor V, VII, IX, X, XI Parasympathetic Motor III, VII, IX, X Visceral Sensory (SPECIAL AFFERENT) VII, IX, X Visceral Sensory (GENERAL AFFERENT) IX, X,
LECTURE 30 What vestibules contain perilymph? Scala tympani and scala vestibule What vestibules contain endolymph? Scala media What does perilymph resemble? CSF: Extra-cellular fluid—high Na+ concentration What does endolymph resemble? Intra-cellular fluid—high in K+-- found in scala media What does Stria Vascularis do? Makes endolymph and generates small, +90mV—heavy energy consumer; uses Na+K+ pumps What can high frequency sounds stimulate? The base of the basilar membrane---not the apical part What can low frequeny sounds stimulate? The apical part of the basilar membrane, and slight stimulation of the basal part What does loudness perceive? The intensity (the amplitude of the sound wave, transmitted to the tympanic membrane) What does pitch perceive? Frequency—the number of cylces per second, measured in Hz What is the function of the middle ear? Impedence matching (transmitting waves travelling through air to that in fluid, make sure that the vibrations are absorbed, and not reflected—w/out the middle ear, loss of 30dB) How does the middle ear achieve this impedence matching? The small area between the stapes and the tympanic membrane & the lever action of the ossicles amplifies the pressure at the footplate of the stapes What is the function of the OHC? Stimulated from the basilar membrane--It’s motility contributes to the mechanical amplification of the IHC of the cochlea How does the cochlea analyze sound? By it’s pitch.. by registering the relative frequencies of the basilar membrane (the apical portion of the cochlea is the skinniest, and it activated by low pitch sound. Low pitch sound can activate both the basal part (sorta) and the apical part, but the high frequency sounds can only activate the basal part What is Meniere’s Disease? An ENT’s nightmare: sporadic vertigo, tinnitus, low frequency HL. Usually unilateral—associated with endolymphatic hydrops (swelling of the scala media) What are otoacoustic emissions? Used to screen newborns’ hearing—manipulates the active process of the cochlear amplifier, which tests the integrity of the OHC particularly (language is acquired in the first 2 years of life) What are cochlear implants used for? Sensineural HL that can’t be helped with hearing aids. There are no hair cells left. Multiple electrodes are inserted into scala tympani, and stimulate the VIII nerve dendrites What is a good way to test if hearing loss has central components? (like seen in PD, MS, or just aging)—competing message tests (cocktail party effect) What is tone stimulus? Single frequency (pure tone), tests one cochlea place What is click stimulus? Brief, contains energy at all frequencies, and tests the whole cochlea What is a pip? Tone burst, that is a compromise: reasonable frequency-specific, but brief enough to evoke a scalp potential What is an audiometry? Seen in trent quinlan’s office. Test hearing threshold of tone pips What is the auditory evoked potential? Present click or short tone burst, average vertex response--- largely origin in the high frequency basal turn of the cochlea What is a good test for a suspected high frequency hearing loss? AEP (can be done while unconscious) What is a good test for suspected conductive hearing loss? Impedance audiometry—should get a contralateral reflex What do low frequency sounds stimulate? The apical portion of the basilar membrane (can do the basal part) What do high frequency? Basal part What neurotransmitter is used by Hair cells? Glutamate What is the source of the cochlear amplifier? OHC What is CF? Characteristic frequency—of the basilar membrane LECTURE 33 What are the criteria for a cochlear implant candidate? 3-6 month trial with hearing aid doesn’t afford any benefit, age of implantation 12-18 for profound, more than 18 for severe to profound loss; no medical contraindications; education focusing on auditory-oral skills What are the four types of hearing loss? Sensorineural, Conductance, Mixed and Auditory Dysynchrony What is auditory dysynchrony? Cochlear is fine, but either the nerve or the connection to the nerve is damaged What are the types of hearing tests? Objective (no response) and behavioral (need response) What is the ABR? Auditory brainstem response that assesses the function of the cochlea up to the lower brainstem by measuring the electrical potential that occurs to an auditory response What is the range of thresholds for mild hearing loss? 26-45 dB Moderate? 46-65dB Severe 66-85dB Profound? 86dB or higher What is a good way to distinguish conductive vs sensorineural hearing loss? AC vs BC tests—if both are screwed up, mixed LECTURE 34
LAB QUESTIONS: What is the word to “cross over”? Decussate What is the big difference between rostral and caudal medulla? Rostral medulla has the inferior olivary nucleus that looks all squiggly—laterally expanded What is the pathway for the Dorsal Medial Leminiscus? For the legs: below T6—receptorà the dorsal root ganglion, enters into the fasciculus gracilis on the dorsal feniculus , ascends ipsilaterally and terminates at the nucleus gracilis (of the caudal medulla), then the new axon decussates through the internal arcuate fibers that move downward and medially before turning rostrally to become the medial lemniscus fibers. The medial lemniscus sit on top of the medually pyramids, it terminates in the VPL of the thalamus, the third axon travels to the somatosensory cortex, at the postcentral gyrus (very medial) What is the pathway for the DML from the arms? Above T6—through the DRG, into the cuneatus tract, ascending and synapsing in the caudal medulla at the cuneatus nucleus before decussating through the interal arcuate fibers, down and medial to the medial leminiscus before ascending to the VPL of the thalamus, and sending fibers to the somatosensory cortex ala postcentral gyrus What does the dorsal medial lemiscus carry? Sensory fibers containing information on fine touch and proprioception What happens with transection above the caudal medulla (above the sensory decussation)? Contralateral loss of the DML What happens with transection below, in the spinal cord? Ipsilateral loss of the DML What is the function of the lateral spinothalamic tract? Mediates pain and temperature (ALS tract) What are the ALS receptors? Free nerve endings (from both fast and slow-conducting pain fibers (A-delta and C) Where are the first order neurons of the ALS found? Dorsal root ganglia of all levels, projecting axons to the spinal cord through Lissauer’s tract to second order neurons Where do the second order neurons go, from the Lissauer’s tract? Through the ventral white commissure (aka they decussate IMMEDIAMENTE!) and the ALS ascends via the contralateral lateral funiculus. Their axons terminate in VPL of the thalamus, and then project to the somatosensory cortex What happens with transection of the ALS? Contralateral loss of pain and temp What about the lateral corticospinal tract? It mediates controlled, voluntary skilled motor activity, primarily of the upper limbs (it isn’t fully myelinated until end of 2nd year—Babinski’s sign) Where is the origin of the corticospinal tracts? It arises from layer V of the cortex, from three motor areas (premotor, primary, primary sensory cortex and the arm, face and foot areas) Where does the corticospinal tract terminate? Contralaterally, through interneurons or ventral horn motor neurons Where does the lateral corticospinal tract run? In the dorsal part of the lateral funiculus (once it gets to the brainstem, moves ventral!) Where does the corticospinal tract decussate? At the medullary pyramids! What happens with a transection of the corticospinal tract, BELOW the medulla? Ipsilateral spastic paresis and babinski’s sign What happens with a transection of the corticospinal tract, ABOVE the medulla? Contralateral spastic paresis and babinski’s sign What is the deal with Horner’s Syndrome? Interruption of the hypothalamospinal tract—which runs w/o interruption from the hypothalamus to the ciliospinal center of the IML-à sympathetic chain What does the ALS carry? Information that originates in the spinal cord that transmits info to the thalamus about pain and temp What is the ALS? Consists of multiple tracts including the anterior, lateral and ventral spinothalamic tracts, spinotectal and spinoreticular tract Where does the crossover occur in the ALS system? In the SPINAL cord, not the brainstem Where does the crossover occur in the DML system? At the level of the (caudal) medulla—in the brainstem Where do the neurons synapse in the ALS system? Thalamus How about the medial leminscus fibers? YES Tell me about the dorsal spinocerebellar tract Axon fibers carry proprioception information about joint and limb position to the cerebellum. The fibers run superficially in the lateral funiculus, and arise from cells in the ipsilateral Clarke’s nucleus Tell me about the corticospinal system? Voluntary motor system, collection of axons from the cerebral cortex of brain o the spinal cord. There are two tracts, lateral and ventral, that travel together, ipsilateral to their origin in the medullary pyramids What is corticobulbar? Send information from the cortex to the cranial nerve nuclei What is Clarke’s nucleus? C8-L3 and give rise to the dorsal spinocerebellar tract What is the function of the dorsal medial column leminscus? Mediates tactile discrimination, vibration, form recognition and conscious proprioception What are the DML receptors? Pacinian and meissner’s tactile corpuscles, joint receptors, muscle spindles and golgi tendon organs ALS—where do you terminate? VPL of the thalamusà heading to cortex! Tell me about UMN lesions. Caused by transection of the corticospinal tract, or destruction of the cortical cells of origin, result in spastic paresis/ B.Sign Tell me about LMN lesions. These are caused by damage to the motor neurons, resulting in flaccid paralysis, absent reflexes, atrophy, fasciculations, and fibrillations
SPINAL LESION FUNCTION LOSS Lateral corticospinal motor ipsilateral spastic paresis w/ pyramidal signs Lateral Spinothalamic pain & temp Contralateral loss P&T, one segment below lesion Gracile/Cuneate Fasiculus FT, Prop, Vibration Ipsilateral loss of FT, Prop, Vib from legs/arms Dorsal Horn ---anesthesia & arreflexia---- Ventral White Commissure ---Pain & Temp transmission impulses bilaterally through involved dermatomes
What is an example of a combined UMN and LMN? ALS (amyotrophic lateral sclerosis) or lou gehrig’s disease—damage to the corticospinal tract w/ pyramidal signs (b.s.) no sensory deficits Where do you see the superior colliculus in the midbrain? When you can see What is the trigeminothalamic pathway? VENTRAL: pain and temp sensation from the face and oral cavity DORSAL: tactile discrimination and pressure sensation from face and oral cavity
AUDITORY SYSTEM How is sound transmitted to the brain? The hair cells of corti (innervated by the peripheral processes of bipolar cells of the spiral ganglion). They are stimulated by vibrations of the basilar membrane—IHC are the chief sensory elements, and synapse with myelinated cochlear VIII neurons. The OHC synapse with unmyelinated neurons of cochlear VIII nerveà project to the cochlear nucleiàsuperior olivary nucleusàlateral leminscusànucleus of the inferior colliculusà medial geniculateàvia internal capsuleàtransverse gyrus of the temporal lobe
THALAMUS
Anterior Nucleus: (AN) Receives input from the mamillary nucleus through the mamillothalamic tractà project to the CINGULATE GYRUS Medio-dorsal Nucleus (MD) Reciprocally connected to the pre-frontal cortex Receives input from the amygdala, substantia nigra, and temporal neocortex DESTRUCTION results in memory loss; needed for expression of affect, emotion and behavior Ventral Anterior FROM: globus pallidus and substantia nigra TO: diffuse frontal cortex Ventral Lateral FROM: dentate nucleus, globus pallidue, substantia nigra TO: motor cortex Ventral Posterior Lateral FROM the DML (medial leminscus) and the spinothalamic tracts TO: Somatosensory cortex (everywhere but face) Ventral Posterior Medial FROM: trigeminothalamic tracts TO: somatosensory and taste cortex Intralaminar Nucleus Recieves info from the globus pallidus and projects to the caudate nucleus and putamen (collectively known as striatum) Pulvinar Reciprocal connections with association cortex of the occipital, parietal and posterior temporal lobes What is the metathalamus? The medial and lateral geniculates What is the reticular nucleus of thalamus? It surrounds the thalamus as a thin layer of GABA neurons, receives excitatory collateral input from the corticothalamic and thalamocortical fibers, and then has inhibitory fibers back to the thalamus from where it received the input What is the epithalamus region? contains the pineal gland-most clinically significant portionàA tumor or calcification here will press on the superior colliculus and pre-tectal area, this will lead to a loss of upward gaze movement
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