block 5 week 1

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block 5 week 1
2011-05-28 20:42:26

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  1. MAPs
    • microtubule-associated proteins
    • MAP-1 and -5 found throughout the neuron
    • MAP-2 specific for dendrites
  2. postsynaptic specializations
    • dendrite membranes w/ receptors and gap jx
    • In the CNS, spines are specializations
  3. axon hillock & terminal bouton
    • axon hillock: aka "initial segment"
    • w/o Nissl bodies
    • unmyelinated, initiation of APs
    • terminal bouton: aka end bulb/axon terminal
    • specialized to convert electrical signals to release of neurotransmitters
  4. Axon features
    • cytoplasm: sER, mitochondria, vesicles, actin filaments, intermediate (neuro-) filaments, microtubules, MAP1,3,5, motoric proteins that mediate transport of vesicles along axona
    • motoric proteins: kinesin moves vesicles towards + end of microtubules in anterograde transport; dynein moves vesicles toward - end in retrograde transport
  5. unipolar neurons
    • single process
    • only during development
  6. bipolar neurons
    • 2 processes
    • olfactory epithelium
    • vestibular and cochlear ganglia
  7. pseudounipolar neurons
    • only one process divided into a central and peripheral branch
    • sensory, DRG
    • when you take a DRG neuron and put into culture, it will become multipolar
  8. multipolar neurons
    • most common
    • eg pyramidal cells, motor neurons, interneurons
  9. classes of neurons based on function
    • sensory/afferent neurons: primarily in the PNS, in CNS as retinal ganglion cells
    • motor/efferent neurons: originate in CNS
    • interneurons: in CNS, higher order functions like memory and learning
  10. ALS
    • Amyotrophic lateral sclerosis: progressive motoneuron disease
    • aka Lou Gehrig's
    • presenting w/ weakness in affected limb, leads to death from severe paralysis of respiratory system
  11. classification based on chemistry
    • acetylcholinergic: motoneurons
    • dopaminergic: substantia nigra neurons that use DA as a neurotransmitter
    • excitatory and inhibitory AA neurons: glutamate + (round vesicles), GABA - (flattened vesicles)
    • peptidergic: enkephalins, substance P, CCK, CGRP, etc
  12. astrocytes
    • found in white and gray matter
    • glial fibrillary acidic protein (GFAP)
    • end feet cover outer surface of blood vessels, role in BBB
    • Regulation of [ionic], [neurotransmitter], uptake of neurotrans.
  13. types of astrocytes
    • protoplasmic: gray matter
    • fibrous: white matter
    • reactive: activated by injury, formation of glial scar (eg infarction, multiple sclerosis, infection), "astrogliosis/gliosis"
  14. oligodendrocytes
    • myelin of CNS
    • can cover up to 10 axons
    • most myelination occurs post-embryonically
    • fewer Schmidt-Lanterman clefts, no basal lamina in the CNS
  15. Multiple sclerosis
    • demyelinating disease, autoimmune
    • T cells -> Fas ligand -> apoptosis of oligodendrocytes
    • Macrophages strip myelin from axons
    • plaques of astrocytic aggregations
  16. microglia
    • macrophages of CNS: small cells w/long processes
    • involved in Alzheimer's, dementia, MS, ALS
  17. ependymal cells
    • line brain ventricles and central canal of spinal cord
    • form ependyma - cuboidal/low columnar, ciliated continous sheet
  18. choroid plexus
    • site of formation of CSF from blood
    • formed by evagination of pia and ependymal layers into ventricular spaces
  19. Schwann cells
    • cover axons w/ myelinated or unmyelinated coverings
    • flattened w/ flattened nucleus, some polysomes, rER, small Golgi, few mitochondria
    • nodes of Ranvier: interface between two myelin sheaths (internode) made by separate Schwann cell
    • internodal myelin sheath: cone-shaped, oblique Schmidt-Lanterman clefts/incisures, channel of communication from outside of myelin to the interior
  20. Satellite cells
    • found in sensory ganglia (DRG) and autonomic ganglia
    • multipotent glial cells
    • transdifferentiate into oligodendrocytes, Schwann cells, astrocytes
    • provide support to neuronal cell bodies but don't form myelin
  21. gray matter v. white matter
    • high concentration of cell bodies v. myelinated axons (high fat content)
    • cell bodies: nuclei, cortexes
    • axons: column, fasciculus, lemniscus, capsule, peduncle (afferents, efferents)
    • if axons have a common origin, course, and termination = tract/pathway
  22. brain stem
    • medulla, pons, midbrain
    • multiple pathways, cranial nerve nuclei III-XII
  23. cerebellum
    • cerebellar cortex, deep cerebellar nuclei, connections to brainstem (cerebellar peduncles)
    • Purkinje cells w/massive dendrites
    • deficits in balance, coordination
  24. basal ganglia
    • w/in cerebral hemisphere, associated w/motor control, planning
    • caudate, putamen, globus pallidus
    • related structures: substantia nigra, subthalamic nucleus
    • movements disorders, Huntington's and Parkinson's
  25. diencephalon
    thalamus, hypothalamus, subthalamus, epithalamus
  26. thalamus
    • multiple nuclei, form 2 egg-shaped structures on each side of midline
    • process info, send to cerebral cortex, which also projects back to thalamus
  27. hippocampus
    • limbic system (also includes amygdala)
    • deep in temporal lobe
    • consolidation of short-term -> long-term memory
    • affected in temporal lobe epilepsy, Alzheimer's disease
  28. end-plate
    • neuromuscular junction
    • site of contact between motor neuron and skeletal muscle fiber
    • synaptic boutons release ACh, postsynaptic muscle fiber has junctional folds adjacent, separated by synaptic cleft containing basement membrane (synaptic basal lamina) w/ collagen, ECM proteins, and AChE
    • synaptic vesicles cluster in active zones
  29. synaptic transmission @ neuromuscular jx
    • depolarization -> voltage-sensitive Ca++ channel influx -> fusion of ACh synaptic vesicles w/presynaptic membrane via v(esicle)-SNAREs/synaptobrevin and t(arget)-SNAREs, quantal release
    • SNARE: SNAP receptors, syntaxin and SNAP-25 found @ synapses
    • complexin: SNARE-interacting protein that stops release until there is a signal
    • synaptotagmin: drives complexin off of the vesicle so that fusion can complete
  30. tetanus toxin, botulinum toxin mech of action
    • cleave synaptobrevin
    • (some botulinum toxin cleaves syntaxin, SNAP-25)
  31. facilitation and depression
    • facilitation: during short burst of presynaptic APs, EPPs progressively increase in amplitude (due to addition of "residual Ca++"
    • depression: prolonged burst of presynaptic APs, size of EPPs declines (due to fewer available vesicles)
    • If neuromuscular jx has a lower safety factor, synaptic transmission rapidly declines (myasthenia gravis)
  32. curare, alpha-bungarotoxin
    • partially block postsynaptic ACh receptors
    • highly polar, poor PO bioavail
  33. I = g(Vm – Erev)
    • g: membrane conductance (# of open channels)
    • (Vm – Erev): difference between membrane potential and equilibrium potential, aka driving force
    • at rest, membrane potential Vm ~ Ek
  34. Wallerian degeneration
    • when axon is cut/crushed, axon distal to injury site undergoes active degeneration
    • activation of degradative enzymes like calpain -> balling up of myelin into myelin ovoids
    • proximal cell body undergoes chromolysis, possible apoptosis
    • proximal axon stump starts sprouting
    • distal Schwann cells proliferate to form a tube (Bunger's band) to guide the sprout (thinly myelinated as it regenerates)
    • crush injury: basal lamina and perineurium may still be intact, easier regeneration
  35. epineurium
    • loose connective tissue seath, collagen, fibroblasts, mast cells, blood vessels
    • tensile strength of nerves
  36. perineurium
    • encloses nerve fascicles, concentric layers/sleeves of endothelial cells w/ tight jx, collagen between layers
    • blood-nerve barrier
  37. endoneurium
    • innermost layer
    • collagen fibers adjacent to Schwann cells
  38. latrotoxin
    • black widow spider
    • massive spontaneous release @ NMJ
    • Histo: swollen bouton, depleted of vesicles
    • synaptic transmission then shut down
  39. safety factor/margin
    • amount above threshold
    • variability in amplitude, content of vesicles
  40. compound action potential
    • characteristics of waveform don't change, other than amplitude
    • 1-alpha motor neuron response is measured
  41. paranodes
    • high concentration of K+ channels
    • CASPR2: help Na+ channels get to correct spot on the membrane
  42. what are the fastest nerve fibers?
    • large and myelinated
    • major afferent: proprioception, muscle spindle, Golgi tendon organ
    • major efferent: motor neurons
  43. what are the slowest nerve fibers?
    slow pain, heat, itch (C fibers)
  44. axonal degeneration proximal and distal stimulation
    proximal and distal: reduced amplitude
  45. conduction block proximal and distal stimulation
    • proximal: reduced amplitude
    • distal: normal
  46. local demyelination proximal and distal stimulation
    • proximal: slow
    • distal: normal
  47. succinylcholine
    • non-competitive antagonist
    • 2 ACh molecules fused together
    • only metabolized by pseudoAChE
    • short onset and duration, for intubation
    • depolarizing antagonist: opens channels, fasciculations and contractions prior to flaccid paralysis
    • Phase I (can't repolarize) v. II block
    • SE: hyperkalemia, incr. IOP, incr. intragastric pressure
  48. dantrolene
    • spasmolytic drug
    • binds RyR, blocks Ca++ release
    • can treat malignant hyperthermia after anesthesia
  49. diazepam v. baclofen
    GABA-A (ligand-gated Cl- channel) v. GABA-B (GPCR, incr. conductance of K+ channel, inhibition of cAMP)
  50. Lambert-Eaton Myasthenic Syndrome (LEM)
    • presynaptic
    • decreased release of ACh due to Ab against Ca++ channel
    • muscle weakness
  51. Myasthenia gravis
    • diplopia, ptosis, later extends to limbs
    • worse w/exertion, throughout day
    • Ab against nicotinic receptors postsynaptically
  52. Myasthenia gravis treatments
    • AChEI's: pyridostigmine, neostigmine 3-6h
    • corticosteriods: prednisone, moderate-severe cases
    • immunosupressants: azathioprine, inhibitor of DNA/RNA synth, slow action
    • IVIG: several months duration
    • Plasmapheresis: 6-8wk duration
    • Thymectomy: 75% pts w/MG have abnormalities
  53. Guillian-Barre Syndrome
    • progressive muscle weakness
    • deep tendon reflexes absent
  54. locus ceruleus, raphe nuclei, ventral tegmental area
    noradrengeric, serotoregic, dopaminergic
  55. Ia v Ib fibers
    • Ia = assoc w/muscle spindle, largest and fastest
    • Ib = assoc w/Golgi tendon organ
  56. zones of cerebellum