Lecture 10

CSB332H1S L10; Feb. 13, 2012  Most often synapse becomes weakened Degeneration & Regeneration o Either due to decrease in amt of transmitter released or in Read: Ch 27 the density of postsynaptic recs  Retrograde signals cause many presynaptic terminals to retract  If neuron regenerates & re-innervates target  synaptic inputs recover  Degeneration happens when have neural injury  Need degeneration before regeneration  The neuron synapsing onto the motoneuron & its target are also affected  Wallerian degeneration: o Characteristic seq of events following severing of a vertebrate peripheral nerve  Injury/Lesion  Distal axon degenerates o Schwann cells (had formed myelin sheath) dedifferentiate, Recording from muscle fibre, using ionophoresis (inject proliferate, and w invading macrophages & microglia charged substance on muscle) ,move ACh pipette across from blood, phagocytize the axonal & myelin debris muscle fibre   recycle nutrients  Focus on blue line o Cell body & nucleus of injured neuron swell  If pipette ACh directly on end-plate  large response  Several hrs later: o Even if pipette 1 mm away  no response o Axon sprouts near proximal region & begins to regenerate  Since high conc of ACh in end-plate region o Schwann cells preserve endoneural tube so axon can  Denervate  grow back thru o Amplitude of end-plate stays same, also in neighbouring  If a connection is reestablished  cell body resumes its normal regions position o Response all across muscle o Axon regenerates along the column of Schwann cells  Fibrilation:  If a connection not reestablished  cell often dies rapidly o Denervated muscle shows spontaneous, asynchronous  After axotomy: contractions o Degeneration of nerve terminal & distal segment of axon o Also in heart & skeletal muscles since also have AChRs o Macrophages & microglia invade & phagocytize the debris  Fibrilations originated in end-plate regions from changes in o Presynaptic terminals retract membrane (not ACh)  Due to retrograde signals following axotomy o Resistant to Na channels   reduce synaptic transmission onto this axon  Denervated muscle does so because of super-sensitive to ACh (1000x) o Super-sensitivity to ACh  increase in AChRs  Increases chance of having motoneuron innervate it  W more time  muscle begins to atrophy & waste away (if reinnervation doesn’t happen) o Need a lot of physical therapy to activate muscles & avoid atrophy  Area sensitive to ACh increases until almost uniform distribution of ACh across muscle surface Effects of Denervation on Postsynaptic Cells  Distribution & turnover of AChRs often studied by labeling them w radioactive α-bungarotoxin – binds to AChRs  These are new Rs, not simply Rs diffused from synaptic region o Viewed by increase in radioactivity o Can use antagonists  Apprearance of new AChRs is blocked by prot synthesis  Neurons that synapse onto damaged cell are also affected inhibitors o Ex. actinomycin  bath in it follow denervation  no  B: Put cuff around moto axon  “nerve block” - prevent act pot increase in sensitivity firing – like denervating o Muscle fibre now supersensitive o All along muscle fibre have signals at level of end-plate o Shows synaptic transmission itself is important  1 hypothesis: diffused AChRs across muscle – if true, would expect smaller response across muscle, so false  Subunit composition is different  Squiggles = nuclei, producing mRNA  What you really need is electrical activity in the motoneuron  B: Adult motoneuron synapsing on end-plate o Without it  supersensitivity in muscle o Surface texture increases surface area  Can rescue supersensitivity by stimulating axon itself  A: Fetal tissue – around time synapses forming  If stimulate muscle  Lower ACh sensitivity further from end- o Full muscle produces Rs, to promote innervate plate o Many nuclei making mRNA  C: now have expression of Rs all across muscle fibres, but most are embryonic type o Rehabituation of development  promote synapse formation o Works well in PNS but not at all in CNS  If reinnervate  stimulate muscle, revert back to adult form  D: if stimulate muscle fibre w electricity  stimulate muscle  Use 2 fluorescent-type antibodies o Red = synaptic vesicles (presynaptic region of synapse) o Green = AChRs (marker of postsynaptic region)  Clusters of bright green at pres