BIOL 376 - Unit 4: Synaptic Pruning, Plasticity

when does synaptic pruning and apoptosis start?

4 months after birth

( )% of neurons removed during programmed cell death

50

conditions to induce programmed cell death in PNS

TrkA and TrkC expression with absence of NGF and NT3

conditions to induce programmed cell death in CNS

not dependent on neurotrophic factors

pruning

weakening OR complete removal of synaptic connections

3 main mechanisms of pruning

axon retraction, axon degeneration, axon shedding

axon degeneration

axons degenerate from proximal to distal end

Wallerian degeneration

distal axon separates from soma, catastrophic fragmentation

Wallerian degeneration steps 1 and 2

injury, swollen beaded axon

Wallerian degeneration steps 3 and 4

myelin degeneration, axon cytoskeleton breakdown

Wallerian degeneration step 5

glial cells clear debris, promote new axon formation

in development, injury is replaced by cellular signals to induce…

hormonal degeneration, genetic switches

axon retraction

nerve shortens from distal to proximal end

what influences formation of a retraction bulb? (axon retraction)

neurotrophic factors, cell-substrate adhesion, cell activity

what are used to induce axon retraction in HIPPOCAMPAL PROJECTIONS?

semaphorins, neuropilins, plexins

what are used to induce axon retraction in the RETINA?

ephrin, Eph

axon shedding

distal to proximal breakdown of axon branches

synaptic competition

competing synapses occupy similar locations, covered by perisynaptic Schwann cells

losing neuron…

retreats from synapse

axosome shedding (of synapse and axon)

shedding of axoplasm-containing axosomes

perisynaptic Schwann cell

engulfs axosomes and breaks them down

synaptic rearrangement

occurs due to neural activity and synaptic transmission

synaptic rearrangement triggers…

intracellular Ca2+, influencing cytoskeletal organization and gene expression

critical period

crucial temporal window for synaptic development and pruning

NOTE: Know and be able to describe Hubel and Wiesel’s feline experiment

Hebb’s postulate

neurons that fire together, wire together

if signals from one set of neurons is closely correlated with the output of other, these synapses will be ( ), others are ( )

strengthened, removed

Hebb’s postulate, second part

neurons that fire out of sync, lose their link

synaptic plasticity

ability of synapses to strengthen or weaken over time in response to change in neuronal activity

short-term plasticity

lasts for a few minutes or less

short-term plasticity mechanisms

facilitation, depression, augmentation, post-tetanic potentiation

facilitation (short-term)

caused by prolonged elevation of presynaptic Ca2+ levels following synaptic activity

depression (short-term)

dependent on progressive depletion of synaptic vesicles in presynaptic terminal

augmentation and post-tetanic potentiation

increases amount of transmitter released from presynaptic terminals

augmentation speed

fast, over a few seconds

augmentation process

Ca2+ enhances action of munc-13 to prime readily-releasable vesicles

post-tetanic potentiation speed

10 seconds to minutes

post-tetanic potentiation process

Ca2+ enhances actions of presynaptic protein kinases to phosphorylate substrates, regulating transmitter release

long-term plasticity most studied in the…

hippocampus

hippocampus functions

formation and retrieval of memories

damage to hippocampus…

results in inability to form certain types of memories

neuronal layers involved in hippocampal long-term potentiation

CA1, CA3

presynaptic pyramidal cells in ( ) region sends synapse to pyramidal cells in ( ) region via ( )

CA3, CA1, Schaffer collaterals

NOTE: Know Lomo and Bliss experiment with rodent hippocampus

long-term potentiation lasts for…

greater than a year

long-term potentiation also found in…

cerebral cortex, amygdala, cerebellum

long-term potentiation is a Hebbian synapse, this means…

stimulus to Schaffer collaterals must be paired with strong depolarization of postsynaptic CA1 cell to undergo long-term potentiation

strong postsynaptic depolarization must occur within ( ) of presynaptic transmitter release for long-term potentiation to occur

100 ms

long-term potentiation, glutamate release, binds to both…

NMDA and AMPA receptors

at normal postsynaptic potential, ( ) receptor pore is blocked by ( ), thus excitatory postsynaptic potential mediated by ( ) signal associated with ( ) receptor (LTP step 1)

NMDA, Mg2+, Na+, AMPA

Mg2+ block on NMDA only opens upon… (LTP step 2)

summation of EPSPs resulting in prolonged depolarization

postsynaptic depolarization removes ( ) from NMDA pore, allowing ( ) to flow through the NMDA receptor (LTP step 3)

Mg2+, Ca2+

long-term potentiation is triggered by… (LTP step 4)

increase in Ca2+ in dendritic spines of postsynaptic cell

NMDA receptor only opens to induce long-term potentiation when there is ( ) bound to the NMDA receptor along with the ( ) block

glutamate, Mg2+

long-term potentiation must be…

specific and associative

Ca2+ entering through NMDA receptors activates ( ) and ( )

CaMKII, PKC

mutation of CaMKII protein at Schaffer collateral synapses…

prevents long-term potentiation

CaMKII can ( ) and prolongs ( ) of long-term potentiation

autophosphorylate, duration

long-term potentiation is maintained from ( ), leads to increase in membrane expression of postsynaptic ( ) receptors

kinase phosphorylation, AMPA

long-term potentiation duration

minutes to hours

long-term sustained long-term potentiation last for more than ( ), involves changes in ( ) and ( ) expression

2 hours, gene, protein

late-phase long term potentiation is due to ( ) activation, leading to phosphorylation and activation of ( ), turning on gene transcription

PKA, CREB

long-term depression

selective weakening of synapses

low stimulation of Schaffer collateral-CA1 path for 10-15 minutes induces…

long-lasting depression of synaptic transmission

long-term depression is also activated by…

Ca2+ entry into postsynaptic NMDA receptor

long-term potentiation activates ( ), long-term depression activates ( )

protein kinases, Ca2+-dependent phosphatases

long-term depression associated with…

internalization of AMPA receptors

internalization of AMPA receptors is via…

clathrin-dependent endocytosis

long-term potentiation and long-term depression both reversibly…

affect synaptic efficacy