NSC 300 - Ch 8: Synaptic Plasticity

synaptic plasticity

change in synaptic strength due to prior activity

• can occur over short (msec) or long (years) periods of time

synaptic facilitation

a rapid increase in synaptic strength that occurs when >=2 APs invade the presynaptic terminal w/in a few milliseconds of each other

synaptic depression

a short - term decrease in synaptic strength resulting from the depletion of synaptic vesicles at active synapses

• causes NT release to declines during sustained synaptic activity

• depends on amount of NT that has been released

• lowering external [Ca2+] to reduce the # of quanta released by each presynaptic AP

what causes synaptic depression?

progressive depletion of a pool of synaptic vesicles that are available for release

• when rates of release are high, vesicles deplete rapidly & cause lots of depression

• depletion slows as the rate of release is reduced

potentiation

an activity-dependent form of short term synaptic plasticity that enhances synaptic transmission

• timescale: tens of seconds - minutes

what causes potentiation?

• caused by increase in amount of NT released in response to presynaptic APs

• results from persistent Ca actions w/in presynaptic terminals

augmentation

an activity-dependent form of short-term synaptic plasticity that enhances synaptic transmission

• timescale: few seconds

what causes augmentation?

• caused by an increase in the amount of NT released in response to presynaptic AP & results from persistent Ca signaling w/in presynaptic terminals

• could be due to actions on SNARE-regulatory protein, munc13

post-tetanic potentiation (PTP)

when potentiation greatly outlasts the tetanic stimulus that it induces

• an enhancement of synaptic transmission resulting from high-frequency trains of AP

habituation

a process that causes the animal to become less responsive to repeated occurrences of a stimulus

• reduced behavioral responsiveness to the repeated occurrence of a sensory stimulus

sensitization

a process that allows an animal to generalize an aversive response to a variety of other, non-noxious stimuli

• increased sensitivity to stimuli in area surrounding an injury

long-term potentiation (LTP)

a form of long-term synaptic plasticity that produces a persistent, activity-dependent strengthening of synaptic transmission

• occurs at 3 excitatory synapses of hippocampus

properties of LTP

• requires strong activity in both presynaptic & postsynaptic neurons

  • increase in synaptic transmission occurs only if paired activities of postsynaptic cells are tightly linked in time

  • like the strong postsynaptic depolarization occurs w/in 100 msec of transmitter release from Schaffer collaterals

• LTP is input specific

  • when LTP is induced by activation of 1 synapse, it doesn’t occur in other, inactive synapses that contact the same neuron

    • LTP is restricted to activated synapses rather than to all the synapses on a given cell

long-term depression (LTD)

a form of long-term synaptic plasticity that produces a persistent, activity-dependent weakening of synaptic

coincidence detector

a device that detects the simultaneous presence of 2 or more signals

• allows LTP to occur only when presynaptic & postsynaptic neurons are active

associativity

a mechanism that serves to link together two or more independent processes

• important LTP

mechanism of presynaptic enhancement underlying behavioral sensitization

1. serotonin released by the modulatory interneurons binds to G-protein-coupled receptors on the presynaptic terminals of the siphon sensory neurons

2. stimulates production of the 2nd messenger, cAMP

3. cAMP binds to the regulatory subunits of protein kinase A

4. liberating catalytic subunits of PKA that are then able to phosphorylate several proteins, probably including K+ channels

5. the net effect of PKA action is to reduce the probability that the K+ channels open during a presynaptic AP

   • this prolongs the presynaptic AP thereby opening more presynaptic Ca2+ channels

6. the enhanced influx of Ca2+ into the presynaptic terminals increases the amount of transmitter released onto motor neurons during a sensory neuron AP

synaptic mechanisms underlying short-term sensitization

• facilitatory interneuron releases serotonin

• serotonin binds to G-protein coupled receptor on presynaptic terminal of sensory neuron

• activates cAMP production

• increase activation of cAMP → increase sensitization b/c K+ channel

• PKA activation closes S-type K+ channels

• sensory neuron releases more transmitter

• long-term sensitization involves new gene transcription

• PKA activated MAP-kinase/CREB pathway

• CREB activates early & late genes

• leads to generation of new synaptic contacts

Aplysia learning - classical conditioning

Presynaptic: similar to sensitization

• due to Ca2+/calmodulin activates adenylyl cyclase

• pairs w/ tail shock for strong activation of adenylyl cyclase

Postsynaptic: glutamate response in motor neurons

• coincident activation of motor neuron by tail & mantle neurons activates NMDA receptors

• Ca2+ influx activates retrograde signal to presynaptic neurons

categories of memory

declarative: available to consciousness (recalling what you did)

• daily episodes

• words & their meanings

non-declarative: generally not available to consciousness (procedural & associative learning)

• motor skills

• associations

• priming cues

• puzzle-solving skills

brain areas that support declarative memory

hippocampus

• part of forebrain

• 3 layers of cells

• integrates inputs → cortical association

• parts limbic system

long-term potentiation of Schaffer collateral - CA1 synapses

key properties:

1. input specific: only co-active synapses are strengthened

2. state-dependent: presynaptic activity must be coupled w/ postsynaptic depolarization

3. associative: pairing weal stimulation w/ strong stimulation will potentiate weak synapse

NMDA receptors act as “coincidence detectors”

• detect presynaptic NT release & strong postsynaptic depolarization

  • temporal or spatial stimulation

• allow Ca2+ to enter postsynaptic cell

  • Ca2+ goes through channel into cell

• LTP has early, intermediate, & late effects

  • multiple metabolic activities occur (gene transcription: hrs → days)

AMPA receptors

• allow Na+ to flow & Ca2+ into cell

• only requiring glutamate

• only need weak stimulation

silent synapses

Presynaptic effects - early LTP

• enhanced NT release from presynaptic neurons

• may be due to a retrograde signal from the postsynaptic neuron

Postsynaptic effects - intermediate LTP

• PK’s phosphorylate AMPA receptors to increase their conductance

• new AMPA receptors added to the membrane

long-term synaptic depression in the hippocampus

• acts to weaken synaptic strengths

• found in many locations in the brain

  • heavily studied in cerebellum, hippocampus

• long term, low frequency stimulation can trigger LTD

  • triggered by Ca2+ entry

  • activated protein phosphatases

  • internalization of AMPA receptors

long term synaptic depression in the cerebellum

• synapses b/w parallel fibers & Purkinje cells (GABA containing)

• coincident activation of parallel fibers & climbing fibers

• activation of mGluRs + depolarization enhances Ca2+ release

• phosphorylation of AMPA receptors mediates endocytosis

spike-timing dependent synaptic plasticity in cultured hippocampal neurons

LTD requires postsynaptic activity prior to presynaptic activity

• weaken response

• suppressed

LTP requires presynaptic activity prior to postsynaptic activity

• strong response

• enhanced

• presynaptic then postsynaptic

Due to differences in activation of NMDA receptors