synaptic plasticity

how does the brain store info?

∆ing the amplitude/duration of synaptic events

potentiation

An increase in synaptic strength, making it easier for a neuron to fire in response to a given stimulus.

depression

A decrease in synaptic strength, making it harder for a neuron to fire in response to a stimulus.

synaptic strength can change by increasing/decreasing (3):

1. number of release sites

2. probability of neurotrans release

3. # or properties of postsynaptic ligand-gated receptors

n =

• # of synapses

p =

probability of release

q =

• quantal size

• amplitude of the postsynaptic response to the glutamate from one vesicle

short-term facilitation

1. Ca2+ enters nerve terminal after 1st presynaptic AP

   1. causes small amount of neurotrans release

2. 2nd presynaptic AP → Ca2+ accumulates causing greater neurotrans release

post-tetanic potentiation

• residual Ca2+ in presynaptic terminal caused by high frequency firing leads to short-term enhancement of synaptic transmission

• caused by accumulation of Ca2+

short-term depression

• occurs where release probability is initially high

• 1st event: Ca2+ causes large amount of transmitter release

• 2nd event: not enough vesicles readily available for for an equally large transmitter release

  • synaptic events getting smaller

  • fewer release of vesicles in the readily releasable pool during refractory period

facilitation

• occurs at synapses where release probability is low

  • not v. high chance of releasing

• Ca2+ facilitates vesicle fusion

• as time increases facilitation becomes less apparent bc no more Ca2+ accumulation

readily-releasable pool of vesicles

• 5-8 vesicles in the active zone

• ready to be released one at a time

  • special synapses may release 2-3 at a time

reserve pool of vesicles

• 17-20 vesicles

• spatially behind → move into place as vesicles are fusing

resting pool of vesicles

• 180 vesicles

• helps replenish reserve pools

________ and ________ are important variables for short-term plasticity

• # of vesicles in the readily releasable pool

• how quickly the pool can be refilled

how to ∆ synaptic strength

• postsynaptic receptor could become desensitized

• OR could be phosphorylated → ∆ing their open time/conductance

paired pulse ratio

• second evoked current over the first

• B/A

increase in presynaptic efficacy effect on paired pulse ratio

• decrease in paired pulse ratio (B/A < 1)

• increase in miniature (EPSC) frequency

decrease in presynaptic efficacy effect on paired pulse ratio

• increase in paired pulse ratio (B/A > 1)

• decrease in miniature (EPSC) frequency

increase in postsynaptic efficacy effect on paired pulse ratio

• no ∆ in paired pulse ratio (B/A) or miniature frequency

• amplitude increase in all currents

  • current gets bigger but ratio doesn’t change (they both get bigger)

decrease in postsynaptic efficacy effect on paired pulse ratio

• no ∆ in paired pulse ratio (B/A) or miniature frequency

• amplitude decrease in all currents

  • both get smaller

  • could have changed quantal size = # of reeptors

phosphorylation of AMPA receptors

This suggests that phosphorylation of GluR4 enhances the synaptic response.

what happens to AMPA receptors when a cAMP blocker is added

inhibition of PKA prevents the effects of phosphorylation on AMPARs.

2-AG (2-arachidonoylglycerol)

• endocannabinoid

• acts as retrograde messenger in brain

Endocannabinoids

• produced by postsynaptic neurons and act on presynaptic receptors to modulate neurotransmitter release

in GABAergic synapse, CB1 receptors (cannabinoid receptors) are activated by

• 2-AG, leading to the short-term depression (DSI) of synaptic transmission through a cascade involving G_i/o proteins.

in glutamatergic synapse, CB1 receptors (cannabinoid receptors) are activated by

2-AG and leads to short-term depression (DSE).

Significance of DSI/DSE

• important for modulating synaptic activity and maintaining balance between excitation and inhibition in neural circuits.

• help to prevent excessive excitation or inhibition, ensuring proper neuronal network functioning.

what happens to IPSC current when a CB1 agonist is added

• activation of CB1

• decrease in IPSC amplitude following the application of WIN

• significant increase in the paired-pulse ratio with WIN (p < 0.05),

  • indicating that the CB1 receptor activation by WIN affects synaptic function, likely by reducing neurotransmitter release or affecting synaptic plasticity.

what happens to IPSC current when a CB1 antagonist is added

• block CB1 receptor signalling

• a return to baseline when SR14 is applied, indicating a reversal of the effects of WIN by the antagonist

what does a high paired pulse ratio suggest

• A higher ratio typically suggests reduced synaptic depression or altered neurotransmitter release.

long-term potentiation (LTP)

long-lasting enhancement in signal transmission between two neurons that results from stimulating them synchronously

Long-term depression (LTD)

long-lasting attenuation in signal transmission between two neurons.

NMDA receptor

• permeable to Ca2+ in addition to K+ and Na+

• requires d-serine/glycine as a cofactor

• voltage dependent (Mg+ block)

• opens + closes slowly

where to ∆ # of AMPA receptors for long-term potentiation/depression

in the post synapse

negative membrane potentials (around -100 mV), there is little to no current passing through the NMDA receptor channel because

magnesium (Mg²⁺) ions block the channel at resting membrane potential (typically negative).

what happens to NMDA receptor when membrane potential becomes more positive (towards 0 mV and beyond)

magnesium block is relieved due to the depolarization of the membrane, and current starts to flow