Synaptic transmission

1) Communication within the nervous system

2) A site of plasticity for learning and memory

3) A site of action for disease,

psychoactive drugs

Synaptic Transmission and its Modulation!

Whimpy axon!

Synaptic input

“Minis”

Quantal nature of transmitter release

Record spontaneous transmitter release

Spontaneous “mini” synaptic potentials

Quantal hypothesis of

transmitter release

Post synaptic depolarization

results from the coordinated release of transmitter packets

(quanta) from the vesicles as the AP enters the terminal

Reduce [Ca]o

Record evoked transmitter release

Normally around 300 quanta at NMJ/AP

(could be only a few at central synapses)

Spontaneous “mini” and evoked potentials- quantal steps

Quantal content: m = mean EPP/mean MEPP

Physical evidence for vesicle fusion for transmitter release

4-AP broadens presynaptic AP

Fusion of vesicles

to membrane

Ca++ channels

Steps in transmitter

release

What is the direct cause of

transmitter release?

Squid giant synapse as a

model system

EPSP

giant axon

~1 mm

Presynaptic axon

George Augustine, Marine Biological Laboratory, 2008

Importance of calcium for

transmitter release

Block transmitter release with presynaptic Ca buffer

Presynaptic Ca injection causes

transmitter release and Ca indicator dye shows presynaptic Ca entry

Any depolarization will cause transmitter release, even high Kout-

Triggers opening of voltage-gated Ca channels

What is the role of the AP in

transmitter release?

provides trigger and timing

for calcium entry

Steps in transmitter

release

What is the cause of

synaptic delay?

EPSP

Synaptic delay due to Ca entry at end of AP

ICa

EPSC

200 microS!

Plasticity of synaptic transmission

Intrinsic Synaptic Plasticity (short term)

Change in synaptic strength due to activity of synapses Important for:

coincidence detection gain control

oscillatory networks (phase onset and offset, cycle period)

Habituation, sound localization Learning and Memory

Extrinsic Synaptic Plasticity

Change in synaptic strength due to neuromodulatory substances

Important for: Network reconfiguration

Plasticity of synaptic transmission

Experimental protocol

Intrinsic Synaptic Plasticity- transforms time interval into voltage amplitude

Facilitation, Post-tetanic potentiation, Depression

Intrinsic synaptic modulation:

Facilitation

Facilitation:!! a) MEPP sizes do not change.!! b) MEPP frequency increases.!! Quanta content (m = PSP/mini) is increased!Thus, it is a presynaptic effect.!

Intrinsic synaptic modulation:

Post-tetanic potentiation

Intrinsic synaptic modulation:

Depression

Intrinsic synaptic modulation in vertebrate brains: Depends on the synapse

Dietmann et al 2000

Depression

Facilitation

Mixed