synaptic transmission / central synapses i

Synaptic Transmission / Central Synapses I

Tom O’DellDepartment of Physiology

todell@mednet.ucla.eduC8-161 (NPI), x64654

• Basic features of synaptic transmission in the CNS

• Fast excitatory synaptic transmission: Acetylcholine

• Fast excitatory synaptic transmission: Glutamate

Lecture Topics

NMJ Vs. Central Synapses

NMJ CNS

1. One-to-one Input from 100’s ofpresynaptic cells

2. Inputs are only Inputs can be excitatory, inhibitory, excitatory and modulatory

3. One neurotransmitter Many different transmitters (Ach) (and receptors, even for same NT)

4. Extremely Reliable Some have high safety factors (high safety factor) but many can be very unreliable

Synaptic Transmission at Many CNS SynapsesIs Weak and Unreliable

V1

V2

V3

Synapse

Synaptic Potentials Propagate Passively

Passive Propagation Means Location is Important

Temporal and Spatial Summation

Temporal Summation

Spatial Summation

Nicotine is Addictive

Le Foll and Goldberg 2006

H3 nicotine I125 BTX

Neuronal Nicotinic Acetylcholine Receptors:8 ’s and 3 ’s

Neuronal Nicotinic Ach Receptors

Time (min.)

-10 0 10 20 30

EP

SP

(%

Bas

elin

e)

75

100

125

150

175

200 Nic

Nicotine enhances excitatory synaptic transmission

Fast Excitatory Synaptic Transmission in the CNS: Glutamate

Glutamate Receptors

Stimulate

Record

Excitatory Postsynaptic Potentials are due to AMPA Receptor Activation

GluR2 subunits Regulate the CalciumPermeability of AMPA Receptors

PCa2+/PNa = 1 – 3 PCa2+/PNa = 0.01 – 0.05

GluR2 Subunit lacking Receptors GluR2 Subunit Containing Receptors

Calderone A et al. J. Neurosci. 23: 2003

Delayed Cell Death Induced by Transient Global Ischemia

GluR1 GluR2

Control 24 Hrs Post-ischemia

GluR1 GluR2

Control 24 Hrs Post-ischemia

AMPA AMPA

Transient Ischemia Down-Regulates GluR2 Expression

Mg2+ Block of NMDA Receptor Ion Channel MakesNMDA Receptors Voltage-Dependent

PCa2+/PNa = 10

NMDA Receptors Require Glycine as a Co-agonist

Kainate Receptors have Unique Roles in ExcitatorySynaptic Transmission

Kainate Receptors have Unique Roles in ExcitatorySynaptic Transmission

Glutamate Receptor Summary

AMPA Receptors:

• Responsible for transmission at most excitatory synapses

• Ca2+ impermeable channel due to presence of GluR2 subunits

KA Receptors:

• Slow postsynaptic potentials

• Bi-directional effects on presynaptic transmitter release

NMDA Receptors:

• Highly Ca2+ permeable channel

• Coincidence detector - needs depolarization and glutamate for activation