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Synaptic Transmission / Central Synapses I
Tom O’DellDepartment of Physiology
[email protected] (NPI), x64654
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• Basic features of synaptic transmission in the CNS
• Fast excitatory synaptic transmission: Acetylcholine
• Fast excitatory synaptic transmission: Glutamate
Lecture Topics
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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
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Synaptic Transmission at Many CNS SynapsesIs Weak and Unreliable
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V1
V2
V3
Synapse
Synaptic Potentials Propagate Passively
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Passive Propagation Means Location is Important
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Temporal and Spatial Summation
Temporal Summation
Spatial Summation
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Nicotine is Addictive
Le Foll and Goldberg 2006
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H3 nicotine I125 BTX
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Neuronal Nicotinic Acetylcholine Receptors:8 ’s and 3 ’s
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Neuronal Nicotinic Ach Receptors
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Time (min.)
-10 0 10 20 30
EP
SP
(%
Bas
elin
e)
75
100
125
150
175
200 Nic
Nicotine enhances excitatory synaptic transmission
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Fast Excitatory Synaptic Transmission in the CNS: Glutamate
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Glutamate Receptors
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Stimulate
Record
Excitatory Postsynaptic Potentials are due to AMPA Receptor Activation
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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
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Calderone A et al. J. Neurosci. 23: 2003
Delayed Cell Death Induced by Transient Global Ischemia
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GluR1 GluR2
Control 24 Hrs Post-ischemia
GluR1 GluR2
Control 24 Hrs Post-ischemia
AMPA AMPA
Transient Ischemia Down-Regulates GluR2 Expression
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Mg2+ Block of NMDA Receptor Ion Channel MakesNMDA Receptors Voltage-Dependent
PCa2+/PNa = 10
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NMDA Receptors Require Glycine as a Co-agonist
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Kainate Receptors have Unique Roles in ExcitatorySynaptic Transmission
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Kainate Receptors have Unique Roles in ExcitatorySynaptic Transmission
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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