1. Synaptic Transmission / Central Synapses I Tom O’Dell Department of Physiology todell@mednet.ucla.edu C8-161 (NPI), x64654

2. Basic features of synaptic transmission in the CNS Fast excitatory synaptic transmission: Acetylcholine Fast excitatory synaptic transmission: Glutamate Lecture Topics

3. NMJ Vs. Central Synapses NMJCNS 1. One-to-oneInput from 100’s of presynaptic cells 2. Inputs are only Inputs can be excitatory, inhibitory, excitatoryand modulatory 3. One neurotransmitterMany different transmitters (Ach)(and receptors, even for same NT) 4. Extremely ReliableSome have high safety factors (high safety factor)but many can be very unreliable

4. Synaptic Transmission at Many CNS Synapses Is Weak and Unreliable

5. V1 V2 V3 Synapse Synaptic Potentials Propagate Passively

6. Passive Propagation Means Location is Important

7. Temporal and Spatial Summation  Temporal Summation  Spatial Summation

8. Nicotine is Addictive Le Foll and Goldberg 2006

9. H 3 nicotineI 125 BTX

10. Neuronal Nicotinic Acetylcholine Receptors: 8  ’s and 3  ’s

11. Neuronal Nicotinic Ach Receptors

12. Nicotine enhances excitatory synaptic transmission

13. Fast Excitatory Synaptic Transmission in the CNS: Glutamate

14. Glutamate Receptors

15. Stimulate Record Excitatory Postsynaptic Potentials are due to AMPA Receptor Activation

16. GluR2 subunits Regulate the Calcium Permeability of AMPA Receptors P Ca 2+ /P Na = 1 – 3P Ca 2+ /P Na = 0.01 – 0.05 GluR2 Subunit lacking ReceptorsGluR2 Subunit Containing Receptors

17. Calderone A et al. J. Neurosci. 23: 2003 Delayed Cell Death Induced by Transient Global Ischemia

18. GluR1GluR2 Control24 Hrs Post-ischemia GluR1GluR2 Control24 Hrs Post-ischemia AMPA Transient Ischemia Down-Regulates GluR2 Expression

19. Mg 2+ Block of NMDA Receptor Ion Channel Makes NMDA Receptors Voltage-Dependent P Ca2+ /P Na = 10

20. NMDA Receptors Require Glycine as a Co-agonist

21. Kainate Receptors have Unique Roles in Excitatory Synaptic Transmission

22. Kainate Receptors have Unique Roles in Excitatory Synaptic Transmission

23. Glutamate Receptor Summary AMPA Receptors: Responsible for transmission at most excitatory synapses Ca 2+ impermeable channel due to presence of GluR2 subunits KA Receptors: Slow postsynaptic potentials Bi-directional effects on presynaptic transmitter release NMDA Receptors: Highly Ca 2+ permeable channel Coincidence detector - needs depolarization and glutamate for activation