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Synaptic Transmission / Central Synapses I

Synaptic Transmission / Central Synapses I. Tom O’Dell Department of Physiology. todell@mednet.ucla.edu C8-161 (NPI), x64654. Lecture Topics. Basic features of synaptic transmission in the CNS Fast excitatory synaptic transmission: Acetylcholine

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Synaptic Transmission / Central Synapses I

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

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

  3. NMJ Vs. Central Synapses NMJ CNS 1. One-to-one Input from 100’s of presynaptic 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

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

  5. Synapse V1 V2 V3 Synaptic Potentials Propagate Passively

  6. Passive Propagation Means Location is Important

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

  8. Nicotine is Addictive Le Foll and Goldberg 2006

  9. H3 nicotine I125 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. Excitatory Postsynaptic Potentials are due to AMPA Receptor Activation Stimulate Record

  16. GluR2 Subunit lacking Receptors GluR2 Subunit Containing Receptors PCa2+/PNa = 1 – 3 PCa2+/PNa = 0.01 – 0.05 GluR2 subunits Regulate the Calcium Permeability of AMPA Receptors

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

  18. Transient Ischemia Down-Regulates GluR2 Expression Control 24 Hrs Post-ischemia GluR1 GluR2 GluR1 GluR2 Control 24 Hrs Post-ischemia AMPA AMPA

  19. Mg2+ Block of NMDA Receptor Ion Channel Makes NMDA Receptors Voltage-Dependent PCa2+/PNa = 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 • 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

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