1. LECTURE 8: SYNAPTIC TRANSMISSION OVERVIEW AND NMJ REQUIRED READING: Kandel text, Chapters 10,11 In humans, 10 11 neurons, each receiving average of 100-1000 synaptic inputs = 10 14 synapses !!! Multiple synapses allows a neuron to integrate information from many sources. Purkinje cells are the output cells of cerebellum, each receiving 10 5 inputs, enabling the cerebellum to monitor complex body movement and provide continual corrective signals (a corrective guidance system) Synapses undergo short-term and long-term functional adaptation. Adaptation is synapse-specific, not affecting other synapses on same cell. Short-term adaptation allows an organism to ignore certain repetitive or prolonged sensory inputs. Long-term adaptation is a cellular mechanism of learning and memory.

2. ELECTRICAL VS. CHEMICAL SYNAPSES FIGURE 10-1 TABLE 10-1

3. NEAR-INSTANTANEOUS TRANSMISSION ACROSS ELECTRICAL SYNAPSES FIGURE 10-3 Synaptic transmission is graded, occuring even in the absence of action potential Transmission can be BI-DIRECTIONAL

4. ELECTRICAL SYNAPSES ARE COMPOSED OF GAP-JUNCTION CHANNELS

5. ELECTRICAL SYNAPSES ALLOW SYNCHRONOUS FIRING OF CONNECTED CELLS

6. STEPS OF TRANSMISSION AT CHEMICAL SYNAPSES Chemical synaptic transmission has a 0.3 - 5 msec delay, depending upon type of post-synaptic receptor Chemical synaptic transmission can depolarize or inhibit depolarization, depending upon type of post-synaptic receptor Sub-threshold presynaptic depolarizations are not transmitted

7. DIRECT VS. INDIRECT GATING OF TRANSMISSION AT CHEMICAL SYNAPSES

8. DIRECTLY GATED MONOSYNAPTIC TRANSMISSION AT THE NEUROMUSCULAR JUNCTION Large size of vertebrate neuromuscular junction has facilitated electrophysiological and morphological analysis of this synapse Each muscle fiber receives input from a single motor neuron axon Synaptic transmission employs a single neurotransmitter, acetylcholine (Ach) and a single species of directly- gated neurotransmitter receptor (nicotinic AChR)

9. THE EXCITATORY POST-SYNAPTIC POTENTIAL When recording Vm near endplate, stimulation of motor axon generates complex depolarization in muscle fiber, consisting of an excitatory postsynaptic potential (EPSP) and a following action potential (AP). Partial inhibition of AChRs With curare reduces EPSP Below firing threshold For AP.

10. EPSP CURRENT APPEARS RAPIDLY AND DECAYS MORE SLOWLY

11. EPSP CURRENT OBEYS OHM’S LAW I EPSP = g EPSP x (V M - E EPSP )

12. SMOOTH EPSP CURRENT IS SUM OF CURRENTS FROM OPEN ON/OFF CHANNELS SINGLE-CHANNEL PATCH VOLTAGE CLAMP RECORDING OF ACETYLCHOLINE-INDUCED CURRENT REVERSAL POTENTIAL OF SINGLE CHANNEL SAME AS FOR OVERALL EPSP

13. STEPS OF TRANSMISSION AT NEUROMUSCULAR JUNCTION

14. MODEL OF NICOTINIC ACETYLCHOLINE RECEPTOR

15. ACH-GATED CURRENT AND PASSIVE MEMBRANE PROPERTIES DETERMINE DYNAMICS OF THE EPSP

16. NEXT LECTURE: Synaptic Integration READING: KANDEL text, Chapter 12