1. Sci2 Lect 5 Synaptic Transmission ©Dr Bill Phillips 2002, Dept of Physiology Fast Excitatory Postsynaptic Potentials Ligand gated ion channels Presynaptic neurotransmitter release Fast inhibitory synapses Local circuit currents- synaptic integration Slow synaptic transmission

2. Fast and slow chemical synaptic transmission FAST SYNAPTIC TRANSMISSION Transmitter binds to and opens ligand- gated ion channels Response takes no more than a few milliseconds SLOW SYNAPTIC TRANSMISSION Transmitter binds receptor that activates second messenger signalling in postsynaptic cell Response takes seconds or minutes

3. Fast Excitatory Postsynaptic Potentials Excitatory synapse Excitatory synapse

4. Steps in fast chemical transmission: Nerve AP depolarises nerve terminal Voltage-gated Ca 2+ channels in terminal open leading to  [Ca 2+ ] i  [Ca 2+ ] i triggers release of transmitter into the synaptic cleft Transmitter activates postsynaptic ligand-gated ion channels, opening them Altered membrane current depolarises or hyperpolarises postsynaptic cell

5. Ligand-gated cation channels like the nicotinic acetylcholine receptor (AChR) are permeable to both Na + and K +. Why does opening of these cation channels result in depolarisation of the postsynaptic membrane? ?

6. Stimulate

7. Miniature (quantal) responses Electrical recordings from postsynaptic cells reveal Excitatory PostSynaptic Potentials (EPSPs) when follow transmitter release from presynaptic nerve terminals EPSPs seem to be made up of the Summation of small (~0.5mV) Miniature EPSPs sometimes referred to as quanta

8. Vesicle/quanta hypothesis Most neuroscientist think transmitter chemicals are released in discrete packets or quanta The vesicle hypothesis says that these quanta are contained in synaptic vesicles that are released by a form of exocytosis The ~uniform size of the synaptic vesicles may explain the fairly uniform quantal amplitude of the postsynaptic response.

9. Presynaptic neurotransmitter release: eg glutamate from excitatory nerve terminals Glut Glutamate receptors

10. Role of Ca 2+ in transmitter release Amplitude of EPSP depends on [Ca 2+ ] o [Ca 2+ ] o normally ~1mM if lowered to 0.5mM, number of quanta released drops greatly, suggesting that the mechanism of neurotransmitter release is dependent upon the concentration of Ca 2+ inside the terminal following the action potential. SELF TEST- WHY?

11. Fast inhibitory synapses* Major inhibitory neurotransmitters: Gamma amino butyric acid (GABA), glycine Ligand-gated Cl - channels (eg GABA A receptor) *Often found on neuron soma And proximal dendrites

12. How do fast inhibitory synapses work? GABA A receptors and glycine receptors are Ligand-gated channels selective for Cl - [Cl - ] o >>[Cl - ] i concentration gradient into cell Opening of these channels   inward current of Cl - equivalent to an  outward current of +ve ions Hyperpolarise soma, or short-circuit depolarising local circuit currents coming from excitatory synapses

13. Local circuit currents- synaptic integration

14. Summation of postsynaptic currents Excitatory Postsynaptic Currents (EPSCs) spread through dendrites to cell body (soma) Local circuit currents diminish with distance due to resistance of cytoplasm and leakage channels in dendrite membrane EPSCs from many synapses on different branches of the dendritic ‘tree’ sum together at the axon hillock where a ‘decision’ is made whether an action potential/s is triggered

15. Synaptic integration Plasma membrane stores electrical charge this means brief opening of channels results in much longer slower changes in V m (capacitance properties) Summation of EPSCs occuring within a few milliseconds of each other sum to raise V m When Inhibitory Postsynaptic Currents (IPSCs) occur at the same time as EPSCs they help to lower the V m and reduce the chance that action potential/s will be triggered at the axon hillock

16. Fast and slow chemical synaptic transmission FAST SYNAPTIC TRANSMISSION Transmitter binds to and opens ligand- gated ion channels Response takes no more than a few milliseconds SLOW SYNAPTIC TRANSMISSION Transmitter binds receptor that activates second messenger signalling in postsynaptic cell Response takes seconds or minutes

17. Slow synaptic transmission Produce delayed changes in postsynaptic current or other changes in postsynaptic cell Seconds or minutes to take effect Many types: can involve familiar transmitters (eg glutamate, GABA) or different ones (eg dopamine, noradrenaline) Different types of receptors- often G-protein- coupled receptors that work through second messenger systems

18. Slow synaptic transmission: Effects Depending on transmitter, receptor and second messenger system involved may: Depolarise postsynaptic cell Hyperpolarise Reduce or increase membrane resistance Modify gene expression Modify transmitter release