1. Announcements Mid term room assignments posted to webpage A – HoS361 (Pavilion) Hoang – LischkaS309 Lishingham - NguiS143 Nguyen – SeguinS128 Sek – ZiaH305 Lecture 02S319 Lecture 01

2. A. Excitor B. Inhibitor Record voltage

3. Simple case: Vm Threshold Depolarizing  excitatory EPSP hyperpolarizing  inhibitory IPSP Vm Threshold B A A+B=smaller

4. How to get hyperpolarizing potential? Neurotransmitter receptor is permeable to an ion whose E ion is more negative than resting membrane potential usually Cl- or K+

5. + + -80 mV +60 mV 0 mV Hyperpolarizing Synaptic Potential K+

6. More complex case: Vm Depolarizing  excitatory Depolarizing  Threshold B A Vm A+B=smaller inhibitory Why???

7. Reversal Potential Membrane potential at which there is no net synaptic current

8. eg. Frog NMJ Control resting membrane potential Current source stimulus -100 -50 0 +25 Measuring Reversal Potential Reversal potential Record membrane potential Stimulate nerve

9. Many neurotransmitter receptors are permeable to more than one ion –Non-selective The reversal potential depends on the equilibrium potential and permeability of each ion –It will usually be between the equilibrium potential of the permeable ions

10. eg. Acetylcholine channel Permeable to both K+ and Na+ For Frog muscle: E K = -90 mV E Na = +60 mV

11. Vm=E rev E rev >Vm>E K Vm  E K Na+ Vm  E Na K+ E K = -90 mV Neurotransmitter receptor -90 E Na = +60 mV -50 0 +25 Reversal potential

12. How can depolarizing potential be inhibitory? Excitatory synapses have a reversal potential more positive than threshold Inhibitory synapses have a reversal potential more negative than threshold

13. How can depolarizing potential be inhibitory? Vm Threshold B A E rev Example: Cl - permeable receptor in a cell whose V thresh >E Cl - > Vm

14. Inhibition Channels of inhibitory synapses ‘short- circuit’ excitatory synapses Because neurotransmitter channels will drive the membrane potential toward their reversal potential

15. Neurotransmitters and receptors Synaptic Integration

16. Types of Receptors 1.Ligand-gated ion channels Neurotransmitter binding to receptor opens an ion channel Directly changes the membrane potential of the postsynaptic cell Also known as ‘fast’ synaptic transmission 2.G-Protein Coupled Receptors Transmitter binds to receptor which activates intracellular molecules Can directly or indirectly change the membrane potential Also known as ‘slow’ synaptic transmission

17. Neurotransmitter Receptors Ligand-gated ion channels Acetylcholine (Nicotinic) Excitatory Glutamate (AMPA, NMDA) Excitatory Serotonin (5-HT 3 ) Excitatory GABA A Inhibitory GlycineInhibitory

18. Neurotransmitter Receptors G-Protein coupled receptors Acetylcholine (muscarinic) Usually excitatory Glutamate (metabotropic) Variable effects Serotonin (5-HT1-7) Variable effects GABA B inhibitory Same neurotransmitter, different receptors

19.    Activate intracellular molecules Open or close ion channel direct effect G-protein coupled receptor Regulate other cellular functions eg gene expression GTP GDP receptor G-proteins indirect effect

20. What happens to neurotransmitter after it is secreted? Acetylcholine –Broken down by Acetylcholinesterase into Choline and Acetate –Choline transported back into nerve terminal and resynthesized into Acetylcholine Glutamate –Transported into glia or the nerve terminal and converted to glutamine

21. Serotonin –A neurotransmitter used in the emotional centres of the brain –Prozac is a drug that inhibits the reuptake of serotonin –Therefore, Prozac makes serotonin remain in synaptic cleft longer

22. Synaptic Integration The sum of all excitatory and inhibitory inputs to a cell. 1.Spatial Summation 2.Temporal Summation

23. Spatial Summation The addition of several inputs onto one cell A B B A A+B B A

24. Temporal Summation A Stim once Stim twice

25. Synaptic Integration Soma and dendrites Synaptic inputs Axon Hillock Passive current flow Above threshold? Yes No Action Potential Passive Current Decays to zero Summation Conducts down axon

26. Summary Excitation and inhibition in relation to the reversal potential Fate of neurotransmitters after release Types of transmitters and their receptors Synaptic integration leading to action potentials