1. Neurotransmitters A. Criteria 1. must mimic presynaptic effects if administered exogenously 2. must be released during activity of presynaptic neuron 3. action must be blocked by same agents that block natural transmission

2. Neurotransmitters B. Activity 1. fast-acting (direct) - ionotropic - receptor coupled directly to ion channel

3. Neurotransmitters B. Activity 2. slow (indirect) - metabotropic - receptor coupled to membrane receptor - activation of second messenger pathways

4. Neurotransmitters B. Activity 2. slow (indirect) - metabotropic - or modulates opening of channels in response to voltage changes (neuromodulation)

5. Neurotransmitters C. Classification 1. small molecules a. acetylcholine (ACh) b. biogenic amines c. amino acids

6. Neurotransmitters C. Classification 2. neuropeptides (from all areas of nervous system) a. also from hypothalamus, pituitary, and other organs b. are often neurosecretory hormones c. also endorphins and enkephalins - bind to same receptors as opiates - endogenous opioids

7. Neurotransmitters C. Classification 3. most are highly conserved 4. fast-direct transmitters - only one type synthesized by individual neurons a. ACh - cholinergic neurons (i. e., neuromuscular junction) - curare is antagonist

8. Neurotransmitters C. Classification - acetylcholinesterase breaks ACh down to acetate and choline - choline recycled in presynaptic neuron - blocked by some toxins (Sarin, tetanus)

9. Neurotransmitters C. Classification 4. fast-direct transmitters b. glutamate - excitatory in vertebrate CNS

10. NMDA receptors are ionotropic glutamate receptors these modulate Ca ++ channels

11. Neurotransmitters C. Classification 4. fast-direct transmitters c. GABA-A (  -aminobutyric acid) - inhibitory at ”glutamate” synapses

12. d. glycine - inhibitory - can modulate glutamate

13. d. glycine - inhibitory - some have chloride ionophore function

14. Biogenic Amines/Monoamines A. Serotonin - derived from tryptophan Selective Serotonin Reuptake Inhibitors - slow, indirect transmission - metabotropic

15. Biogenic Amines/Monoamines B. Catecholamines - derived from tyrosine - adrenergic neurons 1. epinephrine/adrenaline (hormone and neurotransmitter)

16. Biogenic Amines/Monoamines B. Catecholamines - derived from tyrosine 2. norepinephrine/noradrenaline (hormone and neurotransmitter) - many psychoactive drugs mimic NE - amphetamines - cocaine (prevents inactivation of NE) 3. dopamine

17. Biogenic Amines/Monoamines C. Release and uptake 1. similar release to ACh 2. rapid inhibition following release a. reuptake to presynaptic neurons b. monoamine oxidase in presynaptic neuron

18. Regulation Desensitization/Down-regulation - initially a decrease in affinity - long-term becomes loss of receptors

19. Regulation Super-sensitivity/Up-regulation - seen in synapses that are rarely used

20. Regulation Long-term potentiation - an increase in the strength of synaptic transmission with repetitive use that lasts for more than a few minutes - in hippocampus can be triggered in less than 1 second of intense synaptic activity

21. Regulation Long-term potentiation Model: 1. afferent stimulus causes release of glutamate 2. glutamate binds to NMDA and non-NMDA receptors on postsynaptic membrane (Na + influx) 3. EPSP causes removal of Mg ++ which normally hinders Na + and Ca ++ influx 4. Ca++ influx leads to activation of postsynaptic protein kinase, which induces an LTP.