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Psych 181: Dr. Anagnostaras

Psych 181: Dr. Anagnostaras. Lecture 5 Synaptic Transmission. Introduction to synaptic transmission. Synapses (Gk., to clasp or join) Site of action of most psychoactive drugs. 6.5. Synapses. Know basic terminology: Soma Axon Dendrite Synaptic vesicles Synaptic cleft Postsynaptic

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Psych 181: Dr. Anagnostaras

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  1. Psych 181: Dr. Anagnostaras Lecture 5 Synaptic Transmission

  2. Introduction to synaptic transmission Synapses (Gk., to clasp or join) Site of action of most psychoactive drugs 6.5

  3. Synapses Know basic terminology: • Soma • Axon • Dendrite • Synaptic vesicles • Synaptic cleft • Postsynaptic • Presynaptic • Glia 6.2

  4. Synapses Dendrites & spines 3.10

  5. Synapses Types of cell-cell junctions Tight junctions • membranes fused Gap junctions • close juxtaposition (2-4 nm) • electrical synapse Chemical synapses • synaptic cleft (20-30 nm) • polarized

  6. Multiple types of synapses Vesicle varieties + - 6.3 6.4

  7. Multiple types of synapses Multiple patterns of connectivity • Axodendritic • Dendrodendritic • Axoaxonic • Axosomatic • etc. 6.1

  8. Steps in synaptic transmission • Synthesis • Transport • Storage • Release • Inactivation

  9. Release Excitation-secretion coupling • Depolarization • Open voltage-gated Ca++ channels • Ca++ influx • Bind to Ca++ -calmodulin protein kinase • Phosphorylation of synapsin I • Movement of vesicles to release site • Exocytosis • Diffusion

  10. Exocytosis 6.17

  11. Inactivation Reuptake • transporters Enzymaticdegradation • metabolism • excretion • cycling 8.13

  12. Sample question • In which of the following are the events listed in the correct temporal order (i.e., the temporal order associated with excitation-secretion coupling)? • (a) Depolarization > calcium influx > phosphorylation of synapsin > activation of calcium-calmodulin protein kinase > exocytosis • (b) Depolarization > calcium influx > activation of calcium-calmodulin protein kinase > phosphorylation of synapsin > reuptake > exocytosis • (c) Exocytosis > phosphorylation of synapsin > calcium influx > activation of calcium-calmodulin protein kinase > depolarization > calcium influx • (d) Enzymatic degradation > exocytosis > activation of calcium-calmodulin protein kinase > phosphorylation of synapsin > calcium influx > depolarization • (e) Depolarization > calcium influx > activation of calcium-calmodulin protein kinase > phosphorylation of synapsin > exocytosis > enzymatic degradation

  13. Neurotransmitters Two major types: “Classical” • small water soluble molecules with amine • formed from dietary precursors Neuropeptides • protein synthesis

  14. Neurotransmitters Phenylethylamines • DA, NE, E, tyramine, etc. Indoleamines • 5-HT, tryptamine, melatonin, etc. Cholinergics Amino acids Neuropeptides • Enkephalins, substance P, neurotensin, etc. Nonpeptide hormones

  15. Receptors 6.5

  16. Receptors Classification By Location • Postsynaptic GABA ACH DA

  17. Receptors Classification By Location • Postsynaptic • Autoreceptors GABA ACH DA

  18. Autoreceptors • Presynaptic • Somatodendritic • Terminal • Release-modulating • Synthesis-modulating • Impulse-modulating GABA ACH DA

  19. Receptors Classification: By Transduction Mechanism Drug, transmitter or hormone Outside cell Receptor Transduction Inside cell Membrane Effector

  20. Receptor Superfamilies 1. Ligand-gated channels • binding site coupled to ion channel • transmitter (or drug) gates the channel • ionotropic receptors

  21. Receptor Superfamilies 1. Ligand-gated channels • 2. G protein-coupled • receptor coupled to G protein • G protein activates effector • metabotropic receptors

  22. Ligand-gated channels • Ligand opens channel • Ions flow down conc.gradient • Rapid • Rapidlyreversible 5.9

  23. Ligand-gated channels Examples: Nicotinic acetylcholine receptor • coupled to sodium channel • drugs: nicotine, curare GABAA receptor • coupled to chloridechannel • drugs: sedative-hypnotics

  24. G protein-coupled receptors

  25. G protein-coupled receptors • Large family all with 7 membrane-spanning regions • Receptor coupled to G protein, and G protein stimulates effector • Slower than ion-coupled 6.22

  26. G protein-coupled receptors Two classes: G protein directly coupled to ion channel • effector is ion channel G protein coupled to 2nd messenger system • effector is enzyme that promotes formation of intracellular “second messenger”

  27. G protein-coupled receptors Examples: • Cholinergicmuscarinic • GABA B • 5-HT • Opioid • Dopamine • Norepin-ephrine

  28. Second messengers Are many: • Calcium • cGMP • Phosphoinositides (IP3, diacylglycerol) • cAMP • cAMP (cyclic adenosine 3,5-monophosphate)

  29. 1 cAMP 3 2 4 5 6 7 8 9 6.22

  30. Protein phosphorylation Changes structure/function of protein Consequence depends on function of protein • ion channel proteins • enzymes • cytoskeletal proteins • vesicular proteins • receptors • gene regulatory proteins

  31. Second messengers and protein kinases have many targets from P. Greengard, Science, 2001

  32. from P. Greengard, Science, 2001

  33. Gene regulation Second messengers can alter gene regulation: • Activate transcription factors • Regulate transcription • enhance or supress • If enhance - new gene products

  34. Gene regulation Two phases of gene activation: Initial phase • induction of immediate-early genes (IEGs)(e.g., cfos, c-jun, zif-268, etc.) • protein products initiate 2nd phase Second phase • induction of “late-onset genes” • products that alter cellular function

  35. Gene regulation by cAMP R= regulatory subunit C= catalytic subunit Transcription factor: CREB (cAMP responseelement binding protein) CREB stimulates gene transcription (eg., IEGs) 6.34

  36. Convergence on CREB Multiple signalling pathways can alter gene transcription via same transcription factor 2nd messengers kinases 6.35

  37. Summary Drugs of abuse are very effective in inducing IRGs 6.37 6.37

  38. c-fos mRNA Expression Saline Amphetamine Home Novel

  39. Sites of drug action 6.2

  40. Sample question Which of the following classes of drug action would have in common the effect of increasing synaptic transmission? (a) facilitation of release; block reuptake; inhibition of synthesis (b) blockade of the release modulating autoreceptor; facilitation of release; receptor agonist (c) receptor agonist; receptor antagonist; synthesis inhibition (d) reuptake blocker; facilitation of release; receptor antagonist (e) blocks metabolism; block reuptake; inhibits synthesis

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