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Synapses

Synapses. Interneuronal communication. Hormone "Volume" Ephapse Juxtapositional exchange Gap junction Chemical synapse depolarisation modulation retrograde (NOS, TFs). Mammalian electrical synapses. Mesencephalic n. of V Dieter's vestibular n. Inf. olive Retina. Electrical coupling

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Synapses

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  1. Synapses

  2. Interneuronal communication • Hormone • "Volume" • Ephapse • Juxtapositional exchange • Gap junction • Chemical synapse • depolarisation • modulation • retrograde (NOS, TFs)

  3. Mammalian electrical synapses • Mesencephalic n. of V • Dieter's vestibular n. • Inf. olive • Retina • Electrical coupling • Uncoupled during AP

  4. Classical Neurotransmitter • Contained in presynaptic terminal • Synthesized in presynaptic neurone • Released in response to stimulus in presynaptic neurone • Elicits a response in the postsynaptic neurone

  5. Neurotransmitters • Amine • Amino acid (Glut, Gly, GABA, Aspartatae) • Monoamine • Catecholamine (DA, Adr, NA) • 5-HT • Histamine • Peptide • Enkephalins, endorphins • Gastrin, CCK, VIP, substance P • Heterogeneous • ACh, NO, CO, ATP, adenosine, D-serine

  6. Synaptic receptor classification

  7. Neurotransmitters

  8. Gs

  9. Neurotransmitters: Effects on postsynaptic membrane • Ion channel opening • Depolarisation Na, Ca • Hyperpolarisation K • Restoration to resting Cl • Second messenger Ca, cAMP, IP3 • Receptor/channel regulation • Phosphorylation, activation, inactivation • Transcription factor activation • Chemical change • Structural change

  10. Second Messengers • Calcium • Cyclic AMP • Phosphodiesterase • Adenylate cyclase • II bg subunit activated • III,IV Calcium activated • V, VI Calcium inhibited • Nitric oxide • Inositol trisphosphate • ras, fos, jun

  11. Neurone Fire new AP (Na) Alter sensitivity of synapse Apoptosis Muscle Skeletal muscle contraction (Ca:troponin) Smooth muscle contraction Vascular (a) bronchus (b2) ciliary, gut , bladder (M) Cardiac leak current (heart rate, b1) Other metabolic cells Glycogenolysis Platelet aggregation Lipolysis ↑ Gastric acid Neurotransmitters:Cellular functions

  12. Desensitisation Phosphorylation by PKA bARK b-arrestin Downregulation Internalisation ↑ Degradation ↓ Synthesis Receptor structure GluR RNA editing AMPA splicing Anatomical change ? LTP Synaptic modification

  13. Neurotransmitters:Global effects in the CNS • Glutamate excitatory • GABA inhibitory, epilepsy • Glycine inhibitory (spinal cord) • NA, 5-HT affect • ACh memory, motor, vomiting • DA psychosis, motor, vomiting • Endorphins addiction, ↓ pain

  14. Global neurotransmitter pathways Ach DA NA Parietal Striatum Cing Frontal HT Septal n. Ventral tegmental area Amyg HC Basal forebrain n. SNPC Tegmentum Lateral tegmental n.

  15. Metabo- and Ionotropic receptors

  16. Presynaptic Calcium restoration • Buffering by Calmodulin • Dilution • Extrusion by ATPase

  17. GABAA Cl-channel binding • GABA • Benzodiazepines • Barbiturates • Steroid • Zn • Picrotoxinin-TBPS • Strychnine

  18. NMDA receptor binding • Glutamate • Polyamine • Zn • Glycine (essential co-agonist) • Mg • PCP

  19. Ca excitotoxicity • ODC • NOS • PLA2 • Proteases • Endonucleases • Mitochondrial damage

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