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Integration of neural plasticity

Integration of neural plasticity. Multiple mechanisms per synapse Multiple synapses per cell Multiple cells per function Examples Tritonia escape response Aplysia gill withdrawal reflex Leech central pattern generator Autonomic control of hypertrophy. Tritonia/Aplysia flight.

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Integration of neural plasticity

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  1. Integration of neural plasticity • Multiple mechanisms per synapse • Multiple synapses per cell • Multiple cells per function • Examples • Tritonia escape response • Aplysia gill withdrawal reflex • Leech central pattern generator • Autonomic control of hypertrophy

  2. Tritonia/Aplysia flight • Stereotypical swim response • Phasic, fixed duration • Simple pattern generator • Individually identified neurons • Simple connectivity Getting, 1980

  3. Metabotropic Neuromodulation • DSI stimulation triggers fast and slow depolarization • Slow depolarization is GTP dependent • Blocked by non-hydrolyzable GDP-b-S Recording Stimulation

  4. Recording Stimulation Tritonia Metabotropic Neuromodulation • DSI stimulation triggers fast and slow depolarization • Slow depolarization is GTP dependent • Blocked by non-hydrolysable GDP-b-S Fast Ionotropic depolarization Slow metabotropic depolarization Blocks metabotropic process

  5. Neuromodulation • Multiple receptor types at a single synapse induce divergent actions • Fast/slow • Excitatory/inhibitory • Multiple substance release at a single synapse induce multiple actions • Multiple neurotransmitters • Serotonin/norepinepherine/dopamine • Neuromodulatory peptides • Somatostatin, substance P, vasopressin • Accommodation/facilitation over sec - min

  6. UTMB Magazine Aplysia gill withdrawal • Gill & siphon normally exposed for metabolite exchange • Tactile/nocioceptive stimulation triggers withdrawal • Similar pathways in all species Gill Mantle Siphon Tail Leonard & Edstrom, 2004

  7. Neural Circuit • Sensory neurons (SN) • Motorneurons (L7, LDg1, LDg2…) • Interneurons (ex: L16, L25) SN L25 L16 INin INin L7 LDG1 LDG2 Leonard & Edstrom, 2004

  8. Habituation • EPSP amplitude declines during habituation • Quantal • SN goes from releasing 3 NT vesicles to 0 Est # vesicle release Record post-synaptic EPSP amplitude in response to sensory nerve stimulus, construct a histogram, and look for discrete quanta Number observed EPSP Amplitude (uV) Castellucci & Kandel, 1974

  9. Habituation • Presynaptic neurotransmitter vesicles separate from the cell membrane • Depletion • Ca2+ dose-dependent untethering (calpain), channel inactivation (CaV), recruitment of SV (PKC) (?) Naïve sensory terminal Habituated sensory terminal Note: greater distance between vesicles and membrane. Bailey & Chen, 1988

  10. Sensitization • EPSP amplitude is potentiated by prior stimulation of separate pathway Siphon Tail SN SN L25 L29 L16 L7 LDG1 LDG2 Leonard & Edstrom, 2004

  11. Sensitization • Tail interneuronal collaterals synapse with siphon interneurons • Facilitating interneuron L29 • Serotonergic + SCP • Presynaptic • Serotonin • GaSACPKA--|KIRKIR--|CaVNT release • SCP Sensory neuron recordings PSP and spike width show habituation Until L29 is briefly tetanized Hawkins, 1981

  12. Sensitization • Amplification within sensitization • Single stimulus  hours of increased gain • Multiple stim  days • Rate/dose decoding • PKA: fast acting, slow transport • Local K/Ca channels • Distributed K/Ca channels • Nuclear import, CREB

  13. Long term sensitization • CREB induces new synapse formation by formation of sensory collaterals. Stimulation of cultured neuron results in rapid development of a new dendritic spine Goldin, et al., 2001

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