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Nens220, Lecture 7 Plasticity and Homeostasis

Nens220, Lecture 7 Plasticity and Homeostasis. John Huguenard. Electrochemical signaling. Most CA3-CA1 connections unitary. Sorra and Harris, J Neurosci. 13:3736, 1993. CA3->CA1 Single vesicle synapses. Bolshakov & Siegelbaum, Science. 1995 269:1730-4.

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Nens220, Lecture 7 Plasticity and Homeostasis

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  1. Nens220, Lecture 7 Plasticity and Homeostasis John Huguenard

  2. Electrochemical signaling

  3. Most CA3-CA1 connections unitary Sorra and Harris, J Neurosci. 13:3736, 1993

  4. CA3->CA1 Single vesicle synapses Bolshakov & Siegelbaum, Science. 1995 269:1730-4

  5. Short term plasticity at CA3->CA1: evidence for changes in p, not q. Bolshakov & Siegelbaum, Science. 1995 269:1730-4

  6. mEPSCs are about the same size as unitary events. Bolshakov & Siegelbaum, Science. 1995 269:1730-4

  7. Evidence for multivesicular release Blocking Glu uptake with TBOA did not affect this result, suggesting that Pr does not affect spillover, but rather causes MVR Christie and Jahr, J Neurosci. 26:210, 2006

  8. Evidence saturation/monovesicular release Plant et al., Nature Neuroscience 9, 602 - 604 (2006)

  9. Short term plasticity • Dynamic changes in release probability • Likely mechanisms • Ca2+ accumulation in synaptic terminals • Altered vesicle availability • To implement • update Prel upon occurrence of a spike • then continue to calculate state of Prel dependent on P0 (resting probability) and tP(rel) Fuhrmann et al J Neurophysiol 87:140, 2002

  10. Longer term plasticity • bidirectional • LTP • LTD • Both IE and synaptic strength may change • Implicated in learning and memory

  11. LTP

  12. LTP • Robust in hippocampus • Readily evoked and recorded with extracellular electrodes • Evoked by tract stimulation: simultaneous activation of many axons • There are more subtle (and in my view more interesting) versions of LTP

  13. Spike timing dependent plasticity in Xenopus tectal neurons, retinal stimulation Requires NMDA R Requires post-synaptic spiking Hyperpolarization not suff. LTD Zhang et al. 1998

  14. STDP in dispersed hippocampal cultures – Paired recordings Bi and Poo 1998

  15. Spike timing dependent plasticity in rat visual cortex LII-III FROEMKE & DAN, 2002

  16. Natural stimuli & STDP FROEMKE & DAN, 2002

  17. Natural stimuli & STDP Further reading: Coactivation and timing-dependent integration of synaptic potentiation and depression, Bi Lab, 2005 FROEMKE & DAN, 2002

  18. Back propagation APs and LTP Ca dependent - L channels Na dependent - back prop Often NMDAR dependent Calcium spatio-temporal dynamics: Calcineurin ~ LTD CaMKII ~ LTP Magee and Johnston, 1997

  19. Homeostatic Plasticity: Turrigiano et al Science 264:974, 1994

  20. The need for homeostatic synaptic plasticity Turrigiano 2008

  21. TNF-a dependent synaptic scaling Stellwagen & Malenka, Nature 440:1054, 2006

  22. TNF-a dependent synaptic scaling Stellwagen & Malenka, Nature 440:1054, 2006

  23. 250 pA 2.5 ms 250 pA Fran Shen

  24. Dynamic-Clamp: Artificial Autaptic IPSCs Based on Fuhrmann, et al. J Neurophysiol 87: 140–148, 2002

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