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Nens220, Lecture 4 Interneuronal communication

Nens220, Lecture 4 Interneuronal communication. John Huguenard. Synaptic Mechanisms. Ca 2+ dependent release of neurotransmitter Normally dependent on AP invasion of synaptic terminal Probabilistic. Short term plasticity. Dynamic changes in release probability Likely mechanisms

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Nens220, Lecture 4 Interneuronal communication

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  1. Nens220, Lecture 4 Interneuronal communication John Huguenard

  2. Synaptic Mechanisms • Ca2+ dependent release of neurotransmitter • Normally dependent on AP invasion of synaptic terminal • Probabilistic

  3. 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)

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

  5. LTP

  6. LTP • Robust in hippocampus • Readily evoked and recorded with extracellular electrodes • Evoked by tract stimulation: simultaneous activation of many axons • More subtle (and interesting) versions of LTP

  7. Spike timing dependent plasticity in Xenopus tectal neurons, retinal stimulation Zhang et al. 1998

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

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

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

  11. 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

  12. STDP, critically dependent on a narrow (~20 ms) timing window. Bi and Poo 1998

  13. Presynaptic receptor mediated alterations • Mainly metabotropic • An exception is nicotinic AchR • Homosynaptic “autoreceptors” • Heterosynaptic receptors

  14. Postsynaptic properties: ionotropic receptors • Ligand gated receptors • Directly gated by neurotransmitter – ion pores • Can be modeled analogously to voltage-gated channels

  15. The probability of a ligand gated channel be open (Ps) will depend on: • on and off rates for the channel • With the on rate dependent on neurotransmitter concentration • This can be approximated by a brief (e.g. 1ms) increase, followed by an instantaneous return to baseline

  16. Three major classes of ligand gated conductances • GABAA • Fast IPSP signaling • trise < 1ms • tdecay : 1.. 200 ms !, modulable • Cl- dependent • EGABAA range: –45 .. –90 mV • Highly dependent on [Cl-]i • Which is in turn activity dependent • NEURON can track this

  17. AMPA (glutamate) • Fast EPSP signaling • trise < 1ms • tdecay : 1..10 ms • Cation dependent • EAMPA 0 mV.

  18. Ca2+ permeability: AMPAR • Depends on molecular composition • GluR2 containing receptors are Ca2+ impermeable • Unless unedited • Prominent in principle cell (e.g. cortical pyramidal neuron) synapses • GluR1,3,4 calcium permeable • Calcium permeable AMPA receptors more common in interneurons

  19. AMPAR have significant desensitization • Contributes to rapid EPSC decay at some synapses

  20. NMDA (glutamate) • EPSP signaling, slower than with AMPA • trise : 2-50 ms • tdecay : 50-300 ms • cation dependent • ENMDA 0 mV • Significant Ca2+ permeability • NMDAR - necessary for many forms of long-term plasticity

  21. NDMAR Blocked by physiological levels of [Mg2+]o • Voltage and [Mg2+]o dependent • Depolarization relieves block

  22. Kainate receptors (glutamate) • Roles are less well defined than AMPA/NMDA

  23. Metabotropic receptors • Many classes • Conventional neurotransmitters, GABA, glutamate • Peptide neurotransmitters, e.g. NPY, opioids, SST • Often activate GIRKS • G-protein activated, inwardly-rectifying K+ channels

  24. mReceptors • Inhibitory, hyperpolarizing responses. • Can be excitatory, • e.g. Substance P closes GIRKS • Slow time course • e.g. GABAB responses can peak in > 30 ms and last 100s of ms • Presynaptic & negatively coupled to GPCRs

  25. Electrotonic synapses • Transmembrane pores • Connect the intracellular compartments of adjacent neurons • Prominent in some inhibitory networks

  26. Perisynaptic considerations • Neurotransmitter uptake by glia or neurons • Diffusion • heterosynaptic effects • extrasynaptic receptors • Hydrolysis

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