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Nens220, Lecture 6 Interneuronal communication

Nens220, Lecture 6 Interneuronal communication. John Huguenard. Electrochemical signaling. Synaptic Mechanisms. Ca 2+ dependent release of neurotransmitter Normally dependent on AP invasion of synaptic terminal Probabilistic. Probabilistic release . Synaptic release is unreliable

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Nens220, Lecture 6 Interneuronal communication

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  1. Nens220, Lecture 6 Interneuronal communication John Huguenard

  2. Electrochemical signaling

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

  4. Probabilistic release • Synaptic release is unreliable • Action potential invasion does not necessary evoke release • Net response is product of number of terminals (or release sites, n ), size of unitary response (q), and probability (p) of release at each terminal • N varies between 1 and 100 • p between 0 and 1 • q is typically on the order of 0.1 to 1 nS

  5. Binomial probability

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

  7. 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

  8. Three major classes of ligand gated conductances: ligands • Excitatory • Glutamate • AMPA/Kainate receptors (fast) • NMDA receptors (slow) • Inhibitory • Gamma amino butyric acid GABAA receptors

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

  10. 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

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

  12. Spike/PSP interactions Hausser et al. Science Vol. 291. 138 - 141

  13. EPSC/AP coupling Galaretta and Hestrin Science 292, 2295 (2001);

  14. EPSP/spike coupling II Galaretta and Hestrin Science 292, 2295 (2001);

  15. 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

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

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

  18. Inhibitory 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

  19. 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

  20. mReceptors, cont’d. • 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

  21. Electrotonic synapses • Transmembrane pores • Resistive connection between the intracellular compartments of adjacent neurons • Prominent in some inhibitory networks

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

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

  24. 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)

  25. 250 pA 2.5 ms 250 pA Fran Shen

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

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