Bipn140 Lect 8 Figs Oct2010

Bipn140 Lect 8 Figs Oct2010 - BIPN 140: Cellular...

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Unformatted text preview: BIPN 140: Cellular Neurobiology LECTURE #8: Synaptic Transmission II [Website: http://www.biology.ucsd.edu/classes/bipn140.FA10] INSTRUCTORS Nicholas C. Spitzer (nspitzer@ucsd.edu) Darwin K. Berg (dberg@ucsd.edu) ANNOUNCEMENTS Midterm Graded Exams: Pick up from box on 3rd flr, Pac Hall, across from elevators. Keys & Grade Cut-Offs: See posting on website after class. Unsigned exams: K. McPherson, 3100E Pac Hall, M-F 1:30-3pm. Fig 5.16a Activation of ACh receptors at NMJ synapses Fig 5.16b Activation of ACh receptors at NMJ synapses Fig 5.16c Activation of ACh receptors at NMJ synapses Fig 5.17a Influence of postsynaptic membrane potential on end plate currents Fig 5.17b Influence of postsynaptic membrane potential on end plate currents Fig 5.17c Influence of postsynaptic membrane potential on end plate currents Fig 5.18a/b Effect of ion channel selectivity on reversal potential Fig 5.18c/d Effect of ion channel selectivity on reversal potential Fig 5.19a/b Na+ & K+ movements during EPCs & EPPs Fig 5.19c/d Na+ & K+ movements during EPCs & EPPs Fig 5.20a/b Reversal & threshold potentials determine postsynaptic excitation & inhibition Fig 5.20c/d Reversal & threshold potentials determine postsynaptic excitation & inhibition Fig 5.21a Summation of PSPs Fig 5.21b Summation of PSPs Fig 5.22 Events from neurotransmitter release to postsynaptic excitation or inhibition Fig 5.23a NT effects on postsynaptic cell via ionotropic or metabotropic receptors Fig 5.23b NT effects on postsynaptic cell via ionotropic or metabotropic receptors Endogenous Cannabinoids Mediate Retrograde Signaling at Hippocampal Synapses by Rachel I. Wilson & Roger A. Nicoll Nature 410:588-592 (2001) BACKGROUND Endogenous cannabinoids, e.g. anandamide (as well as THC from marijuana) diffuse across cell membranes and activate receptors in hippocampal interneurons that depress GABA release. Depolarization of hippocampal pyramidal neurons suppresses GABAergic IPSPs the neurons receive, a phenomenon called “Depolarization-induced Suppression of Inhibition” or DSI. DSI was thought to represent a retrograde effect of the postsynaptic neuron onto presynaptic inhibitory terminals, but the mechanism was unknown. EXPERIMENTS Induce DSI by depolarizing a hippocampal pyramidal neuron with a patch pipette, and record the changes that occur in IPSPs elicited by stimulating interneuron input to the neuron. Test the effects of compounds that block cannabinoid receptors to see if they block DSI. Similarly, test compounds that activate cannabinoid receptors to see if they mimic DSI. Determine if the cannabinoid effect is likely to be presynaptic, e.g affects mEPSC frequency but not mEPSC amplitude. Fig. 1. DSI requires endogenous cannabinoids. [A] [B] [C] [D] [E] AM251, a blocker of cannabinoid receptors, prevents DSI, while the control (DMSO) has no effect. Two cannabinoid receptor blockers show the same effect (AM251 and SR141716). DSI is otherwise stable in control neurons over this time period. A cannabinoid receptor antagonist diminishes DSI, causing IPSC amplitude to return to normal. Cannabinoid receptor agonist WIN55212-2 induces IPSC amplitude, like DSI. Fig 3a-d: WIN, a cannabinoid receptor agonist, depresses IPSCs by the same mechanism that DSI does [A] WIN, a cannabinoid receptor agonist, increases paired-pulse ratio (PPR), consistent with a presynaptic effect. [B] Like WIN, DSI also increases PPR. [C, D] WIN decreases mIPSC frequency (in TTX), again consistent with a presynaptic effect. RESULTS Blockers of cannabinoid receptors blocked DSI expression; agonists of the receptors mimicked DSI. Both the agonists and DSI altered PPR suggesting they both acted on presynaptic machinery in GABAergic (inhibitory) terminals innervating the pyramidal neuron. And in figures not shown above, DSI was shown to “spread” locally, affecting IPSP amplitude in nearby neurons, exactly as predicted for a diffusible membrane-permeant regulator like cannabinoids. TAKEHOME: DSI relies on the retrograde (back across the synapse) transfer of cannabinoids which inhibit GABA release from presynaptic terminals, thereby reducing the evoked IPSC seen in the postsynaptic pyramidal neuron. Globally applied cannabinoids, e.g. THC, can be expected to globally diminish inhibitory activity and alter information processing and system output. ...
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This note was uploaded on 10/30/2010 for the course BIPN BIPN 140 taught by Professor Spitzer during the Fall '07 term at UCSD.

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