Abstract
The reason why neurons synthesize more than one endocannabinoid (eCB) and how this is involved in the regulation of synaptic plasticity in a single neuron is not known. We found that 2-arachidonoylglycerol (2-AG) and anandamide mediate different forms of plasticity in the extended amygdala of rats. Dendritic L-type Ca(2+) channels and the subsequent release of 2-AG acting on presynaptic CB1 receptors triggered retrograde short-term depression. Long-term depression was mediated by postsynaptic mGluR5-dependent release of anandamide acting on postsynaptic TRPV1 receptors. In contrast, 2-AG/CB1R-mediated retrograde signaling mediated both forms of plasticity in the striatum. These data illustrate how the eCB system can function as a polymodal signal integrator to allow the diversification of synaptic plasticity in a single neuron.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Arachidonic Acids / metabolism
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Biophysics
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Calcium / metabolism
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Calcium Channel Blockers / pharmacology
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Calcium Channels, L-Type / metabolism
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Calcium Channels, L-Type / ultrastructure
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Cannabinoid Receptor Modulators / metabolism*
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Cannabinoid Receptor Modulators / pharmacology
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Chromones / pharmacology
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Cyclohexanones / pharmacology
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Electric Stimulation
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Endocannabinoids*
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Enzyme Inhibitors / pharmacology
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Excitatory Amino Acid Antagonists / pharmacology
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Glycerides / metabolism
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In Vitro Techniques
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Long-Term Synaptic Depression / drug effects
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Long-Term Synaptic Depression / physiology
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Neurons / drug effects
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Neurons / physiology*
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Neurons / ultrastructure
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Nimodipine / pharmacology
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Patch-Clamp Techniques
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Piperidines / pharmacology
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Pyrazoles / pharmacology
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Pyridines / pharmacology
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Rats
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Rats, Sprague-Dawley
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Receptor, Cannabinoid, CB2 / metabolism
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Receptor, Cannabinoid, CB2 / ultrastructure
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Receptor, Metabotropic Glutamate 5
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Receptors, Metabotropic Glutamate / metabolism
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Receptors, Metabotropic Glutamate / ultrastructure
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Septal Nuclei / cytology*
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Septal Nuclei / metabolism*
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Signal Transduction / drug effects
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Signal Transduction / physiology*
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Synapses / metabolism
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Synapses / ultrastructure
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TRPV Cation Channels / metabolism
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TRPV Cation Channels / ultrastructure
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Time Factors
Substances
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7-(hydroxyimino)cyclopropan(b)chromen-1a-carbxoylic acid ethyl ester
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Arachidonic Acids
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Calcium Channel Blockers
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Calcium Channels, L-Type
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Cannabinoid Receptor Modulators
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Chromones
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Cnr2 protein, rat
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Cyclohexanones
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Endocannabinoids
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Enzyme Inhibitors
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Excitatory Amino Acid Antagonists
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Glycerides
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Grm5 protein, rat
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L-type calcium channel alpha(1C)
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Piperidines
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Pyrazoles
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Pyridines
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Receptor, Cannabinoid, CB2
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Receptor, Metabotropic Glutamate 5
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Receptors, Metabotropic Glutamate
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TRPV Cation Channels
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Trpv1 protein, rat
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AM 251
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Nimodipine
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6-methyl-2-(phenylethynyl)pyridine
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1,6-bis(cyclohexyloximinocarbonyl)hexane
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glyceryl 2-arachidonate
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Calcium