HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 102/2/1160    most recent 00266.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Kellogg, R. Articles by Straiker, A. PubMed PubMed Citation Articles by Kellogg, R. Articles by Straiker, A.

Cannabinoid CB₁ Receptor-Dependent Long-Term Depression in Autaptic Excitatory Neurons

¹Department of Anesthesiology, University of Washington, Seattle, Washington; and ²Department of Psychological and Brain Sciences, Gill Center for Biomolecular Science, Indiana University, Bloomington, Indiana

Submitted 25 March 2009; accepted in final form 29 May 2009

Long-term depression (LTD) of synaptic signaling—lasting from tens of minutes to hours or longer—is a widespread form of synaptic plasticity in the brain. Neurons express diverse forms of LTD, including autaptic LTD (autLTD) observed in cultured hippocampal neurons, the mechanism of which remains unknown. We have recently reported that autaptic neurons express both endocannabinoid-mediated depolarization-induced suppression of excitation (DSE) and metabotropic suppression of excitation (MSE). We now report that activating cannabinoid CB₁ receptors is necessary for the induction of autLTD. Most surprisingly, CB₁ does not induce autLTD via the G_i/o proteins typically activated by this receptor nor with G_s. Rather, the requirements of presynaptic phospholipase C and filled calcium stores suggest G_q. In autLTD, a 3- to 4-min activation of the receptor by the endocannabinoid 2-arachidonoyl glycerol leads to prolonged inhibition while leaving short-term inhibition (e.g., DSE) intact. autLTD requires activation of both metabo- and ionotropic glutamate receptors. autLTD also requires MEK/ERK activation. Under certain conditions, one or more DSE stimuli will elicit autLTD. It is becoming evident that cannabinoids mediate multiple forms of plasticity at a single synapse, stretching temporally from tens of seconds (DSE/MSE) to tens of minutes (autLTD) to hours (CB₁ desensitization). Our findings imply a remarkable flexibility for the cannabinoid signaling system whereby discrete mechanisms of CB₁ activation within a single neuron yield temporally and mechanistically distinct forms of plasticity.

This article has been cited by other articles:

				A. Straiker, S. S.-J. Hu, J. Z. Long, A. Arnold, J. Wager-Miller, B. F. Cravatt, and K. Mackie Monoacylglycerol Lipase Limits the Duration of Endocannabinoid-Mediated Depolarization-Induced Suppression of Excitation in Autaptic Hippocampal Neurons Mol. Pharmacol., December 1, 2009; 76(6): 1220 - 1227. [Abstract] [Full Text] [PDF]