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The Journal of Neuroscience, February 4, 2009, 29(5):1375-1380; doi:10.1523/JNEUROSCI.3842-08.2009

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Brief Communications
Frequency-Dependent Inversion of Net Striatal Output by Endocannabinoid-Dependent Plasticity at Different Synaptic Inputs

Louise Adermark^1,2 and David M Lovinger¹

¹Section on Synaptic Pharmacology, Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism/National Institutes of Health, Bethesda, Maryland 20892, and ²Addiction Biology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, 405 30 Gothenburg, Sweden

Correspondence should be addressed to David M. Lovinger, Section on Synaptic Pharmacology, Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism/National Institutes of Health, 5625 Fishers Lane, TS-13, Bethesda, MD 20892. Email: lovindav{at}mail.nih.gov

Understanding how striatal neurons integrate glutamatergic and GABAergic inputs is essential for understanding the control of movement and the formation of striatal-based memories. Here we show that GABAergic synapses on striatal medium spiny neurons (MSNs) are more sensitive than glutamatergic synapses on the same cells to endocannabinoid (eCB) signaling, and that protocols that induce short-lasting cannabinoid 1 receptor (CB₁R)-dependent depression at glutamatergic synapses are sufficient to induce long-term depression (LTD) at GABAergic synapses. We also show that the frequency and duration of glutamatergic input are strong determinants of the net effect of eCB signaling, and key factors in determining if LTD has a net disinhibitory or inhibitory action in striatum. Plastic changes in net output from striatal MSNs are thus a complex function of disinhibitory and inhibitory LTD combined with other forms of synaptic plasticity such as long-term potentiation at excitatory synapses.

Key words: anandamide; basal ganglia; LTD; synaptic plasticity; GABA; glutamate

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Received Aug. 12, 2008; revised Dec. 3, 2008; accepted Dec. 29, 2008.

Correspondence should be addressed to David M. Lovinger, Section on Synaptic Pharmacology, Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism/National Institutes of Health, 5625 Fishers Lane, TS-13, Bethesda, MD 20892. Email: lovindav{at}mail.nih.gov

This article has been cited by other articles:

				S.-y. Zhang, M. Xu, Q.-l. Miao, M.-m. Poo, and X.-h. Zhang Endocannabinoid-Dependent Homeostatic Regulation of Inhibitory Synapses by Miniature Excitatory Synaptic Activities J. Neurosci., October 21, 2009; 29(42): 13222 - 13231. [Abstract] [Full Text] [PDF]

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