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The Journal of Neuroscience, June 20, 2007, 27(25):6781-6787; doi:10.1523/JNEUROSCI.0280-07.2007

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Cellular/Molecular
Combined Activation of L-Type Ca²⁺ Channels and Synaptic Transmission Is Sufficient to Induce Striatal Long-Term Depression

Louise Adermark and David M. Lovinger

Section on Synaptic Pharmacology, Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892

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

Changes in synaptic strength at striatal synapses, such as long-term depression (LTD), may be involved in striatal-based learning and memory. Several molecular mechanisms have been implicated in striatal LTD, but it is not clear which mechanisms are crucial for LTD induction. We found that the activation of L-type calcium channels by 2,5-dimethyl-4-[2-(phenylmethyl)benzoyl]-¹H-pyrrole-3-carboxylic acid methylester (FPL64176), combined with modest postsynaptic depolarization and synaptic activation, is sufficient to induce robust LTD (FPL–LTD). The L-channel activator 1,4-dihydro-2,6-dimethyl-5-nitro-4-[2(trifluoromethyl)phenyl]pyridine-3-carboxylic acid methyl ester (Bay K 8644) has a similar action. FPL–LTD occludes LTD induced by high-frequency stimulation (HFS–LTD) and requires elevated postsynaptic calcium and retrograde endocannabinoid signaling, properties similar to those of HFS–LTD. In contrast, FPL–LTD does not require the activation of metabotropic glutamate receptors (mGluRs), phospholipase C, or dopamine D₂ receptors. FPL–LTD induction also requires afferent stimulation. These findings suggest a scenario in which L-type calcium channel activation is a crucial switch for LTD induction, and mGluRs and D₂ receptors can be bypassed if this channel is activated.

Key words: synaptic plasticity; basal ganglia; dopamine; glutamate; endocannabinoid; presynaptic mechanisms

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Received Jan. 22, 2007; revised May 14, 2007; accepted May 15, 2007.

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

Related articles in J. Neurosci.:

A Molecular Switch for Induction of Long-Term Depression of Corticostriatal Transmission

Mazen A. Kheirbek
J. Neurosci. 2007 27: 9824-9825. [Full Text]  

This article has been cited by other articles:

				L. Adermark and D. M Lovinger Frequency-Dependent Inversion of Net Striatal Output by Endocannabinoid-Dependent Plasticity at Different Synaptic Inputs J. Neurosci., February 4, 2009; 29(5): 1375 - 1380. [Abstract] [Full Text] [PDF]

				W. Shen, M. Flajolet, P. Greengard, and D. J. Surmeier Dichotomous Dopaminergic Control of Striatal Synaptic Plasticity Science, August 8, 2008; 321(5890): 848 - 851. [Abstract] [Full Text] [PDF]

				L. Adermark and D. M. Lovinger Retrograde endocannabinoid signaling at striatal synapses requires a regulated postsynaptic release step PNAS, December 18, 2007; 104(51): 20564 - 20569. [Abstract] [Full Text] [PDF]

				M. A. Kheirbek A Molecular Switch for Induction of Long-Term Depression of Corticostriatal Transmission J. Neurosci., September 12, 2007; 27(37): 9824 - 9825. [Full Text] [PDF]

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