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Postsynaptic endocannabinoid release is critical to long-term depression in the striatum

Nature Neuroscience volume 5, pages 446451 (2002) | Download Citation

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Abstract

The striatum functions critically in movement control and habit formation. The development and function of cortical input to the striatum are thought to be regulated by activity-dependent plasticity of corticostriatal glutamatergic synapses. Here we show that the induction of a form of striatal synaptic plasticity, long-term depression (LTD), is dependent on activation of the CB1 cannabinoid receptor. LTD was facilitated by blocking cellular endocannabinoid uptake, and postsynaptic loading of anandamide (AEA) produced presynaptic depression. The endocannabinoid necessary for striatal LTD is thus likely to be released postsynaptically as a retrograde messenger. These findings demonstrate a new role for endocannabinoids in the induction of long-term synaptic plasticity in a circuit necessary for habit formation and motor control.

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Acknowledgements

We thank T. Möykkynen for technical assistance, G. Kunos, K. Mackie and D. Winder for helpful comments during manuscript preparation, and A. Zimmer for providing CB1+/− mice. This work was supported by NIH grants NS30470 (D.M.L.) and DA05923 (G.L.G.).

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Author notes

    • Gregory L. Gerdeman

    Present address: Department of Pharmacology, The University of Arizona Health Sciences Center, Tucson, Arizona 85724-5050, USA

    • Jennifer Ronesi
    •  & David M. Lovinger

    Present address: Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, 158H Park 5 Building, Rockville, Maryland 20852, USA

Affiliations

  1. Departments of Molecular Physiology & Biophysics and Pharmacology, and Center for Molecular Neuroscience, Vanderbilt University, Nashville, Tennessee 37232-0615, USA

    • Gregory L. Gerdeman
    • , Jennifer Ronesi
    •  & David M. Lovinger

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The authors declare no competing financial interests.

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Correspondence to David M. Lovinger.

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DOI

https://doi.org/10.1038/nn832

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