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Postsynaptic TRPV1 triggers cell type–specific long-term depression in the nucleus accumbens

Nature Neuroscience volume 13, pages 1519–1525 (2010)Cite this article

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Abstract

Synaptic modifications in the nucleus accumbens (NAc) are important for adaptive and pathological reward-dependent learning. Medium spiny neurons (MSNs), the major cell type in the NAc, participate in two parallel circuits that subserve distinct behavioral functions, yet little is known about differences in their electrophysiological and synaptic properties. Using bacterial artificial chromosome transgenic mice, we found that synaptic activation of group I metabotropic glutamate receptors in NAc MSNs in the indirect, but not direct, pathway led to the production of endocannabinoids, which activated presynaptic CB1 receptors to trigger endocannabinoid-mediated long-term depression (eCB-LTD) as well as postsynaptic transient receptor potential vanilloid 1 (TRPV1) channels to trigger a form of LTD resulting from endocytosis of AMPA receptors. These results reveal a previously unknown action of TRPV1 channels and indicate that the postsynaptic generation of endocannabinoids can modulate synaptic strength in a cell type–specific fashion by activating distinct pre- and postsynaptic targets.

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Figure 1: Electrophysiological properties of direct (D2+) and indirect (D2−) pathway MSNs in the NAc core.
Figure 2: D2+ MSNs but not D2– NAc MSNs show mGluR5-dependent LTD.
Figure 3: D2+ MSNs show forms of LTD that are dependent and independent of CB1 receptors and RIM1α.
Figure 4: TRPV1 channels trigger LTD at synapses on D2+ NAc MSNs.
Figure 5: Trpv1−/− mice lack CB1 receptor-independent LFS LTD at synapses on D2+ NAc MSNs.
Figure 6: Postsynaptic TRPV1 channels trigger LTD in D2+ NAc MSNs.
Figure 7: Effects of in vivo cocaine administration on LFS LTD in NAc D2+ MSNs and locomotor behavior in Trpv1−/− mice.

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Acknowledgements

We thank members of the Malenka lab for their comments. This work was supported by grants from the National Institute on Drug Abuse (DA009264, DA008227 to R.C.M.; 5F32DA023741-2 to B.A.G.).

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Authors and Affiliations

  1. Department of Psychiatry and Behavioral Sciences, Nancy Pritzker Laboratory, Stanford University School of Medicine, Palo Alto, California, USA

    Brad A Grueter, Gabor Brasnjo & Robert C Malenka

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  1. Brad A Grueter
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Contributions

B.A.G., G.B. and R.C.M. designed the experiments, interpreted the results and wrote the paper. B.A.G. and G.B. performed all of the experiments and analyzed the results.

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Correspondence to Robert C Malenka.

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The authors declare no competing financial interests.

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Grueter, B., Brasnjo, G. & Malenka, R. Postsynaptic TRPV1 triggers cell type–specific long-term depression in the nucleus accumbens. Nat Neurosci 13, 1519–1525 (2010). https://doi.org/10.1038/nn.2685

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