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Neurodegenerative disorders

Pathways to treatment

Nature Reviews Neuroscience volume 8, pages 287–299 (2007)Cite this article

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The researchers used transgenic mice strains that expressed green fluorescent protein (GFP) in medium spiny neurons (MSNs) of either the direct or indirect pathway to visualize these cells in brain slices. Whole-cell voltage-clamp recordings revealed that synapses onto indirect pathway MSNs have a higher neurotransmitter release probability and a higher density of NMDA (N-methyl-D-aspartate) receptors than those onto direct-pathway MSNs. Indirect pathway MSNs have increased excitability in response to depolarizing currents.

These properties indicated that synaptic plasticity might be greater at indirect pathway synapses. Indeed, long-term depression (LTD) could be induced at indirect pathway synapses, but not at direct pathway synapses. LTD was blocked by a cannabinoid CB1 receptor antagonist, showing that endocannabinoids released by MSNs are crucial. Presynaptic terminals at both direct and indirect pathway synapses express CB1 receptors, indicating that the two pathways probably differ in terms of the synthesis or release of endocannabinoids.

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Change history

  • 06 July 2018

    This article was initially published with an incorrect DOI. A new DOI has been assigned and registered at Crossref, and has been corrected in the article.

ORIGINAL RESEARCH PAPER

  1. Kreitzer, A. C. & Malenka, R. C. Endocannabinoid-mediated rescue of striatal LTD and motor deficits in Parkinson's disease models. Nature 8 Feb 2007 (doi:10.1038/nature05506)

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  1. Katherine Whalley
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Whalley, K. Pathways to treatment. Nat Rev Neurosci 8, 287–299 (2007). https://doi.org/10.1038/nrn2107x

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  • DOI: https://doi.org/10.1038/nrn2107x

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