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Synaptic plasticity

A depressing TRP

Nature Reviews Neuroscience volume 9, page 324 (2008)Cite this article

The authors' discovery of this new role for TRPV1 was unexpected. They set out to characterize the LTD at excitatory synapses on hippocampal interneurons that follows high-frequency stimulation (HFS) of excitatory afferents. Using rat brain slices and electrophysiological techniques, they found that this form of LTD requires the activity of postsynaptic metabotropic glutamate receptors (mGluRs). At many synapses, mGluRs mediate LTD by releasing retrograde messengers that can act on presynaptic cannabinoid 1 (CB1) receptors to reduce glutamate release. However, blocking CB1 receptors did not prevent this form of LTD, suggesting that another mechanism was involved.

As TRPV1 is activated by many of the same retrograde messengers that signal through CB1 receptors, the authors investigated whether it might be involved in the observed LTD. Application of capsaicin, a specific TRPV1 agonist, mimicked the HFS-induced LTD, whereas the induction of LTD was prevented by the application of TRPV1 antagonists. Furthermore, in slices taken from Trpv1−/− mice, LTD could not be induced by HFS or capsaicin treatment. Application of capsaicin induced an inward current in wild-type hippocampal pyramidal cells but not in interneurons, indicating that the TRPV1 channels are not located on the postsynaptic interneuron but might be located in the presynaptic terminals of pyramidal cells.

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ORIGINAL RESEARCH PAPER

  1. Gibson, H. E., Edwards, J. G., Page, R. S., Van Hook, M. J. & Kauer, J. A. TRPV1 channels mediate long-term depression at synapses on hippocampal interneurons. Neuron 57, 746–759 (2008)

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Authors
  1. Katherine Whalley
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Whalley, K. A depressing TRP. Nat Rev Neurosci 9, 324 (2008). https://doi.org/10.1038/nrn2376

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