Capsaicin-induced changes in LTP in the lateral amygdala are mediated by TRPV1.

Carsten Zschenderlein,Oliver Von Bohlen Und Halbach,Doris Albrecht,Christine Gebhardt,Christoph Kulisch

doi:10.1371/journal.pone.0016116

Carsten Zschenderlein, Oliver Von Bohlen Und Halbach + Show 3 more

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https://doi.org/10.1371/journal.pone.0016116

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Abstract

The transient receptor potential vanilloid type 1 (TRPV1) channel is a well recognized polymodal signal detector that is activated by painful stimuli such as capsaicin. Here, we show that TRPV1 is expressed in the lateral nucleus of the amygdala (LA). Despite the fact that the central amygdala displays the highest neuronal density, the highest density of TRPV1 labeled neurons was found within the nuclei of the basolateral complex of the amygdala. Capsaicin specifically changed the magnitude of long-term potentiation (LTP) in the LA in brain slices of mice depending on the anesthetic (ether, isoflurane) used before euthanasia. After ether anesthesia, capsaicin had a suppressive effect on LA-LTP both in patch clamp and in extracellular recordings. The capsaicin-induced reduction of LTP was completely blocked by the nitric oxide synthase (NOS) inhibitor L-NAME and was absent in neuronal NOS as well as in TRPV1 deficient mice. The specific antagonist of cannabinoid receptor type 1 (CB1), AM 251, was also able to reduce the inhibitory effect of capsaicin on LA-LTP, suggesting that stimulation of TRPV1 provokes the generation of anandamide in the brain which seems to inhibit NO synthesis. After isoflurane anesthesia before euthanasia capsaicin caused a TRPV1-mediated increase in the magnitude of LA-LTP. Therefore, our results also indicate that the appropriate choice of the anesthetics used is an important consideration when brain plasticity and the action of endovanilloids will be evaluated. In summary, our results demonstrate that TRPV1 may be involved in the amygdala control of learning mechanisms.

Highlights

The transient receptor potential vanilloid type 1 (TRPV1) channel is a nonselective cation channel with high Ca2+ permeability that belongs to the TRP family of proteins [1]
The functional role of TRPV1 receptors located in the LA is not clear, since these cells are unlikely to be exposed to capsaicin or noxious heat directly
Our results further show that capsaicin-induced suppression of high frequency stimulation (HFS)-induced LA-long-term potentiation (LTP) is mediated by the stimulation of TRPV1 receptors, since capsazepine and AMG9810 blocked the capsaicin-induced effect and the effect was absent in TRPV1 deficient mice

Summary

Introduction

The transient receptor potential vanilloid type 1 (TRPV1) channel is a nonselective cation channel with high Ca2+ permeability that belongs to the TRP family of proteins [1]. EC stimulation activates excitatory afferences from cortical structures and includes afferences from the lateral entorhinal and perirhinal cortex that course through the EC and synapse in the lateral and the basolateral nucleus of the amygdala [16]. Studies performed in coronal brain slices have shown that high frequency stimulation (HFS) [26] is able to induced persistent LA-LTP only if the postsynaptic cells were depolarized [14] or GABA receptor antagonists were applied [27,28]. LA-LTP in horizontal brain slices can be induced either by HFS of ECafferents [29,30] or of intranuclear fibers (IN-stimulation) [30,31] without inhibiting GABA receptors. We could induce stable LA-LTP by stimulation of intranuclear afferents in recordings with sharp microelectrodes [34] without adding GABA receptor antagonists and without additional depolarization of the postsynaptic cell

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