Compartment-specific modulation of GABAergic synaptic transmission by TRPV1 channels in the dentate gyrus

The transient receptor potential TRPV1 or vanilloid receptor is a nonselective ligand-gated channel highly expressed in primary sensory neurons where it mediates nociception. TRPV1 is also expressed in the brain where its activation depresses excitatory synaptic transmission. Whether TRPV1 also regu...

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Published inThe Journal of neuroscience Vol. 34; no. 50; pp. 16621 - 16629
Main Authors Chávez, Andrés E, Hernández, Vivian M, Rodenas-Ruano, Alma, Chan, C Savio, Castillo, Pablo E
Format Journal Article
LanguageEnglish
Published United States Society for Neuroscience 10.12.2014
Subjects
Animals
Dentate Gyrus - physiology
Female
GABAergic Neurons - physiology
Hippocampus - physiology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Organ Culture Techniques
Rats
Rats, Sprague-Dawley
Rats, Wistar
Synaptic Transmission - physiology
TRPV Cation Channels - physiology
GABA
endocytosis
interneuron
feedforward inhibition
hippocampus
cannabinoid
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Summary:The transient receptor potential TRPV1 or vanilloid receptor is a nonselective ligand-gated channel highly expressed in primary sensory neurons where it mediates nociception. TRPV1 is also expressed in the brain where its activation depresses excitatory synaptic transmission. Whether TRPV1 also regulates inhibitory synapses in the brain is unclear. Here, using a combination of pharmacology, electrophysiology, and an in vivo knockdown strategy, we report that TRPV1 activation by capsaicin or by the endocannabinoid anandamide depresses somatic, but not dendritic inhibitory transmission in both rat and mouse dentate gyrus. The effect on somatic inhibition was absent in TRPV1 knock-out mice and was also eliminated by two different TRPV1 shRNAs expressed in dentate granule cells, strongly supporting a functional role for TRPV1 in modulating GABAergic synaptic function. Moreover, TRPV1-mediated depression occurs independently of GABA release, requires postsynaptic Ca(2+) rise and activation of calcineurin, and is likely due to clathrin-dependent internalization of GABA receptors. Altogether, these findings reveal a novel form of compartment-specific regulation whereby TRPV1 channels can modify synaptic function in the brain.
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Author contributions: A.E.C. and P.E.C. designed research; A.E.C. and A.R.-R. performed research; V.M.H. and C.S.C. designed and generated all shRNA vectors; A.E.C. and A.R.-R. analyzed data; A.E.C. and P.E.C. wrote the paper.
ISSN:0270-6474
1529-2401
DOI:10.1523/jneurosci.3635-14.2014