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

Andrés E. Chávez, Vivian M. Hernández, Alma Rodenas-Ruano, C. Savio Chan, Pablo E. Castillo

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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-dependentinternalization of GABA receptors. Altogether, these findings reveal a novel form of compartment-specific regulation whereby TRPV1 channels can modify synaptic function in the brain.

Original languageEnglish (US)
Pages (from-to)16621-16629
Number of pages9
JournalJournal of Neuroscience
Volume34
Issue number50
DOIs
StatePublished - Dec 10 2014

Fingerprint

Dentate Gyrus
Synaptic Transmission
Brain
Ligand-Gated Ion Channels
TRPV Cation Channels
Endocannabinoids
Clathrin
GABA Receptors
Nociception
Calcineurin
Electrophysiology
Capsaicin
Sensory Receptor Cells
Knockout Mice
Synapses
gamma-Aminobutyric Acid
Pharmacology
Depression

Keywords

  • Cannabinoid
  • Endocytosis
  • Feedforward inhibition
  • GABA
  • Hippocampus
  • Interneuron

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Compartment-specific modulation of GABAergic synaptic transmission by TRPV1 channels in the dentate gyrus. / Chávez, Andrés E.; Hernández, Vivian M.; Rodenas-Ruano, Alma; Savio Chan, C.; Castillo, Pablo E.

In: Journal of Neuroscience, Vol. 34, No. 50, 10.12.2014, p. 16621-16629.

Research output: Contribution to journalArticle

Chávez, Andrés E. ; Hernández, Vivian M. ; Rodenas-Ruano, Alma ; Savio Chan, C. ; Castillo, Pablo E. / Compartment-specific modulation of GABAergic synaptic transmission by TRPV1 channels in the dentate gyrus. In: Journal of Neuroscience. 2014 ; Vol. 34, No. 50. pp. 16621-16629.
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