Format

Send to

Choose Destination
J Neurosci. 2014 Dec 10;34(50):16621-9. doi: 10.1523/JNEUROSCI.3635-14.2014.

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

Author information

1
Dominick P. Purpura, Department of Neuroscience, Albert Einstein College of Medicine, Kennedy Center, Bronx, New York 10461 and andres.chavez@einstein.yu.edu pablo.castillo@einstein.yu.edu.
2
Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611.
3
Dominick P. Purpura, Department of Neuroscience, Albert Einstein College of Medicine, Kennedy Center, Bronx, New York 10461 and.

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-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.

KEYWORDS:

GABA; cannabinoid; endocytosis; feedforward inhibition; hippocampus; interneuron

PMID:
25505315
PMCID:
PMC4261091
DOI:
10.1523/JNEUROSCI.3635-14.2014
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center