title: Compartment-specific modulation of GABAergic synaptic transmission by TRPV1 channels in the dentate gyrus.
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.
authors.affiliation: 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.
authors.forename: Andrés E
authors.identifier: http://orcid.org/0000-0001-8795-9238
authors.initials: AE
authors.lastname: Chávez
authors.affiliation: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611.
authors.forename: Vivian M
authors.initials: VM
authors.lastname: Hernández
authors.affiliation: Dominick P. Purpura, Department of Neuroscience, Albert Einstein College of Medicine, Kennedy Center, Bronx, New York 10461 and.
authors.forename: Alma
authors.identifier: http://orcid.org/0000-0001-9942-8039
authors.initials: A
authors.lastname: Rodenas-Ruano
authors.affiliation: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611.
authors.forename: C Savio
authors.initials: CS
authors.lastname: Chan
authors.affiliation: 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.
authors.forename: Pablo E
authors.initials: PE
authors.lastname: Castillo
mesh_terms: D000818:Animals; D018891:Dentate Gyrus / Q000502:physiology*; D005260:Female; D059330:GABAergic Neurons / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000502:physiology*; D050916:TRPV Cation Channels / Q000502:physiology*
chemical_list: D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse
keywords: GABA; cannabinoid; endocytosis; feedforward inhibition; hippocampus; interneuron