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TRPV1 regulates excitatory innervation of OLM neurons in the hippocampus

Hurtado-Zavala, Joaquin I. and Ramachandran, Binu and Ahmed, Saheeb and Halder, Rashi and Bolleyer, Christiane and Awasthi, Ankit and Stahlberg, Markus A. and Wagener, Robin J. and Anderson, Kristin and Drenan, Ryan M. and Lester, Henry A. and Miwa, Julie M. and Staiger, Jochen F. and Fischer, Andre and Dean, Camin (2017) TRPV1 regulates excitatory innervation of OLM neurons in the hippocampus. Nature Communications, 8 . Art. No. 15878. ISSN 2041-1723. PMCID PMC5524938. https://resolver.caltech.edu/CaltechAUTHORS:20170724-083914067

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Abstract

TRPV1 is an ion channel activated by heat and pungent agents including capsaicin, and has been extensively studied in nociception of sensory neurons. However, the location and function of TRPV1 in the hippocampus is debated. We found that TRPV1 is expressed in oriens-lacunosum-moleculare (OLM) interneurons in the hippocampus, and promotes excitatory innervation. TRPV1 knockout mice have reduced glutamatergic innervation of OLM neurons. When activated by capsaicin, TRPV1 recruits more glutamatergic, but not GABAergic, terminals to OLM neurons in vitro. When TRPV1 is blocked, glutamatergic input to OLM neurons is dramatically reduced. Heterologous expression of TRPV1 also increases excitatory innervation. Moreover, TRPV1 knockouts have reduced Schaffer collateral LTP, which is rescued by activating OLM neurons with nicotine—via α2β2-containing nicotinic receptors—to bypass innervation defects. Our results reveal a synaptogenic function of TRPV1 in a specific interneuron population in the hippocampus, where it is important for gating hippocampal plasticity.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1038/ncomms15878DOIArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/pmc5524938/PubMed CentralArticle
ORCID:
AuthorORCID
Drenan, Ryan M.0000-0002-8141-8577
Lester, Henry A.0000-0002-5470-5255
Additional Information:© 2017 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Received: 14 September 2016; Accepted: 09 May 2017; Published online: 19 July 2017. We thank Rory McQuiston, Julie Kauer, Manuela Schmidt, and Nils Brose for insightful discussions and critical review of the manuscript. This work was supported by NIH R44Da032464, R21DA033831, PA Cure 4100068719/Lehigh University Accelerator grants to J.M.M., and by a Sofja Kovalevskaja grant from the Alexander von Humboldt Foundation, European Research Council starting grant SytActivity FP7 260916, Deutsche Forschungsgemeinschaft grants CRC889, DE1951/1 and the Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), and the Boehringer Ingelheim Foundation, to C.D. Author Contributions: J.I.H.-Z. conceived the research, designed, performed and analysed experiments, and co-wrote the paper. B.R., S.A. and R.H., designed, performed and analysed experiments. C.B., performed experiments and analysed the data. R.J.W. and K.A. performed experiments. M.A.S. designed and optimized experiments. A.A. analysed experiments. R.M.D., H.A.L. and J.M.M. designed experiments, and contributed animal models. J.F.S. and A.F. supervised and funded the work. C.D. conceived the research, designed and analysed experiments, supervised and funded the work and co-wrote the paper. All authors discussed the results and commented on the manuscript. The authors declare no competing financial interests.
Funders:
Funding AgencyGrant Number
NIHR44Da032464
NIHR21DA033831
Lehigh UniversityPA Cure 4100068719
Alexander von Humboldt FoundationUNSPECIFIED
European Research Council (ERC)260916
Deutsche Forschungsgemeinschaft (DFG)CRC889
Deutsche Forschungsgemeinschaft (DFG)DE1951/1
Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB)UNSPECIFIED
Boehringer Ingelheim FoundationUNSPECIFIED
PubMed Central ID:PMC5524938
Record Number:CaltechAUTHORS:20170724-083914067
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20170724-083914067
Official Citation:Hurtado-Zavala, J. I. et al. TRPV1 regulates excitatory innervation of OLM neurons in the hippocampus. Nat. Commun. 8, 15878 doi: 10.1038/ncomms15878 (2017).
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:79286
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:24 Jul 2017 15:58
Last Modified:10 Apr 2020 18:51

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