TRPV1 regulates excitatory innervation of OLM neurons in the hippocampus

Joaquin I. Hurtado-Zavala; Binu Ramachandran; Saheeb Ahmed; Rashi Halder; Christiane Bolleyer; Ankit Awasthi; Markus A. Stahlberg; Robin J. Wagener; Kristin Anderson; Ryan M. Drenan; Henry A. Lester; Julie M. Miwa; Jochen F. Staiger; Andre Fischer; Camin Dean

doi:10.1038/ncomms15878

TRPV1 regulates excitatory innervation of OLM neurons in the hippocampus

Joaquin I. Hurtado-Zavala, Binu Ramachandran, Saheeb Ahmed, Rashi Halder, Christiane Bolleyer, Ankit Awasthi, Markus A. Stahlberg, Robin J. Wagener, Kristin Anderson, Ryan M. Drenan, Henry A. Lester, Julie M. Miwa, Jochen F. Staiger, Andre Fischer, Camin Dean^*

^*Corresponding author for this work

Pharmacology

Research output: Contribution to journal › Article › peer-review

39 Scopus citations

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.

Original language	English (US)
Article number	15878
Journal	Nature communications
Volume	8
DOIs	https://doi.org/10.1038/ncomms15878
State	Published - Jul 19 2017

Funding

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.

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Hurtado-Zavala, J. I., Ramachandran, B., Ahmed, S., Halder, R., Bolleyer, C., Awasthi, A., Stahlberg, M. A., Wagener, R. J., Anderson, K., Drenan, R. M., Lester, H. A., Miwa, J. M., Staiger, J. F., Fischer, A., & Dean, C. (2017). TRPV1 regulates excitatory innervation of OLM neurons in the hippocampus. Nature communications, 8, Article 15878. https://doi.org/10.1038/ncomms15878

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title = "TRPV1 regulates excitatory innervation of OLM neurons in the hippocampus",

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.",

author = "Hurtado-Zavala, {Joaquin I.} and Binu Ramachandran and Saheeb Ahmed and Rashi Halder and Christiane Bolleyer and Ankit Awasthi and Stahlberg, {Markus A.} and Wagener, {Robin J.} and Kristin Anderson and Drenan, {Ryan M.} and Lester, {Henry A.} and Miwa, {Julie M.} and Staiger, {Jochen F.} and Andre Fischer and Camin Dean",

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AU - Hurtado-Zavala, Joaquin I.

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AU - Ahmed, Saheeb

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AU - Bolleyer, Christiane

AU - Awasthi, Ankit

AU - Stahlberg, Markus A.

AU - Wagener, Robin J.

AU - Anderson, Kristin

AU - Drenan, Ryan M.

AU - Lester, Henry A.

AU - Miwa, Julie M.

AU - Staiger, Jochen F.

AU - Fischer, Andre

AU - Dean, Camin

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N2 - 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.

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TRPV1 regulates excitatory innervation of OLM neurons in the hippocampus

Abstract

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