title: TRPV4 activation at the physiological temperature is a critical determinant of neuronal excitability and behavior.
abstract: For homeothermic animals, constant body temperature is an important determinant of brain function. It is well established that changes in brain temperature dynamically influence hippocampal activity. We previously reported that the thermosensor TRPV4 (activated above 34 °C) is activated at the physiological temperature in hippocampal neurons and controls neuronal excitability in vitro. Here, we examined if TRPV4 regulates neuronal excitability through its activation at the physiological temperature in vivo. We found that TRPV4-deficient (TRPV4KO) mice exhibit reduced depression-like and social behaviors compared to wild-type (WT) mice, and the number of c-fos positive cells in the dentate gyrus was significantly reduced upon the depression-like behaviors. We measured resting membrane potentials (RMPs) in the hippocampal granule cells from slice preparations at 35 °C and found that TRPV4-positive neurons significantly depolarized the RMPs through TRPV4 activation at the physiological temperature. The depolarization increased the spike numbers depending on the enhancement of TRPV4 activation. We also found that theta-frequency electroencephalogram (EEG) activities in TRPV4KO mice during wake periods were significantly reduced compared with those in WT mice. Taken together, we report for the first time that TRPV4 activation at the physiological temperature is important to regulate neuronal excitability and behaviors in mammals.
authors.affiliation: Department of Molecular and Cellular Neurobiology, Gunma University Graduate School of Medicine, Maebashi, 371-8511, Japan. shibasaki@gunma-u.ac.jp.
authors.forename: Koji
authors.identifier: http://orcid.org/0000-0003-2330-1749
authors.initials: K
authors.lastname: Shibasaki
authors.affiliation: Department of Molecular and Cellular Neurobiology, Gunma University Graduate School of Medicine, Maebashi, 371-8511, Japan.
authors.forename: Shouta
authors.initials: S
authors.lastname: Sugio
authors.affiliation: Section of Behavior Patterns, Maebashi, Japan.|Japan Science and Technology Agency, Core Research for Evolutional Science and Technology (CREST), Tokyo, Japan.
authors.forename: Keizo
authors.initials: K
authors.lastname: Takao
authors.affiliation: Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya, 464-8601, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yamanaka
authors.affiliation: Section of Behavior Patterns, Maebashi, Japan.|Japan Science and Technology Agency, Core Research for Evolutional Science and Technology (CREST), Tokyo, Japan.|Division of Systems Medicine, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, 470-7792, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Miyakawa
authors.affiliation: Division of Cell Signaling, National Institute for Physiological Sciences, Okazaki, Japan.|Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, Okazaki, 444-8585, Japan.|Department of Physiological Sciences, The Graduate University for Advanced Studies, Okazaki, 444-8585, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Tominaga
authors.affiliation: Department of Molecular and Cellular Neurobiology, Gunma University Graduate School of Medicine, Maebashi, 371-8511, Japan.
authors.forename: Yasuki
authors.initials: Y
authors.lastname: Ishizaki
mesh_terms: D000200:Action Potentials; D000818:Animals; D001831:Body Temperature; D018891:Dentate Gyrus / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D051379:Mice; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D012919:Social Behavior; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*; D013826:Theta Rhythm
chemical_list: D050916:TRPV Cation Channels; C486576:Trpv4 protein, mouse
keywords: Behavior; Brain temperature; Neuron; Synapse; TRPV4