Pflügers Archiv - European Journal of Physiology

, Volume 467, Issue 12, pp 2495–2507 | Cite as

TRPV4 activation at the physiological temperature is a critical determinant of neuronal excitability and behavior

  • Koji Shibasaki
  • Shouta Sugio
  • Keizo Takao
  • Akihiro Yamanaka
  • Tsuyoshi Miyakawa
  • Makoto Tominaga
  • Yasuki Ishizaki
Ion channels, receptors and transporters

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.

Keywords

TRPV4 Brain temperature Synapse Neuron Behavior 

Supplementary material

424_2015_1726_Fig9_ESM.gif (419 kb)
Supplementary Figure 1

Detection of c-fos mRNA by in situ hybridization. Scale Bar; 500 μm. (GIF 419 kb)

424_2015_1726_MOESM1_ESM.tif (1.6 mb)
(TIFF 1598 kb)
424_2015_1726_Fig10_ESM.gif (298 kb)
Supplementary Figure 2

Adult neurogenesis is normal in DG of TRPV4KO a, b; Adult neurogenesis was examined in WT or TRPV4KO DGs by incorporation and detection of BrdU (A), or detection of DCX (B). Scale Bars; 200 μm. c, d; Quantification of BrdU+ (C) or DCX+ (D) cell numbers in DG sections (3 independent animals, n = 16 slide glasses). (GIF 298 kb)

424_2015_1726_MOESM2_ESM.tif (1.1 mb)
(TIFF 1171 kb)

References

  1. 1.
    Alessandri-Haber N, Yeh JJ, Boyd AE, Parada CA, Chen X, Reichiling DB, Levine JD (2003) Hypotonicity induces TRPV4-mediated nociception in rat. Neuron 39:497–511CrossRefPubMedGoogle Scholar
  2. 2.
    Anderson P, Moser EI (1995) Brain temperature and hippocampal function. Hippocampus 5:491–498CrossRefGoogle Scholar
  3. 3.
    Auer-Grumbach M, Olschewski A, Papic L, Kremer H, McEntagart ME, Uhrig S, Fischer C, Frohlich E, Balint Z, Tang B, Strohmaier H, Lochmuller H, Schlotter-Weigel B, Senderek J, Krebs A, Dick KJ, Petty R, Longman C, Anderson NE, Padberg GW, Schelhaas HJ, van Ravenswaaij-Arts CMA, Pieber TR, Crosby AH, Guelly C (2010) Alterations in the ankyrin domain of TRPV4 cause congenital distal SMA, scapuloperoneal SMA and HMSN2C. Nat Genet 42:160–U196. doi:10.1038/Ng.508 PubMedCentralCrossRefPubMedGoogle Scholar
  4. 4.
    de la Pena E, Malkia A, Cabedo H, Belmonte C, Viana F (2005) The contribution of TRPM8 channels to cold sensing in mammalian neurones. J Physiol 567:415–426PubMedCentralCrossRefPubMedGoogle Scholar
  5. 5.
    Delany NS, Hurle M, Facer P, Alnadaf T, Plumpton C, Kinghorn I, See CG, Costigan M, Anand P, Woolf CJ, Crowther D, Sanseau P, Tate SN (2001) Identification and characterization of a novel human vanilloid receptor-like protein, VRL-2. Physiol Genomics 4:165–174PubMedGoogle Scholar
  6. 6.
    Fay T, Smith GW (1941) Observations on reflex responses during prolonged periods of human refrigeration. Arch Neurol Psychiat 45:215–222CrossRefGoogle Scholar
  7. 7.
    Fuster JM, Bauer RH (1974) Visual short-term memory deficit from hypothermia of frontal cortex. Brain Res 81:393–400CrossRefPubMedGoogle Scholar
  8. 8.
    Gasparini S, Saviane C, Voronin LL, Cherubini E (2000) Silent synapses in the developing hippocampus: lack of functional AMPA receptors or low probability of glutamate release? Proc Natl Acad Sci U S A 97:9741–9746PubMedCentralCrossRefPubMedGoogle Scholar
  9. 9.
    Groc L, Gustafsson B, Hanse E (2002) Spontaneous unitary synaptic activity in CA1 pyramidal neurons during early postnatal development: constant contribution of AMPA and NMDA receptors. J Neurosci 22:5552–5562PubMedGoogle Scholar
  10. 10.
    Grynkiewicz G, Poenie M, Tsien RY (1985) A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem 260:3440–3450PubMedGoogle Scholar
  11. 11.
    Guler AD, Lee H, Iida T, Shimizu I, Tominaga M, Caterina M (2002) Heat-evoked activation of the ion channel, TRPV4. J Neurosci 22:6408–6414PubMedGoogle Scholar
  12. 12.
    Hodgkin AI, Katz B (1949) The effect of temperature on the electrical activity of the giant axon of the squid. J Physiol 109:240–249PubMedCentralCrossRefPubMedGoogle Scholar
  13. 13.
    Kang SS, Shin SH, Auh CK, Chun J (2012) Human skeletal dysplasia caused by a constitutive activated transient receptor potential vanilloid 4 (TRPV4) cation channel mutation. Exp Mol Med 44:707–722. doi:10.3858/emm.2012.44.12.080 PubMedCentralCrossRefPubMedGoogle Scholar
  14. 14.
    Karlsson KA, Blumberg MS (2004) Temperature-induced reciprocal activation of hippocampal field activity. J Neurophysiol 91:583–588CrossRefPubMedGoogle Scholar
  15. 15.
    Komada M, Takao K, Miyakawa T (2008) Elevated plus maze for mice. J Vis Exp. doi:10.3791/1088 PubMedCentralPubMedGoogle Scholar
  16. 16.
    Kortner G, Schildhauer K, Petrova O, Schmidt I (1993) Rapid changes in metabolic cold defense and GDP binding to brown adipose tissue mitochondria of rat pups. Am J Physiol 264:R1017–1023PubMedGoogle Scholar
  17. 17.
    Landoure G, Zdebik AA, Martinez TL, Burnett BG, Stanescu HC, Inada H, Shi YJ, Taye AA, Kong LL, Munns CH, Choo SS, Phelps CB, Paudel R, Houlden H, Ludlow CL, Caterina MJ, Gaudet R, Kleta R, Fischbeck KH, Sumner CJ (2010) Mutations in TRPV4 cause Charcot-Marie-Tooth disease type 2C. Nat Genet 42:170–U109. doi:10.1038/Ng.512 PubMedCentralCrossRefPubMedGoogle Scholar
  18. 18.
    Liedtke W, Choe Y, Marti-Renom MA, Bell AM, Denis CS, Sali A, Hudspeth AJ, Friedman JM, Heller S (2000) Vanilloid receptor-related osmotically activated channel (VR-OAC), a candidate vertibrate osmoreceptor. Cell 103:525–535PubMedCentralCrossRefPubMedGoogle Scholar
  19. 19.
    Liedtke W, Friedman JM (2003) Abnormal osmotic regulation in trpv4−/− mice. Proc Natl Acad Sci U S A 100:13698–13703PubMedCentralCrossRefPubMedGoogle Scholar
  20. 20.
    Miyakawa T, Leiter LM, Gerber DJ, Gainetdinov RR, Sotnikova TD, Zeng H, Caron MG, Tonegawa S (2003) Conditional calcineurin knockout mice exhibit multiple abnormal behaviors related to schizophrenia. Proc Natl Acad Sci U S A 100:8987–8992. doi:10.1073/pnas.1432926100 PubMedCentralCrossRefPubMedGoogle Scholar
  21. 21.
    Mizuno A, Matsumoto N, Imai M, Suzuki M (2003) Impaired osmotic sensation in mice lacking TRPV4. Am J Physiolol Cell Physiol 285:C96–C101CrossRefGoogle Scholar
  22. 22.
    Mizuno H, Suzuki Y, Watanabe M, Sokabe T, Yamamoto T, Hattori R, Gotoh M, Tominaga M (2014) Potential role of transient receptor potential (TRP) channels in bladder cancer cells. J Physiol Sci 64:305–314. doi:10.1007/s12576-014-0319-6 CrossRefPubMedGoogle Scholar
  23. 23.
    Moser E, Mathiesen I, Andersen P (1993) Association between brain temperature and dentate field potentials in exploring and swimming rats. Science 259:1324–1326CrossRefPubMedGoogle Scholar
  24. 24.
    Moser EI, Andersen P (1994) Conserved spatial learning in cooled rats in spite of slowing of dentate field potentials. J Neurosci 14:4458–4466PubMedGoogle Scholar
  25. 25.
    Mutai H, Heller S (2003) Vertebrate and invertibrate TRPV-like mechanoreceptor. Cell Calcium 33:471–478CrossRefPubMedGoogle Scholar
  26. 26.
    Nilius B, Prenen J, Wissenbach U, Bodding M, Droogmans G (2001) Differential activation of the volume-sensitive cation channel TRP12 (OTRPC4) and volume-regulated anion currents in HEK-293 cells. Pflugers Arch 443:227–233CrossRefPubMedGoogle Scholar
  27. 27.
    Nillius B, Vriens J, Prenen J, Droogmans G, Voets T (2004) TRPV4 calcium entry channel: a paradigm for gating diversity. Am J Physiolol Cell Physiol 286:C195–C205CrossRefGoogle Scholar
  28. 28.
    Ritchie JM, Straub RW (1956) The effect of cooling on the size of the action potential of mammalian non-medullated fibers. J Physiol 134:712–717PubMedCentralCrossRefPubMedGoogle Scholar
  29. 29.
    Schiff SJ, Somjen GG (1985) The effects of temperature on synaptic transmission in hippocampal tissue slices. Brain Res 345:279–284CrossRefPubMedGoogle Scholar
  30. 30.
    Shibasaki K, Ishizaki Y, Mandadi S (2013) Astrocytes express functional TRPV2 ion channels. Biochem Biophys Res Commun 441:327–332. doi:10.1016/j.bbrc.2013.10.046 CrossRefPubMedGoogle Scholar
  31. 31.
    Shibasaki K, Nakahira K, Trimmer JS, Shibata R, Akita M, Watanabe S, Ikenaka K (2004) Mossy fibre contact triggers the targeting of Kv4.2 potassium channels to dendrites and synapses in developing cerebellar granule neurons. J Neurochem 89:897–907CrossRefPubMedGoogle Scholar
  32. 32.
    Shibasaki K, Suzuki M, Mizuno A, Tominaga M (2007) Effects of body temperature on neural activity in the hippocampus: regulation of resting membrane potentials by transient receptor potential vanilloid 4. J Neuroscience :Off J Soc Neuroscience 27:1566–1575. doi:10.1523/JNEUROSCI.4284-06.2007 CrossRefGoogle Scholar
  33. 33.
    Shibasaki K, Takebayashi H, Ikenaka K, Feng L, Gan L (2007) Expression of the basic helix-loop-factor Olig2 in the developing retina: Olig2 as a new marker for retinal progenitors and late-born cells. Gene Expr Patterns 7:57–65CrossRefPubMedGoogle Scholar
  34. 34.
    Shibasaki K, Tominaga M, Ishizaki Y (2015) Hippocampal neuronal maturation triggers post-synaptic clustering of brain temperature-sensor TRPV4. Biochem Biophys Res Commun 458:168–173. doi:10.1016/j.bbrc.2015.01.087 CrossRefPubMedGoogle Scholar
  35. 35.
    Shuttleworth TJ, Thompson JL (1991) Effect of temperature on receptor-activated changes in [Ca2+]i and their determination using fluorescent probes. J Biol Chem 266:1410–1414PubMedGoogle Scholar
  36. 36.
    Stortmann R, Harteneck C, Nunnenmacher K, Schultz G, Plant TD (2000) OTRPC4, a nonselective cation channel that confers sensitivity to extracellular osmolarity. Nature Cell Biol 2:695–702CrossRefGoogle Scholar
  37. 37.
    Suzuki M, Mizuno A, Kodaira K, Imai M (2003) Impaired pressure sensation in mice lacking TRPV4. JBiol Chem 278:22664–22668CrossRefGoogle Scholar
  38. 38.
    Takao K, Miyakawa T (2006) Light/dark transition test for mice. J Vis Exp: 104. doi:10.3791/104
  39. 39.
    Taschenberger H, von Gersdorff H (2000) Fine-tuning an auditory synapse for speed and fidelity: developmental changes in presynaptic waveform, EPSC kinetics, and synaptic plasticity. J Neurosci 20:9162–9173PubMedGoogle Scholar
  40. 40.
    Thompson SM, Masukawa LM, Prince DA (1985) Temperature dependence of intrinsic membrane properties and synaptic potentials in hippocampal CA1 neurons in vitro. J Neurosci 5:817–824PubMedGoogle Scholar
  41. 41.
    Torgersen J, Strand K, Bjelland TW, Klepstad P, Kvale R, Soreide E, Wentzel-Larsen T, Flaatten H (2010) Cognitive dysfunction and health-related quality of life after a cardiac arrest and therapeutic hypothermia. Acta Anaesthesiol Scand 54:721–728. doi:10.1111/j.1399-6576.2010.02219.x CrossRefPubMedGoogle Scholar
  42. 42.
    Veruki ML, Morkve SH, Hartveit E (2003) Functional properties of spontaneous EPSCs and non-NMDA receptors in rod amacrine (AII) cells in the rat retina. J Physiol 549:759–774PubMedCentralCrossRefPubMedGoogle Scholar
  43. 43.
    Watanabe H, Davis JB, Smart D, Jerman JC, Smith GD, Hayes P, Vriens J, Cairns W, Wissenbach U, Prenen J, Flockerzi V, Droogmans G, Benham CD, Nillius B (2002) Activation of TRPV4 channels (hVRL-2/mTRP12) by phorbol derivatives. J Biol Chem 277:13569–13577CrossRefPubMedGoogle Scholar
  44. 44.
    Watanabe H, Vriens J, Prenen J, Droogmans G, Voets T, Nillius B (2003) Anandamide and arachidonic acid use epoxyeicosatrienoic acids to activate TRPV4 channels. Nature 424:434–438CrossRefPubMedGoogle Scholar
  45. 45.
    Watanabe H, Vriens J, Suh SH, Benham CD, Droogmans G, Nillius B (2002) Heat-evoked activation of TRPV4 channels in a HEK293 cell expression system and in native mouse aorta endothelial cells. J Biol Chem 277:47044–47051CrossRefPubMedGoogle Scholar
  46. 46.
    Wissenbach U, Bodding M, Freichel M, Flockerzi V (2000) Trp12, a novel Trp related protein from kidney. FEBS Letter 485:127–134CrossRefGoogle Scholar
  47. 47.
    Yuen RKC, Thiruvahindrapuram B, Merico D, Walker S, Tammimies K, Hoang N, Chrysler C, Nalpathamkalam T, Pellecchia G, Liu Y, Gazzellone MJ, D'Abate L, Deneault E, Howe JL, Liu RSC, Thompson A, Zarrei M, Uddin M, Marshall CR, Ring RH, Zwaigenbaum L, Ray PN, Weksberg R, Carter MT, Fernandez BA, Roberts W, Szatmari P, Scherer SW (2015) Whole-genome sequencing of quartet families with autism spectrum disorder. Nat Med 21:97–103. doi:10.1038/Nm.3792 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.Department of Molecular and Cellular NeurobiologyGunma University Graduate School of MedicineMaebashiJapan
  2. 2.Section of Behavior PatternsMaebashiJapan
  3. 3.Division of Cell Signaling, National Institute for Physiological SciencesOkazakiJapan
  4. 4.Okazaki Institute for Integrative BioscienceNational Institutes of Natural SciencesOkazakiJapan
  5. 5.Department of Physiological SciencesThe Graduate University for Advanced StudiesOkazakiJapan
  6. 6.Department of Neuroscience II, Research Institute of Environmental MedicineNagoya UniversityNagoyaJapan
  7. 7.Japan Science and Technology Agency, Core Research for Evolutional Science and Technology (CREST)TokyoJapan
  8. 8.Division of Systems Medicine, Institute for Comprehensive Medical ScienceFujita Health UniversityToyoakeJapan

Personalised recommendations