Okazaki Institute for Integrative Biology

RESEARCH THEMES

We mainly investigate molecular mechanisms of thermosensation, nociception and taste sensation by focusing on TRP ion channels (Figure). We also investigate neurons in hypothalamus which are involved in the maintenance of homeostasis.

The followings are major projects in progress.
(1) Molecular mechanisms of thermosensation: Temperature sensing ability is conferred by ion channels of the TRPV, TRPM and TRPA families. We try to clarify the molecular mechanisms of thermosensation and their physiological significance by focusing on those thermosensitive TRP channels. We are also doing behavioral analyses of mice lacking TRPV3, TRPV4 or TRPM2. Furthermore, we are trying to isolate a novel thermosensitive TRP channels.

(2) Molecular mechanisms of nociception: Capsaicin receptor TRPV1 and TRPA1 are ion channels activated by different noxious stimuli. We try to clarify the nociceptive mechanisms at peripheral nerve endings by focusing on TRP ion channels, especially TRPV1 and TRPA1. We are also doing behavioral analyses of TRPV1- or TRPA1-deficient mice.

(3) We study neurons in the hypothalamus. The hypothalamus is implicated in the maintenance of homeostasis, such as body temperature regulation, feeding regulation and sleep/wakefulness regulation. We make transgenic animals and analyze them by using many techniques including electrophysiological analysis such as slice patch clamp and in vivo extracellular recording as well as immunohistochemical analysis and behavioral analysis such as sleep recording. We try to reveal the neural mechanism, which involved in the maintenance of homeostasis, in molecular, cellular and whole animal level.

SELECTED PUBLICATIONS

1. "Intracellular alkalization causes pain sensation through activation of TRPA1." . Clin. Invest., 118, 4049-4057 2008
2. "Off-response property of an acid-activated cation channel complex PKD1L3/PKD2L1." EMBO R. 9, 690-697 2008
3. "Vasopressin increases locomotion through a V1a receptor in the orexin/hypocretin neurons- implication for water homeostasis." J. Neurosci., 28, 228-238 2008
4. "Effects of body temperature on neural activity in the hippocampus: regulation of resting membrane potentials by TRPV4." J. Neurosci., 27, 1566-1575 2007
5. "TRPM2 activation by cyclic ADP-ribose at body temperature is involved in insulin secretion." EMBO J., 25, 1804-1815 2006