THE ROLE OF GLUTAMATE IN THE PHOTIC REGULATION OF THE SUPRACHIASMATICNUCLEUS

Endogenous circadian rhythms govern most aspects of physiology and beh aviour in mammals, including body temperature, autonomic and endocrine function, and sleep-wake cycles. Such rhythms are generated by the su prachiasmatic nucleus of the hypothalamus (SCN), but are synchronised to the environmental light-dark cycle by photic cues perceived by the retina and conveyed to the SCN via the retinohypothalamic tract (RHT). This review considers many lines of evidence from diverse experimenta l approaches indicating that the RHT employs glutamate (or a related e xcitatory amino acid) as a neurotransmitter. Ultrastructural studies d emonstrate the presence of glutamate in presynaptic terminals within t he SCN. In situ hybridisation and immunocytochemical studies reveal th e presence of several NMDA (NMDAR1, NMDAR2C), non-NMDA (GluR1, GluR2, GluR4) and metabotropic (mGluR1) glutamate receptor subunits in the SC N. Messenger RNA encoding a glutamate transporter protein is also pres ent. In behavioural tests, glutamate antagonists can block the effects of light in phase-shifting circadian rhythms. Such treatments also bl ock the induction of c-fos within SCN cells by light, whereas a glutam ate agonist (NMDA) induces c-fos expression. In hypothalamic slice pre parations in vitro, electrical stimulation of the optic nerves induces release of glutamate and aspartate, and glutamate antagonists block f ield potentials in the SCN evoked by stimulation of the optic nerve. C ircadian rhythms of electrical activity which persist in vitro are pha se shifted by application of glutamate in a manner which mimics the ph ase shifting effects of light in vivo. This wide range of experimental findings provides strong support for the hypothesis that glutamate is the principal neurotransmitter within the RHT, and thus conveys photi c cues to the circadian timing system in the SCN. Copyright (C) 1996 E lsevier Science Ltd.