RESETTING THE BIOLOGICAL CLOCK - MEDIATION OF NOCTURNAL CIRCADIAN SHIFTS BY GLUTAMATE AND NO

Circadian rhythms of mammals are timed by an endogenous clock with a p eriod of about 24 hours located in the suprachiasmatic nucleus (SCN) o f the hypothalamus. Light synchronizes this clock to the external envi ronment by daily adjustments in the phase of the circadian oscillation . The mechanism has been thought to involve the release of excitatory amino acids from retinal afferents to the SCN. Brief treatment of rat SCN in vitro with glutamate (Glu), N-methyl-D-aspartate (NMDA), or nit ric oxide (NO) generators produced lightlike phase shifts of circadian rhythms. The SCN exhibited calcium-dependent nitric oxide synthase (N OS) activity. Antagonists of NMDA or NOS pathways blocked Glu effects in vitro, and intracerebroventricular injection of a NOS inhibitor in vivo blocked the light-induced resetting of behavioral rhythms. Togeth er, these data indicate that Glu release, NMDA receptor activation, NO S stimulation, and NO production link light activation of the retina t o cellular changes within the SCN mediating the phase resetting of the biological clock.