Neuropeptide Y and N-methyl-D-aspartic acid interact within the suprachiasiviatic nuclei to alter circadian phase

Circadian rhythms are reset by exposure to photic stimuli and nonphotic stimuli. Glutamate appears to be the primary neurotransmitter that communicates photic stimuli to the circadian clock located in the suprachiasmatic nucleus. There is also substantial evidence that neuropeptide Y (NPY) mediates the effects of at least some nonphotic stimuli on the circadian clock. The purpose of this study was to investigate how NPY and glutamate receptor activation interact to reset the phase of the circadian clock. Microinjection of the glutamate agonist N-methyl-D-aspartic acid (NMDA) during the subjective day significantly decreased NPY-induced phase advances. During the late subjective night, NMDA induced light-like phase advances, which were significantly reduced by microinjection of NPY. Microinjection of NPY inhibited NMDA-induced phase advances during the late subjective night, even when sodium-dependent action potentials were inhibited by tetrodotoxin. These data support the hypothesis that, during the subjective night, NPY and NMDA act on the same clock cells or on cells that communicate with clock cells by mechanisms not requiring action potentials. Although NPY and NMDA appear to be mutually inhibitory during both the day and the night, the mechanisms of this inhibition appear to be different during the day versus the night. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved.