NEUROPEPTIDE-Y AND GLUTAMATE BLOCK EACH OTHERS PHASE-SHIFTS IN THE SUPRACHIASMATIC NUCLEUS IN-VITRO

The suprachiasmatic nuclei contain a circadian clock whose activity ca n be recorded in vitro for several days. Photic information is conveye d to the nuclei primarily via a direct projection from the retina, the retinohypothalamic tract, utilizing an excitatory amino acid neurotra nsmitter. Photic phase shifts may be mimicked by application of glutam ate in vitro. A second, indirect pathway to the suprachiasmatic nuclei via the geniculohypothalamic tract utilizes neuropeptide Y as a trans mitter. Phase shifts to neuropeptide Y in vitro are similar to those s een to non-photic stimuli in vivo. We have used the hypothalamic slice preparation to examine the interactions of photic and non-photic stim uli in the suprachiasmatic nuclei. Coronal hypothalamic slices contain ing the suprachiasmatic nuclei were prepared from Syrian hamsters and 3 min recordings of the firing rate of individual cells were performed throughout a 12 h period. Control slices receiving either no applicat ion or application of artificial cerebrospinal fluid to the suprachias matic nucleus showed a consistent daily peak in their rhythms. Glutama te produces phase shifts of the circadian clock in the hamster hypotha lamic slice preparation during the subjective night but not during the subjective day. These phase shifts were similar in timing and directi on to the photic phase response curve in vivo confirming previous work with the rat slice preparation. Neuropeptide Y produces phase shifts of the circadian clock during the subjective day but not during the su bjective night. The phase shifts are similar in timing and direction t o the non-photic phase response curve in vivo, confirming previous in vitro work. We then examined the interaction of these neurochemicals w ith each other at various limes during the circadian cycle. We found t hat both advances and delays to glutamate in the slice are blocked by application of neuropeptide Y. We also found that phase shifts to neur opeptide Y in the slice are blocked by application of glutamate. These results indicate that photic and non-photic associated neurochemicals can block each others phase shifting effects within the suprachiasmat ic nucleus in vitro. These experiments demonstrate the ability of phot ic and non-photic associated neurochemicals to interact at the level o f the suprachiasmatic nucleus. It is clear that neuropeptide Y antagon izes the effect of glutamate during the subjective night, and that glu tamate antagonizes the effect of neuropeptide Y during the subjective day. Great care must be taken when devising treatments where photic an d non-photic signals may interact. (C) 1997 IBRO. Published by Elsevie r Science Ltd.