INVOLVEMENT OF VASOACTIVE INTESTINAL POLYPEPTIDE IN NMDA-INDUCED PHASE DELAY OF FIRING ACTIVITY RHYTHM IN THE SUPRACHIASMATIC NUCLEUS IN-VITRO

Glutamate has been reported to be involved in the transmission of phot ic information from the retina to the suprachiasmatic nucleus (SCN). T herefore, we investigated whether the application of N-methyl-D-aspart ate (NMDA), a glutamate receptor agonist could, reset the circadian rh ythm of SCN firing activity in vitro. Treatment with NMDA for 1 h betw een projected zeitgeber time (ZT) 13-14 produced a phase delay in a co ncentration-dependent manner. The NMDA-induced phase delay was antagon ized by an NMDA-receptor antagonist, MK-801 (100 mu M). The retinohypo thalamic tract has been reported to make terminals on neurons possessi ng vasoactive intestinal polypeptide (VIP). Therefore, we investigated the effects of NMDA on VIP release from the SCN and on VIP immunoreac tivity in the SCN. Application of NMDA for 15 min between ZT 13-15 inc reased release of VIP from the SCN. In contrast to release, the conten t of VIP in the SCN tissue was reduced by application of NMDA. Immunoh istochemical analysis revealed that application of NMDA for 4 h or 1 h reduced VIP immunoreactivity in the SCN. To investigate the possibili ty that VIP released by NMDA could reset SCN neuronal activity, we exa mined the effects of VIP on the SCN neuronal activity rhythm. Cotreatm ent with VIP (1 mu M) and gastrin-releasing peptide (1 mu M) for I h b etween ZT 13-14 caused a phase-delay of SCN activity rhythm. These fin dings suggest that activation of NMDA receptors during early subjectiv e night causes a phase delay of the SCN neuronal activity via facilita tion of VIP release in this nucleus.