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 photic information from the retina to the suprachiasmatic nucleus (SCN). Therefore, we investigated whether the application of N-methyl-d-aspartate (NMDA), a glutamate receptor agonist could, reset the circadian rhythm of SCN firing activity in vitro. Treatment with NMDA for 1 h between projected zeitgeber time (ZT) 13-14 produced a phase delay in a concentration-dependent manner. The NMDA-induced phase delay was antagonized by an NMDA-receptor antagonist, MK-801 (100 μM). The retinohypothalamic tract has been reported to make terminals on neurons possessing vasoactive intestinal polypeptide (VIP). Therefore, we investigated the effects of NMDA on VIP release from the SCN and on VIP immunoreactivity in the SCN. Application of NMDA for 15 min between ZT 13-15 increased release of VIP from the SCN. In contrast to release, the content of VIP in the SCN tissue was reduced by application of NMDA. Immunohistochemical analysis revealed that application of NMDA for 4 h or 1 h reduced VIP immunoreactivity in the SCN. To investigate the possibility that VIP released by NMDA could reset SCN neuronal activity, we examined the effects of VIP on the SCN neuronal activity rhythm. Cotreatment with VIP (1 μM) and gastrin-releasing peptide (1 μM) for 1 h between ZT 13-14 caused a phase-delay of SCN activity rhythm. These findings suggest that activation of NMDA receptors during early subjective night causes a phase delay of the SCN neuronal activity via facilitation of VIP release in this nucleus.