Neuropeptide Y attenuates NMDA-induced phase shifts in the SCN of NPY Y1 receptor knockout mice in vitro.

Neuropeptide Y (NPY) blocks the effect of light on the mammalian circadian clock during the subjective night. The present study explores the role of the NPY Y1 receptor in this interaction. The effect of NPY when co-applied with NMDA, a glutamate agonist that can mimic the effect of light, was examined in NPY Y1-/- mice (background strain 129SVXBalb/c) using electrophysiology. Cells in the suprachiasmatic nucleus (SCN), the master circadian pacemaker, show a circadian rhythm in spontaneous firing rate that can be recorded in vitro. The results demonstrated that NPY attenuated the phase shifts to NMDA in both the Y1-/- mice and control mice, indicating that the Y1 receptor does not mediate the NPY blockade of photic-like phase shifts. The peak in frequency in the untreated control brain slices from Y1-/- mice was advanced by approximately 1 h as compared to the Y1+/+ mice. The Y1 receptor may contribute to a functional model of circadian rhythms, but apparently is not essential for the effects of NPY on photic phase shifts.