Attenuation of circadian light induced phase advances and delays by neuropeptide Y and a neuropeptide Y Y1/Y5 receptor agonist

Circadian rhythms can be synchronised to photic and non-photic stimuli. The circadian clock, anatomically defined as the suprachiasmatic nucleus in mammals, can be phase shifted by light during the night. Non-photic stimuli reset the circadian rhythm during the day. Photic and non-photic stimuli have been shown to interact during the day and night. Precise mechanisms for these complex interactions are unknown. A possible pathway for non-photic resetting of the clock is thought to generate from the intergeniculate leaflet, which conveys information to the suprachiasmatic nucleus (SCN) through the geniculohypothalamic tract and utilises neuropeptide Y (NPY) as its primary neurotransmitter. Interactions between light and NPY were investigated during the early (2 h after activity onset) and late (6 h after activity onset) night in male Syrian hamsters. NPY microinjections into the region of the SCN significantly attenuated light-induced phase delay, during the early subjective night. Phase advances to light were completely inhibited by the administration of NPY during the late night. The precise mechanism by which NPY attenuates or blocks photic phase shifts is unclear, but the NPY Y5 receptor has been implicated in the mediation of this inhibitory effect. The NPY Y1/Y5 receptor agonist, [Leu(31),Pro(34)]NPY, was administered via cannula microinjections following light exposure during the early and late night. [Leu(31),Pro(34)]NPY significantly attenuated phase delays to light during the early night and blocked phase advances during the late night, in a manner similar to NPY. These results show the ability of NPY to attenuate phase shifts to light during the early night and block light-induced phase advances during the late night. Furthermore, this is the first in vivo study implicating the involvement of the NPY Y1/Y5 receptors in the complex interaction of photic and non-photic stimuli during the night. The alteration of photic phase shifts by NPY may influence photic entrainment within the circadian system.