Visible Exocytosis of the Non-Photic Signal Neuropeptide Y to the Suprachiasmatic Nucleus in Fasted Transgenic Mice Throughout Their Circadian Rhythms.

Organisms maintain circadian rhythms corresponding to approximately 24 h in the absence of external environmental cues, and they synchronize the phases of their autonomous circadian clocks to light-dark cycles, feeding timing, and other factors. The suprachiasmatic nucleus (SCN) occupies the top position of the hierarchy in the mammalian circadian system and functions as a photic-dependent oscillator, while the food-entrainable circadian oscillator (FEO) entrains the clocks of the digestive peripheral tissues and behaviors according to feeding timing. In mammals, neuropeptide Y (NPY) from the intergeniculate leaflet (IGL) neurons projected onto the SCN plays an important role in entraining circadian rhythms to feeding conditions. However, the relationship between the FEO and SCN has been unclear under various feeding conditions. In this study, novel NPY::Venus transgenic (Tg) mice, which expressed the NPY fused to Venus fluorescent protein, were generated to investigate the secretion of NPY on the SCN from the IGL. NPY-containing secretory granules with Venus signals in the SCN slices of the Tg mice could be observed using confocal and super-resolution microscopy. We observed that the number of NPY secretory granules released on the SCNs increased during fasting, and these mice were valuable tools for further investigating the role of NPY secretion from the IGL to the SCN in mediating interactions between the FEO and the SCN.