Although the suprachiasmatic nucleus (SCN) has long been considered the master circadian clock in mammals, the topology of the connections that synchronize daily rhythms among SCN cells is not well understood. We combined experimental and computational methods to infer the directed interactions that mediate circadian synchrony between regions of the SCN. We analyzed PERIOD2 (PER2) expression from SCN slices during and after treatment with tetrodotoxin, allowing us to map connections as cells resynchronized their daily cycling following blockade and restoration of cell-cell communication. Using automated analyses, we found that cells in the dorsal SCN stabilized their periods slower than those in the ventral SCN. A phase-amplitude computational model of the SCN revealed that, to reproduce the experimental results: (1) the ventral SCN had to be more densely connected than the dorsal SCN and (2) the ventral SCN needed strong connections to the dorsal SCN. Taken together, these results provide direct evidence that the ventral SCN entrains the dorsal SCN in constant conditions.
Keywords: Circadian; Period gene; SCN; computational model; entrainment; vasoactive intestinal polypeptide; vasopressin.