Daily electrical activity in the master circadian clock of a diurnal mammal

Abstract

AbstractDaily or circadian rhythms in mammals are orchestrated by a master circadian clock within the hypothalamic suprachiasmatic nuclei (SCN). Here, cell-autonomous oscillations in gene expression, intrinsic membrane properties, and synaptic communication shape the electrical landscape of the SCN across the circadian day, rendering SCN neurons overtly more active during the day than at night. This well-accepted hallmark bioelectrical feature of the SCN has overwhelmingly emerged from studies performed on a small number of nocturnal rodent species. Therefore, for the first time, we investigate the spontaneous and evoked electrical activity of SCN neurons in a diurnal mammal. To this end, we measured the electrical activity of individual SCN neurons during the day and at night in brain slices prepared from the diurnal murid rodent Rhabdomys pumilio and then developed cutting-edge data assimilation and mathematical modelling approaches to uncover the underlying ionic mechanisms. We find that R. pumilio SCN neurons were more excited in the day than at night, recapitulating the prototypical pattern of SCN neuronal activity previously observed in nocturnal rodents. By contrast, the evoked activity of R. pumilio neurons included a prominent suppressive response that is not present in the SCN of nocturnal rodents. Our computational modelling approaches reveal transient subthreshold A-type potassium channels as the primary determinant of the suppressive response and highlight a key role for this ionic mechanism in tuning excitability of clock neurons and optimising SCN function to accommodate R. pumilio’s diurnal niche.