Encoding the ins and outs of circadian pacemaking.

ABSTRACT

The SCN of the mammalian hypothalamus comprises a self-sustained, biological clock that generates endogenous ca. 24-h (circadian) rhythms. Circadian rhythmicity in the SCN originates from the interaction of a defined set of "clock genes" that participate in transcription/translation feedback loops. In order for the SCN to serve as an internal clock that times an internal day corresponding to the external solar day, the intracellular molecular oscillations must be output as physiological signals and be reset by appropriate environmental inputs. Here, the authors consider the mechanisms by which the SCN circadian pacemaker encodes rhythmic output and light input. In particular, they focus on the ionic mechanisms by which SCN neurons encode clock gene output as circa-dian rhythms in spike frequency, as well as cellular and molecular mechanisms by which SCN neurons encode circadian light input through phase heterogeneity in the SCN network. The authors propose that there are 2 distinct classes of ionic mechanisms supporting spike frequency rhythms output--modulation of basal membrane potential and conductance versus modulation of spike production--whereas light input is transformed by cellular communication within the SCN network and encoded by the relative phase relationships among SCN neurons.