In vivo monitoring of circadian timing in freely moving mice

In mammals, the principal circadian pacemaker driving daily physiology and behavioral rhythms is located in the suprachiasmatic nucleus (SCN) in the anterior hypothalamus [1]. The neural output of SCN is essential for the circadian regulation of behavioral activity [2,3]. Although remarkable progress has been made in revealing the molecular basis of circadian rhythm generation within the SCN [4-6], the output pathways by which the SCN exert control over circadian rhythms are not well understood. Most SCN efferents target the subparaventricular zone (SPZ), which resides just dorsal to the SCN [7, 8]. This output pathway has been proposed as a major component involved in the outflow for circadian regulation [9, 10]. We have examined the downstream pathway of the central clock by means of multiunit neural activity (MUA) [11] in freely moving mice. SCN neural activity is tightly coupled to environmental photic input and anticorrelated with MUA rhythm in the SPZ. In Clock mutant mice exhibiting attenuated circadian locomotor rhythmicity [12-14], MUA rhythmicity in the SCN and SPZ is similarly blunted. These results suggest that the SPZ plays a functional role in relaying circadian and photic signals to centers involved in generating behavioral activity.