Serotonin and feedback effects of behavioral activity on circadian rhythms in mice.

Wheel running activity can shorten the period (tau) of circadian rhythms in rats and mice. The role of serotonin (5HT), in this effect of behavior on circadian pacemaker function, was assessed by measuring tau during wheel-open and wheel-locked conditions in mice sustaining neurotoxic 5HT lesions directed at the suprachiasmatic nucleus (SCN). Intact mice exhibited a significant lengthening of tau (approximately 10 min) within 3 weeks when running wheels were locked. Mice with immunocytochemically confirmed 5HT depletion showed significantly longer tau than intact mice during wheel access, and did not show a significant change in tau up to 6 weeks after wheels were locked. In these mice, variability of tau across wheel access conditions was similar in magnitude to tau variability in intact mice at two time points without wheel access (+/- 3 min). 5HT-depleted mice also exhibited significantly longer activity periods (alpha), and a significantly delayed peak of activity within alpha. Previous studies show that a delayed peak of activity within alpha is associated with longer tau. Group differences in tau, and apparent failure of wheel-locking to lengthen tau in mice with 5HT lesions, may thus be due to loss of a serotonergic behavioral input pathway to the SCN, or to a lesion-induced change in the waveform of the activity rhythm.