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

Abstract

Wheel running activity can shorten the period ( τ) 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 τ 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 τ (∼10 min) within 3 weeks when running wheels were locked. Mice with immunocytochemically confirmed 5HT depletion showed significantly longer τ than intact mice during wheel access, and did not show a significant change in τ up to 6 weeks after wheels were locked. In these mice, variability of τ across wheel access conditions was similar in magnitude to τ variability in intact mice at two time points without wheel access (±3 min). 5HT-depleted mice also exhibited significantly longer activity periods ( α), and a significantly delayed peak of activity within α. Previous studies show that a delayed peak of activity within α is associated with longer τ. Group differences in τ, and apparent failure of wheel-locking to lengthen τ 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.