SEROTONERGIC AFFERENTS MEDIATE ACTIVITY-DEPENDENT ENTRAINMENT OF THE MOUSE CIRCADIAN CLOCK

Serotonergic afferents mediate activity-dependent entrainment of the m ouse circadian clock. Am. J. Physiol. 273 (Regulatory Integrative Comp . Physiol. 42): R265-R269, 1997.-The circadian pacemaker located in th e suprachiasmatic nuclei (SCN) of the hypothalamus receives serotonerg ic afferents from the midbrain raphe nuclei, but the functional role o f this projection is unclear. In rodents, locomotor activity increases serotonin content in the SCN, and serotonergic agonists phase shift t he circadian clock in a manner closely similar to voluntary bouts of v igorous exercise, suggesting that serotonergic afferents could be part of the activity-dependent entrainment mechanism. We investigated this possibility by selectively lesioning serotonin terminals within and a djacent to the SCN by local microinjection of 5,7-dihydroxytryptamine in mice pretreated with desipramine. This treatment decreased serotoni n content 96 +/- 1% and 5-hydroxyindole-3-acetic acid content below le vels of detection (nearly 100%) but did not decrease norepinephrine co ntent or neuropeptide Y immunoreactivity in the SCN. These lesions did not alter subsequent running activity levels, yet rendered mice unabl e to synchronize to a regularly scheduled 2-h wheel running paradigm t hat entrained shamlesioned controls. Serotonin afferents are thus nece ssary for activity-dependent entrainment in the mouse.