Electrical stimulation of the median or dorsal raphe nuclei reduces light-induced FOS protein in the suprachiasmatic nucleus and causes circadian activity rhythm phase shifts.

Several pharmacological studies have suggested that the large median raphe serotonergic projection to the circadian clock in the suprachiasmatic nucleus may modulate circadian rhythm phase. The present experiments studied the role of dorsal and median raphe nuclei as regulators of circadian rhythmicity by evaluating the ability of electrical stimulation to shift rhythm phase or to alter photic induction of FOS protein synthesis. Male hamsters implanted with bipolar electrodes in either the median or dorsal raphe nucleus were stimulated during the early subjective night coincident with exposure to a saturating light pulse. About 90 min later, animals were anesthetized, perfused and the brains processed for FOS protein immunoreactivity. As previously demonstrated, light alone induces FOS immunoreactivity in nuclei of suprachiasmatic nucleus neurons. This was significantly attenuated by stimulation of either the median or dorsal raphe nucleus, with the extent of attenuation proportional to the intensity of stimulation. Electrical stimulation without light exposure had no effect on FOS expression. The effect of light on FOS expression in the suprachiasmatic nucleus was not modified by pre-treatment with the 5-HT1/2 serotonin receptor antagonist, metergoline, although it greatly reduced electrical stimulation-induced FOS expression in the hippocampus. In a second experiment, hamsters housed with running wheels in constant light were electrically stimulated in the median or dorsal raphe nucleus 6 h prior to (CT6) or 2 h after (CT14) expected activity onset. Regardless of which raphe nucleus was electrically stimulated, approximately 22 min phase advances were elicited at CT6 and 36 min phase delays were elicited at CT14. Despite the fact that the sole direct projection from the raphe complex to the suprachiasmatic nucleus is from the median nucleus, the present data do not distinguish between the median and dorsal raphe with respect to their impact on circadian rhythm regulation. Instead, two possible roles for each raphe nucleus are demonstrated. One main effect is that both raphe nuclei modulate rhythm phase. The second is an interaction between raphe efferent activity and light which, in the present studies, is demonstrated by the ability of raphe stimulation to modulate the action of light on the circadian system. While serotonin is a likely neurotransmitter mediating one or both effects, alternatives such as GABA, must be considered.