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
El. Meyer-bernstein et Lp. Morin, 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, NEUROSCIENC, 92(1), 1999, pp. 267-279
Several pharmacological studies have suggested that the large median raphe
serotonergic projection to the circadian clock in the suprachiasmatic nucle
us may modulate circadian rhythm phase. The present experiments studied the
role of dorsal and median raphe nuclei as regulators of circadian rhythmic
ity by evaluating the ability of electrical stimulation to shift rhythm pha
se or to alter photic induction of FOS protein synthesis. Male hamsters imp
lanted 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 pr
eviously demonstrated, light alone induces FOS immunoreactivity in nuclei o
f suprachiasmatic nucleus neurons. This was significantly attenuated by sti
mulation of either the median or dorsal raphe nucleus, with the extent of a
ttenuation proportional to the intensity of stimulation. Electrical stimula
tion 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 i
n the hippocampus. In a second experiment, hamsters housed with running whe
els 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 onse
t. Regardless of which raphe nucleus was electrically stimulated, approxima
tely 22 min phase advances were elicited at CT6 and 36 min phase delays wer
e 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 ab
ility 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. (C) 1999 IBRO. Pub
lished by Elsevier Science Ltd.