Serotonin-containing fibers in the suprachiasmatic hypothalamus attenuate light-induced phase delays in mice.
Photic and non-photic stimuli phase shift and entrain circadian rhythms through distinct but interacting mechanisms which impinge on the suprachiasmatic nucleus (SCN), the circadian pacemaker. Our understanding of this mechanism is incomplete. Serotonin (5-HT) injected locally at the SCN reduces light-induced glutamate release and decreases the expression of c-fos, a marker of photic transduction. Furthermore, in SCN slices, 5-HT application reduces field potentials after optic nerve stimulation. We therefore predicted that 5-HT-terminal destruction restricted to the SCN would augment phase shifts of circadian rhythms induced by light exposure. To investigate this possibility, we compared photic phase delays and Fos-like immunoreactivity in mice which had previously received bilateral infusions directed at the SCN containing either the selective 5-HT neurotoxin 5,7-dihydroxytryptamine (DHT, n = 16) or vehicle (VEH, n = 12). Phase delays after a light pulse given during the mid-subjective night (30 lux, 30 min starting at circadian time (CT) 12-20) in DHT-mice were 50% greater than in VEH-mice (P = 0.017). DHT mice (n = 5) had 76% larger Fos responses to a mid-subjective night light pulse than VEH-mice (n = 5) (P = 0.029). We conclude that 5-HT at or near the SCN in mice reduces photic phase shifts and modulates the magnitude of the photic phase response in the mouse.
Bradbury
M J
MJ
Sleep Research Center, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, CA 94305, USA.
Dement
W C
WC
Edgar
D M
DM
D015116:5,7-Dihydroxytryptamine / Q000032:analysis; D000818:Animals; D001522:Behavior, Animal / Q000528:radiation effects; D002940:Circadian Rhythm / Q000528:radiation effects*; D008027:Light; D016014:Linear Models; D051379:Mice; D008810:Mice, Inbred C57BL; D009412:Nerve Fibers / Q000737:chemistry*; D011930:Reaction Time / Q000528:radiation effects*; D012701:Serotonin / Q000032:analysis*; D018490:Serotonin Agents / Q000032:analysis; D013493:Suprachiasmatic Nucleus / Q000737:chemistry*
D018490:Serotonin Agents; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin