Light and GABA)(A) receptor activation alter period mRNA levels in the SCN of diurnal Nile grass rats.
We examined Period (Per) mRNA rhythms in the suprachiasmatic nucleus (SCN) of a diurnal rodent and assessed how phase-shifting stimuli acutely affect SCN Per mRNA using semiquantitative in situ hybridization. First, Per1 and Per2 varied rhythmically in the SCN over the course of one circadian cycle in constant darkness: Per1 mRNA was highest in the early to mid-subjective day, while Per2 mRNA levels peaked in the late subjective day. Second, acute light exposure in the early subjective night significantly increased both Per1 and Per2 mRNA. Third, Per2 but not Per1 levels decreased 1 and 2 h after injection of the gamma-aminobutyric acid (GABA)(A) receptor agonist muscimol into the SCN during the subjective day. Fourth, muscimol also reduced the light-induced Per2 in the early subjective night, but Per1 induction by light was not significantly affected. Consistent with previous studies, these data demonstrate that diurnal and nocturnal animals show very similar daily patterns of Per mRNA and light-induced Per increases in the SCN. As with light, muscimol alters circadian phase, and daytime phase alterations induced by muscimol are associated with significant decreases in Per2 mRNA. In diurnal animals, muscimol-induced decreases in Per are associated with phase delays rather than advances. The direction of the daytime phase shift may be determined by the relative suppression of Per1 vs. Per2 in SCN cells. As in nocturnal animals, changes in Per1 and Per2 mRNA by photic and non-photic stimuli appear to be associated with circadian phase alteration.
Novak
Colleen M
CM
Endocrine Research Unit, Mayo Clinic and Foundation, Rochester, MN, USA. Novak.Colleen@mayo.edu
Ehlen
J Christopher
JC
Paul
Ketema N
KN
Fukuhara
Chiaki
C
Albers
H Elliott
HE
D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002940:Circadian Rhythm / Q000235:genetics*; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D017403:In Situ Hybridization / Q000379:methods; D008027:Light; D008297:Male; D008845:Microinjections / Q000379:methods; D009118:Muscimol / Q000494:pharmacology; D010775:Photic Stimulation / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism*; D013493:Suprachiasmatic Nucleus / Q000378:metabolism*; D013997:Time Factors
D018797:Cell Cycle Proteins; D018755:GABA Agonists; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D009118:Muscimol