LIGHT-INDUCED PHASE-SHIFTS OF CIRCADIAN ACTIVITY RHYTHMS AND IMMEDIATE-EARLY GENE-EXPRESSION IN THE SUPRACHIASMATIC NUCLEUS ARE ATTENUATED IN OLD C3H HEN MICE/

Alterations in the mechanisms of entrainment and/or response of the ci rcadian pacemaker to zeitgebers may contribute to age related changes in sleep/wake rhythms. This study examined the effect of age on Light- induced phase shifts of circadian activity rhythms and on the expressi on of the immediate early genes c-fos and jun-B in the suprachiasmatic nucleus (SCN) of young and old C3H/HeN mice. Mice (4 months or 16 mon ths at the beginning of the experiment) were housed in constant darkne ss with circadian rhythms assessed by running wheel activity. Mice wer e exposed to light pulses of 30, 100, 300 or 1000 lux and steady state phase shifts of circadian activity rhythms determined. In young mice exposed to light at circadian time (CT) 14, light pulses of 30, 100, 3 00 or 1000 lux induced phase delays of circadian activity rhythms of s imilar magnitude (averaging 2.8 h). Phase delays following photic stim ulation were reduced in the old mice at all light levels (averaging 1. 1 h, P < 0.001). Following behavioral testing, mice were exposed to li ght (1000 lux) at CT 14 for determination of the light-induced express ion of c-fos and jun-B mRNA in the SCN by in situ hybridization histoc hemistry. Immediate early gene expression following light exposure was reduced by 42% (c-fos) and 48% (jun-B) in the SCN of old mice compare d to young controls (P < 0.001). Together, these results suggest an ag e related reduction in responsiveness to light by the circadian pacema ker.