Alterations in glutamatergic signalling contribute to the decline of circadian photoentrainment in aged mice

Robust physiological circadian rhythms form an integral part of wellbeing. The aging process has been found to negatively impact systems that drive circadian physiology, typically manifesting as symptoms associated with abnormal/ disrupted sleeping patterns. Here, we investigated the age-related decline in light-driven circadian entrainment in male C57BL/6J mice. We compared light-driven resetting of circadian behavioural activity in young (1-2 months) and old (14-18 months) mice and explored alterations in the glutamatergic pathway at the level of the circadian pacemaker, the suprachiasmatic nucleus (SCN). Aged animals showed a significant reduction in sensitivity to behavioural phase-resetting by light. We show that this change was through alterations in NMDA signalling at the SCN, where NMDA, a glutamatergic agonist, was less potent in inducing clock resetting. Finally, we show that this shift in NMDA sensitivity was through the reduced SCN expression of this receptor’s NR2B subunit. Only in young animals did an NR2B antagonist attenuate behavioural resetting. These results can help target treatments that aim to improve both physiological and behavioural circadian entrainment in aged populations.