Aging affects GABAergic function and calcium homeostasis in the mammalian central clock

INTRODUCTION: Aging impairs the function of the central circadian clock in mammals, the suprachiasmatic nucleus (SCN), leading to a reduction in the output signal. The weaker timing signal from the SCN results in a decline in rhythm strength in many physiological functions, including sleep–wake patterns. Accumulating evidence suggests that the reduced amplitude of the SCN signal is caused by a decreased synchrony among the SCN neurons. The present study was aimed to investigate the hypothesis that the excitation/inhibition (E/I) balance plays a role in synchronization within the network. METHODS: Using calcium (Ca(2+)) imaging, the polarity of Ca(2+) transients in response to GABA stimulation in SCN slices of old mice (20–24 months) and young controls was studied. RESULTS: We found that the amount of GABAergic excitation was increased, and that concordantly the E/I balance was higher in SCN slices of old mice when compared to young controls. Moreover, we showed an effect of aging on the baseline intracellular Ca(2+) concentration, with higher Ca(2+) levels in SCN neurons of old mice, indicating an alteration in Ca(2+) homeostasis in the aged SCN. We conclude that the change in GABAergic function, and possibly the Ca(2+) homeostasis, in SCN neurons may contribute to the altered synchrony within the aged SCN network.