Evidence for Neuronal Desynchrony in the Aged Suprachiasmatic Nucleus Clock

作者：Sahar Farajnia, Stephan H. Michel, Tom Deboer, Henk Tjebbe vanderLeest, Thijs Houben, Jos H. T. Rohling, Ashna Ramkisoensing, Roman Yasenkov, Johanna H. Meijer · 发表于：Journal of Neuroscience · 年份：2012 · DOI：10.1523/jneurosci.0469-12.2012 · 被引用次数：234 · 研究领域：Circadian rhythm and melatonin、Sleep and Wakefulness Research、Electromagnetic Fields and Biological Effects

Aging is associated with a deterioration of daily (circadian) rhythms in physiology and behavior. Deficits in the function of the central circadian pacemaker in the suprachiasmatic nucleus (SCN) have been implicated, but the responsible mechanisms have not been clearly delineated. In this report, we characterize the progression of rhythm deterioration in mice to 900 d of age. Longitudinal behavioral and sleep-wake recordings in up to 30-month-old mice showed strong fragmentation of rhythms, starting at the age of 700 d. Patch-clamp recordings in this age group revealed deficits in membrane properties and GABAergic postsynaptic current amplitude. A selective loss of circadian modulation of fast delayed-rectifier and A-type K+ currents was observed. At the tissue level, phase synchrony of SCN neurons was grossly disturbed, with some subpopulations peaking in anti-phase and a reduction in amplitude of the overall multiunit activity rhythm. We propose that aberrant SCN rhythmicity in old animals--with electrophysiological arrhythmia at the single-cell level and phase desynchronization at the network level--can account for defective circadian function with aging.