Evidence for neuronal desynchrony in the aged suprachiasmatic nucleus clock

• Published in: The Journal of neuroscience Vol. 32; no. 17; pp. 5891 - 5899
• Main Authors: Farajnia, Sahar, Michel, Stephan, Deboer, Tom, vanderLeest, Henk Tjebbe, Houben, Thijs, Rohling, Jos H T, Ramkisoensing, Ashna, Yasenkov, Roman, Meijer, Johanna H
• Format: Journal Article
• Language: English
• Published: United States Society for Neuroscience 25.04.2012
• Subjects: Action Potentials - drug effects; Action Potentials - physiology; Age Factors; Aging; Analysis of Variance; Animals; Biophysics; Circadian Rhythm - physiology; Electric Stimulation; Electroencephalography; Electromyography; In Vitro Techniques; Male; Mice; Mice, Inbred C57BL; Motor Activity - drug effects; Motor Activity - physiology; Neurons - drug effects; Neurons - physiology; Patch-Clamp Techniques; Periodicity; Potassium Channel Blockers - pharmacology; Sleep - physiology; Sleep Deprivation; Suprachiasmatic Nucleus - cytology; Tetraethylammonium - pharmacology; Wakefulness - physiology
• ISSN: 0270-6474; 1529-2401; 1529-2401
• DOI: 10.1523/jneurosci.0469-12.2012

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.