title: Evidence for neuronal desynchrony in the aged suprachiasmatic nucleus clock.
abstract: 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.
authors.affiliation: Department of Neurophysiology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
authors.forename: Sahar
authors.initials: S
authors.lastname: Farajnia
authors.forename: Stephan
authors.initials: S
authors.lastname: Michel
authors.forename: Tom
authors.initials: T
authors.lastname: Deboer
authors.forename: Henk Tjebbe
authors.initials: HT
authors.lastname: vanderLeest
authors.forename: Thijs
authors.initials: T
authors.lastname: Houben
authors.forename: Jos H T
authors.initials: JH
authors.lastname: Rohling
authors.forename: Ashna
authors.initials: A
authors.lastname: Ramkisoensing
authors.forename: Roman
authors.initials: R
authors.lastname: Yasenkov
authors.forename: Johanna H
authors.initials: JH
authors.lastname: Meijer
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000367:Age Factors; D000375:Aging; D000704:Analysis of Variance; D000818:Animals; D001703:Biophysics; D002940:Circadian Rhythm / Q000502:physiology*; D004558:Electric Stimulation; D004569:Electroencephalography; D004576:Electromyography; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010507:Periodicity; D026902:Potassium Channel Blockers / Q000494:pharmacology; D012890:Sleep / Q000502:physiology; D012892:Sleep Deprivation; D013493:Suprachiasmatic Nucleus / Q000166:cytology*; D019789:Tetraethylammonium / Q000494:pharmacology; D014851:Wakefulness / Q000502:physiology
chemical_list: D026902:Potassium Channel Blockers; D019789:Tetraethylammonium