title: Interval timing is intact in arrhythmic Cry1/Cry2-deficient mice.
abstract: Localizing the self in time is fundamental for daily life functioning and is lacking in severe disabling neuropsychiatric disorders like schizophrenia. Brains keep track of time across an impressive range of scales. Great progress has been made in identifying the molecular machinery of the circadian clock, the brain's master clock that operates on the 24-hour scale and allows animals to know the "time of the day" that important events occur, without referring to external cues. However, the biology of interval timing, the mechanism responsible for durations in the seconds-to-minutes-to-hours range, remains a mystery, and an obvious question is whether there is a common biological solution for keeping track of time across these 2 time scales. To address this, we trained Cry1/Cry2 double knockout mice on an interval timing task with durations that ranged between 3 and 27 seconds. The mice were kept under constant light conditions to avoid any exogenously induced form of daily rhythmicity. We observed that the homozygous knockouts displayed as accurate and precise a temporal memory as the control mice. This suggests that the Cry1 and Cry2 genes are not an important component of the interval timer. Furthermore, proper calibration of the interval timer does not depend on a functional circadian clock. Thus, these 2 timing systems likely rely on different and independent biological mechanisms.
authors.affiliation: Department of Neuroscience, Erasmus University Medical Center, Rotterdam, the Netherlands. stathis.papachristos@gmail.com
authors.forename: Efstathios B
authors.initials: EB
authors.lastname: Papachristos
authors.forename: Edwin H
authors.initials: EH
authors.lastname: Jacobs
authors.forename: Ype
authors.initials: Y
authors.lastname: Elgersma
mesh_terms: D000818:Animals; D002940:Circadian Rhythm / Q000235:genetics*; D056931:Cryptochromes / Q000235:genetics / Q000502:physiology*; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout
chemical_list: C538964:Cry1 protein, mouse; C538967:Cry2 protein, mouse; D056931:Cryptochromes