CONICET | Buscador de Institutos y Recursos Humanos

We studied locomotor activity rhythms of C57/BL6 mice under a chronic jet-lag (CJL) protocol ChrA which consisted of 6-hour phase advances of the light-dark schedule (LD) every two days. Through periodogram analysis, we found two components of the activity rhythm: a short-period component (21.01±0.04h) that was entrained by the LD schedule, and a long-period component (24.68±0.26h). We developed a mathematical model comprising two coupled circadian oscillators that was tested experimentally with different CJL schedules. Our simulations suggested that under CJL, the system behaves as if it were under a zeitgeber with a period determined by [24 (phase shift size/days between shifts)]. Desynchronization within the system arises according to whether this effective period is inside or outside the range of entrainment of the oscillators. In this sense, ChrA is interpreted as a [24 6/2 = 21h] zeitgeber, and simulations predicted that a similar desynchronization pattern would appear under a 21h LD cycle. In effect, most animals studied under a T=21h zeitgeber showed two activity components as observed under ChrA: a short-period (21.00±0.03h) and a long-period component (24.19±0.18h). Simulations also predicted that desynchronization should be less prevalent under delaying than under advancing CJL. Indeed, most mice subjected to 6-h delay shifts every two days (an effective 27h zeitgeber) displayed a single entrained activity component (26.92±0.11h). Our results demonstrate that the disruption provoked by chronic jet-lag schedules is not dependent on the phase shift magnitude or the frequency of the shifts separately, but on the combination of both. In this study we present a novel model of forced desynchronization in mice under a specific CJL schedule; in addition, our model provides theoretical tools for the evaluation of circadian disruption under CJL conditions that are currently used in circadian research.

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