Interval Timing Is Preserved Despite Circadian Desynchrony in Rats: Constant Light and Heavy Water Studies

Abstract

The mechanisms that enable mammals to time events that recur at 24-h intervals (circadian timing) and at arbitrary intervals in the seconds-to-minutes range (interval timing) are thought to be distinct at the computational and neurobiological levels. Recent evidence that disruption of circadian rhythmicity by constant light (LL) abolishes interval timing in mice challenges this assumption and suggests a critical role for circadian clocks in short interval timing. We sought to confirm and extend this finding by examining interval timing in rats in which circadian rhythmicity was disrupted by long-term exposure to LL or by chronic intake of 25% DO. Adult, male Sprague-Dawley rats were housed in a light-dark (LD) cycle or in LL until free-running circadian rhythmicity was markedly disrupted or abolished. The rats were then trained and tested on 15- and 30-sec peak-interval procedures, with water restriction used to motivate task performance. Interval timing was found to be unimpaired in LL rats, but a weak circadian activity rhythm was apparently rescued by the training procedure, possibly due to binge feeding that occurred during the 15-min water access period that followed training each day. A second group of rats in LL were therefore restricted to 6 daily meals scheduled at 4-h intervals. Despite a complete absence of circadian rhythmicity in this group, interval timing was again unaffected. To eliminate all possible temporal cues, we tested a third group of rats in LL by using a pseudo-randomized schedule. Again, interval timing remained accurate. Finally, rats tested in LD received 25% DO in place of drinking water. This markedly lengthened the circadian period and caused a failure of LD entrainment but did not disrupt interval timing. These results indicate that interval timing in rats is resistant to disruption by manipulations of circadian timekeeping previously shown to impair interval timing in mice.

Circadian modulation of motivation in mice

“…This effect of decreased motivation J o u r n a l P r e -p r o o f is mainly motivational/rewarding rather than motor, since in the operant conditioning phase there were no significant differences between groups (data not shown). These results complement previous studies from our group indicating that circadian arrhythmicity induces loss of temporal control in an interval timing task in mice involving food reward [18,35] (but see [43]). The low motivation found in mice under LL conditions was comparable to the levels displayed by the mice tested during the light phase of the LD cycle for young mice and, for aged mice, intermediate between diurnal and nocturnal levels.…”

Multiple entrained oscillator model of food anticipatory circadian rhythms

“…The Gaussian distribution of unreinforced lever pressing evident during meal omission tests in the present study is reminiscent of response distributions generated by rats and mice working for food under fixed, short interval reinforcement schedules (seconds to minutes range; e.g. 27 ). In other respects, food anticipatory rhythms observed here and in other studies of circadian feeding schedules are distinct from anticipatory responding to short non-circadian intervals.…”

Interval timing is disrupted in female 5xFAD mice: An indication of altered memory processes

“…Most relevant to this procedural aspect of the current study, the effects of testing interval timing performance at different times of day were reported in both rodents and humans (see Agostino, Golombek, & Meck, for a review). For instance, the accuracy of temporal judgments was found to be higher when mice were tested during the dark cycle (Agostino, Nascimento, Bussi, Eguía, & Golombek, ) and the desynchronization of circadian rhythms was found to disrupt interval timing (Agostino, Nascimento, et al, ; but see Cordes & Gallistel, ; Petersen & Mistlberger, ). Time‐of‐the‐day testing effects and/or circadian effects on interval timing are beyond the scope of the current study; however, readers should note that disruption in circadian rhythms is evident in AD (Milán‐Tomás & Shapiro, ) and 5xFAD mouse model is known to have disruptions in their sleep–wake cycle (Sethi et al, ).…”