Circadian modulation of interval timing in mice

AGOSTINO P.V.

Querétaro

Simposio; First Symposium on the Neurophysiology of Interval Timing; 2012

Temporal perception is fundamental to environmental adaptation in humans and other animals. To deal with timing, organisms have developed multiple systems that are active over a wide range of magnitude, the most important being circadian timing, interval timing and millisecond timing [1]. Time estimation in the second-to-minutes range (known as interval timing) involves the interaction of the basal ganglia and the prefrontal cortex. We have previously reported that short-time perception in mice is not independent of the influence of the circadian pacemaker [2]. In this work we tested the hypothesis that dopamine signaling is involved in the interaction between circadian and interval timing. Animals were trained following the peak-interval (PI) procedure [3]. Results show significant differences in the estimation of 24-second intervals at different times of day, being more accurate the group trained at night. Interval timing was also studied in animals under constant light (LL) conditions, which abolish circadian activity and temperature rhythms. Mice under LL conditions were unable to acquire temporal control in the peak interval procedure. However, daily injections of L-DOPA before the experiment improved timing performance in LL mice, suggesting that an increase of dopamine is necessary for the interval to be timed. We are currently studying the circadian regulation of dopamine levels in the striatum, as well as the expression of clock genes ? such as Per2 ? in pre-frontal cortex and basal ganglia. References: [1] Buhusi CV and Meck WH (2005). Nature Reviews 6:755-765. [2] Agostino et al. (2010). Brain Res. 1370:154-63. [3] Cheng RK and Meck WH (2007). Brain Res. 1186:242-254. Keywords: circadian rhythms, interval timing, cortico-striatal circuits.