Circadian modulation of interval timing: role of melatonin and dopaminergic function

AGOSTINO P.V.; BUSSI I.L.; LEVÍN, G; GOLOMBEK D.A.

Destin (Florida)

Congreso; 13th Meeting of Society for Research on Biological Rhythms; 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, striatum and prefrontal cortex. We have previously reported that short-time perception in mice is influenced by the circadian pacemaker [2]. In this work we tested the hypothesis that dopamine signaling is involved in the interaction between circadian and interval timing, being melatonin a key element in the regulation of these signaling pathways. Animals were trained following the peak-interval (PI) procedure [3]. As we previously reported, mice under constant light (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. Moreover, we found a daily rhythm in dopamine levels under light/dark (LD) conditions, with lower levels during the day and a peak during the night. Under constant light, this variation persisted but with a different phase compared to LD. Melatonin has been reported to affect dopamine signaling. In this sense, results show significant differences in the estimation of 24-second intervals in rats without an intact pineal gland versus control animals. We are currently studying the circadian expression of clock genes ? such as Per2 ? in pre-frontal cortex and basal ganglia. A model of the circadian influence on interval timing is proposed. 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.