Modulation of interval timing by the circadian system:Role of melatonin and dopaminergic function

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

New Orleans

Congreso; 2012 Neuroscience Meeting Planner; 2012

Society for Neuroscience

Temporal perception is fundamental to environmental adaptation in humans and other animals. Duration discrimination within the seconds-to-minutes range-known as interval timing-involves the interaction of the basal ganglia and the prefrontal cortex via dopaminergic-glutamatergic pathways.Besides interval timing, most-if not all-organisms exhibit circadian rhythms with periods close to 24 h.The circadian system modulates performance in several cognitive tasks. We have previously reported that both circadian disruption and desynchronization leading to non-optimal circadian test time, impaired performance of mice in a 24-s peak-interval timing task (Agostino et al, 2011, Brain Res 1370:154). In this work we studied the involvement of dopamine signaling in the interaction between circadian and interval timing, and the role of melatonin as a key element in the regulation of this signaling pathway. Striatal dopamine levels measured by HPLC-ED indicated a daily rhythm under light/dark (LD) conditions in C57BL/6 mice, with lower levels during the day and a peak during the night.This daily variation was affected by inducing circadian disruption under constant light (LL) conditions. Moreover, daily injections of L-DOPA improved timing performance in the peak-interval (PI) procedure in mice with circadian disruptions, suggesting that a daily increase of dopamine is necessary foe a correct performance in the timing task. Melatonin, a nocturnal hormone driven by the circadian system, has been reported to affect dopamine signaling in nocturnal rodents. Our results show impaired learning in the 24-s peak intrval timing task in pinealectomized Wistar rats, indicating that melatonin could be of importance to modulate interval timing on a circadian base. Our findings ass further support to the notion that circadian and interval timing probably share some common processes, interacting to some extent at the level of the dopaminergic system.