Dopamine signaling: the missing link between circadian and interval timing

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

Huerta Grande, Córdoba

Congreso; XXIX Congreso Anual de la Sociedad Argentina de Investigación en Neurociencia; 2014

Sociedad Argentina de Investigación en Neurociencia

Two of the main biological timing mechanisms operate in the second-to-minute (interval timing) and on a daily basis (circadian rhythms). Interval timing involves the interaction of cortico-striatal circuits via dopaminergic pathways, while circadian rhythms modulate physiological and behavioural functions. We have previously reported that circadian disruption impairs interval timing in mice. In this work we studied the involvement of dopamine signaling in the interaction between both timing systems. We found that levodopa injections improved timing performance in mice with circadian disruptions, suggesting that a daily increase of dopamine is necessary for a correct performance. Moreover, striatal dopamine levels exhibited a daily rhythm under light/dark (LD) conditions, with higher levels during the night. This rhythm was abolished by constant light (LL). We also demonstrated a daily oscillation in tyrosine hydroxylase levels, dopamine turnover and the circadian clock gene Per2 in the striatum and substantia nigra. In all cases, these oscillations were lost under LL. We also found a daily oscillation of striatal dopamine receptor D2 mRNA, and we are currently studying D2R protein levels. Our results suggest that the lack of rhythmicity in dopamine signaling could be responsible for impaired performance in the timing task, and add further support to the notion that circadian and interval timing share some common processes, interacting at the level of the dopaminergic system.