Circadian modulation of interval timing in mice

P.V. AGOSTINO; M. DO NASCIMENTO; M.C. EGUíA; D.A. GOLOMBEK.

Buzios, Brasil

Congreso; I IBRO/LARC Congress of Neurosciences of Latin America, the Caribbean and Iberian Peninsula; 2008

Timing and time perception are fundamental to survival and goal reaching in humans and other animals. To deal with timing, organisms have developed multiple systems that are active over a range of 10 orders of magnitude, the most important being circadian timing, interval timing and millisecond timing [1]. The circadian pacemaker is located in the suprachiasmatic nuclei (SCN) of the hypothalamus, and is driven by a self-sustaining oscillator with a period near to 24 h. The estimation of time in the second-to-minutes range ? known as interval timing ? involves the interaction of the basal ganglia and the prefrontal cortex. There are several evidences indicating a possible link between circadian and interval timing [2-7]. In this work we tested the hypothesis that interval timing is sensitive to circadian modulations. The ability of mice to estimate time intervals of short duration was examined. Animals were trained following the protocol of Drew et al [8], slightly modified. Briefly, mice were trained in three consecutive phases - pre-training, fixed interval training and peak interval training - during approximately 60 days. Two independent experiments were conducted, in which mice were trained in the middle of the diurnal phase (ZT 5-7, group 1) or in the middle of the nocturnal phase (ZT 17-19, group 2). Our preliminary results show significant differences in the estimation of 24-second intervals at different times of day. Currently we are studying the estimation of time throughout the circadian cycle, as well as interval timing in animals subjected to circadian desynchronizations. We also aim to develop theorical models which tell about the mechanisms involved in interval timing. [1] Buhusi CV and Meck WH (2005). Nature Reviews 6: 755-765. [2] Silver R and Bittman EL (1984). Ann. N. Y. Acad. Sci. 423: 488-514. [3] Aschoff, J. (1985). Hum. Neurobiol. 4: 41-52. [4] Chandrashekaran ÌÊ, et al. (1991). J. Biosci. 16 (3): 97-101. [5] Pati AK and Gupta S. (1994). J. Biosci. 19 (3): 325-330. [6] Crystal J. (2001). J. Exp. Psychol. 27: 68-78. [7] Kuriyama K, et al. (2005). Neurosci. Res. 53: 123-128. [8] Drew MR, et al. (2007). J. Neurosci 27(29): 7731-7739.