Interval timing deficits and their neurobiological correlates in aging mice

Abstract

Age-related neurobiological and cognitive alterations suggest that interval timing (as a related function) is also altered in aging, which can, in turn, disrupt timing-dependent functions. We investigated alterations in interval timing with aging and accompanying neurobiological changes. We tested 4-6, 10-12, and 18-20 month-old mice on the dual peak interval procedure. Results revealed a specific deficit in the termination of timed responses (stop-times). The decision processes contributed more to timing variability (vs. clock/memory process) in the aged mice. We observed age-dependent reductions in the number of dopaminergic neurons in the VTA and SNc, cholinergic neurons in the medial septum/diagonal band (MS/DB) complex, and density of dopaminergic axon terminals in the DLS/DMS. Negative correlations were found between the number of dopaminergic neurons in the VTA and stop times, and the number of cholinergic neurons in MS/DB complex and the acquisition of stop times. Our results point at age-dependent changes in the decisional components of interval timing and the role of dopaminergic and cholinergic functions in these behavioral alterations.