Interval timing deficits and their neurobiological correlates in aging mice

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. •We investigated the effect of aging on timing in mice using dual peak procedure.•Old mice exhibited a deficit in the termination of timed responses (stop time).•Dopaminergic and cholinergic functions were compromised in old mice.•TH+ neuron number in VTA was associated with the stop time.•ChAT+ neuron number in MS/DB complex was associated with the acquisition of stop time.