Probabilistic Information Modulates the Timed Response Inhibition Deficit in Aging Mice

Abstract

How interval timing is affected by aging constitutes one of the contemporary research questions. There is however a limited number of studies that investigate this research question in animal models of aging. The current study investigated how temporal decision-making is affected by aging. Initially, we trained young (2–3 month-old) and old C57BL/6J male mice (18–19 month-old) independently with short (3 s) and long (9 s) intervals by signaling, in each trial, the hopper associated with the interval that is in effect in that trial. The probability of short and long trials was manipulated (0.25 or 0.75) for different animals in each age group. During testing, both hoppers were illuminated, and thus active trial type was not differentiated. We expected mice to spontaneously combine the independently acquired time interval-location-probability information to adaptively guide their timing behavior in test trials. This adaptive ability and the resultant timing behavior were analyzed and compared between the age groups. Both young and old mice indeed adjusted their timing behavior in an abrupt fashion based on the independently acquired temporal-spatial-probabilistic information. The core timing ability of old mice was also intact. However, old mice had difficulty in terminating an ongoing timed response when the probability for the short trial was higher and this difference disappeared in the group that was exposed to a lower probability of short trials. These results suggest an inhibition problem in old mice as reflected through the threshold modulation process in timed decisions, which is cognitively penetrable to the probabilistic information.