Neural correlates of interval timing in rodent prefrontal cortex.

Time interval estimation is involved in numerous behavioral processes, but its underlying neural mechanisms remain unclear. In particular, it has been controversial whether time is encoded on a linear or logarithmic scale. Based on our previous finding that inactivation of the medial prefrontal cortex (mPFC) profoundly impairs rat's ability to discriminate time intervals, we investigated how the mPFC processes temporal information by examining activity of mPFC neurons in rats performing a temporal bisection task. Many mPFC neurons conveyed temporal information based on monotonically changing activity profiles over time with negative accelerations, so that their activity profiles were better described by logarithmic than linear functions. Moreover, the precision of time-interval discrimination based on neural activity was lowered in proportion to the elapse of time, but without proportional increase in neural variability, which is well accounted for by logarithmic, but not by linear functions. As a population, mPFC neurons conveyed precise information about the elapse of time with their activity tightly correlated with the animal's choice of target. These results suggest that the mPFC might be part of an internal clock in charge of controlling interval-timing behavior, and that linearly changing neuronal activity on a logarithmic time scale might be one way of representing the elapse of time in the brain.