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.

Inhibitory interneurons are thought to play crucial roles in diverse brain functions. However, roles of different inhibitory interneuron subtypes in working memory remain unclear. We found distinct activity patterns and stimulation effects of two major interneuron subtypes, parvalbumin (PV)- and somatostatin (SOM)-expressing interneurons, in the medial prefrontal cortex of mice performing a spatial working memory task. PV interneurons showed weak target-dependent delay-period activity and were strongly inhibited by reward. By contrast, SOM interneurons showed strong target-dependent delay-period activity, and only a subtype of them was inhibited by reward. Furthermore, optogenetic stimulation of PV and SOM interneurons preferentially suppressed discharges of putative pyramidal cells and interneurons, respectively. These results indicate different contributions of PV and SOM interneurons to prefrontal cortical circuit dynamics underlying working memory.

Although the medial prefrontal cortex (mPFC) is known to play a crucial role in rodent social behavior, little is known about mPFC neural correlates of social behavior. In the present study, we examined single-neuron activity in the mPFC of mice performing a modified version of the three-chamber test. We found that a subset of mPFC neurons elevate discharge rates when approaching a stranger mouse but not when approaching an inanimate object or an empty chamber. Our results reveal mPFC neural activity that is correlated with social approach behavior in a widely used social-interaction paradigm. These findings might be helpful for future investigations of mPFC neural processes underlying social interaction in health and disease.

Newly experienced events are often remembered together with how rewarding the experiences are personally. Although the hippocampus is a candidate structure where subjective values are integrated with other elements of episodic memory, it is uncertain whether and how the hippocampus processes value-related information. We examined how activity of dorsal CA1 and dorsal subicular neurons in rats performing a dynamic foraging task was related to reward values that were estimated using a reinforcement learning model. CA1 neurons carried significant signals related to action values before the animal revealed its choice behaviorally, indicating that the information on the expected values of potential choice outcomes was available in CA1. Moreover, after the outcome of the animal's goal choice was revealed, CA1 neurons carried robust signals for the value of chosen action and they temporally overlapped with the signals related to the animal's goal choice and its outcome, indicating that all the signals necessary to evaluate the outcome of an experienced event converged in CA1. On the other hand, value-related signals were substantially weaker in the subiculum. These results suggest a major role of CA1 in adding values to experienced events during episodic memory encoding. Given that CA1 neuronal activity is modulated by diverse attributes of an experienced event, CA1 might be a place where all the elements of episodic memory are integrated.

We have shown previously that CA1 conveys significant neural signals necessary to update value of the chosen target, namely chosen value and reward signals. To better understand hippocampal neural processes related to valuation, we compared chosen value- and reward-related neural activity between the CA3 and CA1 regions. Single units were recorded with tetrodes from the dorsal CA3 and CA1 regions of rats performing a dynamic foraging task, and chosen value- and reward-related neural activity was estimated using a reinforcement learning model and multiple regression analyses. Neural signals for chosen value and reward converged in both CA3 and CA1 when a trial outcome was revealed. However, these neural signals were stronger in CA1 than CA3. Consequently, neural signals for reward prediction error and updated chosen value were stronger in CA1 than CA3. Together with our previous finding that CA1 conveys stronger value signals than the subiculum, our results raise the possibility that CA1 might play a particularly important role among hippocampal subregions in evaluating experienced events.