Both the hippocampus and the medial prefrontal cortex are essential for successful performance in learning- and memory-related tasks. Within the hippocampus the theta rhythm plays an integral role in the timing of action potentials of hippocampal neurons responding to elements of any given task. Medial prefrontal cortex (mPFC) neurons display firing rate changes to specific facets of behavioral tasks (Jung et al., 1998. Cereb Cortex 8:437--450). We recorded units in the mPFC and field potentials in the hippocampus to determine whether behaviorally correlated mPFC cells fired with phase relationships to the hippocampal theta rhythm. In two different behavioral tasks (running a linear track and foraging in two distinct environments) we found mPFC cells that alternated between theta entrained firing and nonphasic firing depending on the ongoing behavior, while other cells were modulated during all conditions in both tasks. The majority of the mPFC cells with a significant correlation of firing rate changes with behavior were entrained to hippocampal theta. Cells that fired to specific events during only one direction of running were predisposed to theta modulation only in that direction. mPFC neurons have the capability to respond to behaviorally relevant elements by dynamically alternating between hippocampal theta entrained and nonphasic firing.

Performance of memory tasks is impaired by lesions to either the medial prefrontal cortex (mPFC) or the hippocampus (HPC); although how these two areas contribute to successful performance is not well understood. mPFC unit activity is temporally affected by hippocampal-theta oscillations, with almost half the mPFC population entrained to theta in behaving animals, pointing to theta interactions as the mechanism enabling collaborations between these two areas. mPFC neurons respond to sensory stimuli and responses in working memory tasks, though the function of these correlated firing rate changes remains unclear because similar responses are reported during mPFC dependent and independent tasks. Using a DNMS task we compared error trials vs. correct trials and found almost all mPFC cells fired at similar rates during both error and correct trials (92%), however theta-entrainment of mPFC neurons declined during error performance as only 17% of cells were theta-entrained (during correct trials 46% of the population was theta-entrained). Across the population, error and correct trials did not differ in firing rate, but theta-entrainment was impaired. Periods of theta-entrainment and firing rate changes appeared to be independent variables, and only theta-entrainment was correlated with successful performance, indicating mPFC-HPC theta-range interactions are the key to successful DNMS performance.