Working Memory Performance Correlates with Prefrontal-Hippocampal Theta Interactions but not with Prefrontal Neuron Firing Rates

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.