AUTHOR=Hyman James M., Hasselmo Michael E., Seamans Jeremy K. TITLE=What is the Functional Relevance of Prefrontal Cortex Entrainment to Hippocampal Theta Rhythms? JOURNAL=Frontiers in Neuroscience VOLUME=5 YEAR=2011 URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2011.00024 DOI=10.3389/fnins.2011.00024 ISSN=1662-453X ABSTRACT=

There has been considerable interest in the importance of oscillations in the brain and in how these oscillations relate to the firing of single neurons. Recently a number of studies have shown that the spiking of individual neurons in the medial prefrontal cortex (mPFC) become entrained to the hippocampal (HPC) theta rhythm. We recently showed that theta-entrained mPFC cells lost theta-entrainment specifically on error trials even though the firing rates of these cells did not change (Hyman et al., 2010). This implied that the level of HPC theta-entrainment of mPFC units was more predictive of trial outcome than differences in firing rates and that there is more information encoded by the mPFC on working memory tasks than can be accounted for by a simple rate code. Nevertheless, the functional meaning of mPFC entrainment to HPC theta remains a mystery. It is also unclear as to whether there are any differences in the nature of the information encoded by theta-entrained and non-entrained mPFC cells. In this review we discuss mPFC entrainment to HPC theta within the context of previous results as well as provide a more detailed analysis of the Hyman et al. (2010) data set. This re-analysis revealed that theta-entrained mPFC cells selectively encoded a variety of task-relevant behaviors and stimuli while never theta-entrained mPFC cells were most strongly attuned to errors or the lack of expected rewards. In fact, these error responsive neurons were responsible for the error representations exhibited by the entire ensemble of mPFC neurons. A theta reset was also detected in the post-error period. While it is becoming increasingly evident that mPFC neurons exhibit correlates to virtually all cues and behaviors, perhaps phase-locking directs attention to the task-relevant representations required to solve a spatially based working memory task while the loss of theta-entrainment at the start of error trials may represent a shift of attention away from these representations. The subsequent theta reset following error commission, when coupled with the robust responses of never theta-entrained cells, could produce a potent error-evoked signal used to alert the rat to changes in the relationship between task-relevant cues and reward expectations.