The above-described findings raise the question of how the hippocampus imposes theta phase-locking on mPFC. Understanding the cellular mechanisms of theta phase-locking will provide clues about how theta phase-locking in mPFC affects downstream areas that mediate behavior. A recent study addressed the cellular mechanism question by recording from mPFC pyramidal cells and inter-neurons during hippocampal theta rhythms [23••]. Pyramidal cells in mPFC preferentially fired at around the same theta phase as pyramidal cells in the ventral hippocampus, suggesting that ventral hippocampal pyramidal cells may directly activate mPFC pyramidal cells during theta states. Interestingly, mPFC basket cells, which target the somatic and proximal dendritic regions of pyramidal cells, preferentially discharged at this same portion of the theta cycle. This raises the possibility that feed-forward inhibition of mPFC pyramidal cells regulates the selection of task-relevant inputs during theta. Specifically, feed-forward inhibition may ensure that only the most excitable mPFC cells can fire before the onset of potent, basket cell-mediated inhibition. Paired pulse facilitation of mPFC responses to ventral hippocampal activation [10,15] would then ensure that the same population of cells is more strongly excited, and thus again selected, on the subsequent theta cycle.
