Grid cell firing properties vary as a function of theta phase locking preferences in the rat medial entorhinal cortex

Theta rhythmic fluctuations in the hippocampal-entorhinal circuit are believed to reflect rapid transitions between modes of mnemonic processing. Specifically, activity at the trough and peak of CA1 pyramidal layer theta is thought to correspond to retrieval and encoding related processing, respectively. Spatially tuned "grid cells" in layers II and III of the medial entorhinal cortex preferentially spike during the trough and peak phases of theta, respectively. Such differences suggest differential involvement of these layers to the processes of retrieval and encoding. It remains unknown, however, if the properties of grid cells that spike preferentially at the trough vs. the peak of theta differ systematically. Such putative differences would offer insights into the differential processing that occurs during these two phases. The goal of the present work was to contrast these types of grid cells. We found that significant functional dissociations do exist: trough locked grid cells carried more spatial information, had a higher degree of head direction tuning, and were more likely to phase precess. Thus, grid cells that activate during the putative retrieval phase of theta (trough) have a greater degree of location, orientation, and temporal tuning specificity relative to grid cells that activate during the putative encoding phase (peak), potentially reflecting the influence of the retrieved content. Additionally, trough locked grid cells had a lower average firing rate, were more likely to burst, and were less phase locked to high-gamma (∼80 Hz). Further analyses revealed they had different waveforms profiles and that systemic blockade of muscarinic acetylcholine receptors reduced the spatial tuning of both types, although these differences were only significant for the peak locked grid cells. These differences suggest that trough and peak locked grid cells are distinct populations of neurons.