Comparison of properties of medial entorhinal cortex layer II neurons in two anatomical dimensions with and without cholinergic activation

Mechanisms underlying grid cell firing in the medial entorhinal cortex (MEC) still remain unknown. Computational modeling studies have suggested that cellular properties such as spike frequency adaptation and persistent firing might underlie the grid cell firing. Recent in vivo studies also suggest that cholinergic activation influences grid cell firing. Here we investigated the anatomical distribution of firing frequency adaptation, the medium spike after hyperpolarization potential (mAHP), subthreshold membrane potential oscillations, sag potential, input resistance and persistent firing, in MEC layer II principal cells using in vitro whole-cell patch clamp recordings in rats. Anatomical distributions of these properties were compared along both the dorso-ventral and medio-lateral axes, both with and without the cholinergic receptor agonist carbachol. We found that spike frequency adaptation is significantly stronger in ventral than in dorsal neurons both with and without carbachol. Spike frequency adaptation was significantly correlated with the duration of the mAHP, which also showed a gradient along the dorso-ventral axis. In carbachol, we found that about 50% of MEC layer II neurons show persistent firing which lasted more than 30 seconds. Persistent firing of MEC layer II neurons might contribute to grid cell firing by providing the excitatory drive. Dorso-ventral differences in spike frequency adaptation we report here are opposite from previous predictions by a computational model. We discuss an alternative mechanism as to how dorso-ventral differences in spike frequency adaptation could contribute to different scales of grid spacing.This work was supported by National Institute of Mental Health (NIMH) R01 MH61492, MH60013, ONR MURI N00014-10-1-0936, JSPS Postdoctoral Fellowship for Research Abroad and International Graduate School of Neuroscience, Ruhr University Bochum. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. (R01 MH61492 - National Institute of Mental Health (NIMH); MH60013 - National Institute of Mental Health (NIMH); N00014-10-1-0936 - ONR MURI; JSPS; International Graduate School of Neuroscience, Ruhr University Bochum)Published versio