RT Journal Article SR Electronic T1 Anatomical and Electrophysiological Clustering of Superficial Medial Entorhinal Cortex Interneurons JF eneuro JO eNeuro FD Society for Neuroscience SP ENEURO.0263-16.2017 DO 10.1523/ENEURO.0263-16.2017 A1 Joan José Martínez A1 Bahar Rahsepar A1 John A. White YR 2017 UL http://www.eneuro.org/content/early/2017/10/06/ENEURO.0263-16.2017.abstract AB Local GABAergic interneurons regulate the activity of spatially-modulated principal cells in the medial entorhinal cortex (MEC), mediating stellate-to-stellate connectivity and possibly enabling grid formation via recurrent inhibitory circuitry. Despite the important role interneurons seem to play in the MEC cortical circuit, the combination of low cell counts and functional diversity has made systematic electrophysiological studies of these neurons difficult. For these reasons, there remains a paucity of knowledge on the electrophysiological profiles of superficial MEC interneuron populations. Taking advantage of GAD2-IRES-tdTomato and PV-tdTomato transgenic mice, we targeted GABAergic interneurons for whole-cell patch-clamp recordings and characterized their passive membrane features, basic input/output properties and action potential shape. These electrophysiologically characterized cells were then anatomically reconstructed, with emphasis on axonal projections and pial depth. K-means clustering of interneuron anatomical and electrophysiological data optimally classified a population of 106 interneurons into four distinct clusters. The first cluster is comprised of layer 2- and 3-projecting, slow-firing interneurons. The second cluster is comprised largely of PV+ fast-firing interneurons that project mainly to layers 2 and 3. The third cluster contains layer 1- and 2-projecting interneurons, and the fourth cluster is made up of layer 1-projecting horizontal interneurons. These results, among others, will provide greater understanding of the electrophysiological characteristics of MEC interneurons, help guide future in vivo studies, and may aid in uncovering the mechanism of grid field formation.Significance Statement Despite the critical role that entorhinal inhibitory interneurons play in computation and grid cell formation, the electrophysiological properties of this inhibitory interneuron population remain largely uncharacterized. This study describes systematically the electrophysiology and anatomy of the inhibitory cells in the medial entorhinal cortex and introduces a grouping framework for the population. This framework divides the interneuron population into four clusters, based on differences in their axonal projections and electrophysiological properties. These findings confirm and extend findings from previous anatomic studies and will inform future studies of medial entorhinal interneurons.