Long-range inhibitory axons from medial entorhinal cortex target lateral entorhinal neurons projecting to the hippocampus

Abstract

ABSTRACTFunctionally distinct information encoded by the two main divisions of the entorhinal cortex (EC), the lateral EC (LEC) and the medial EC (MEC), is thought to be first integrated at the level of the hippocampus. Here we examine a circuit connecting MEC to LEC that supports functional interplay at the level of the two entorhinal domains. Using a combination of anatomical,in vitroelectrophysiological and behavioral experiments in the mouse, we report that axons from MEC somatostatin-expressing GABAergic neurons densely distribute in layer I of LEC, where they drive strong and near selective inhibition of principal neurons in layer IIa. This inhibitory pathway is accompanied by MEC glutamatergic axons that innervate multiple layers of LEC and preferentially synapse onto principal neurons in layers IIb and III. Our findings indicate that excitatory and inhibitory projections from MEC may separately regulate the activity of different populations of hippocampal-projecting principal neurons in LEC.