Differential roles of medial/lateral entorhinal cortex in spatial/object memory and contribution to hippocampal functional neuronal organization

Episodic memory is subserved by interactions between entorhinal cortex (EC) and hippocampus. Within EC, a functional dissociation has been proposed for medial (MEC) and lateral (LEC) subregions, whereby, MEC processes spatial information while LEC processes information about objects and their location in space. Most of these studies, however, used classical methods which lack both spatial and temporal specificity, thus, the precise role of MEC/LEC in memory could use further clarification. First, we show a possible functional dissociation of MEC/LEC for place/object fear memory, by optogenetic suppression of these areas during memory acquisition. The main output of EC is to the hippocampus. MEC projects mainly towards proximal/superficial CA1 and deep CA3 while LEC towards distal/deep CA1 and superficial CA3. Dentate gyrus (DG), terminations of MEC/LEC are dissociated septotemporally. A functional dissociation has also been proposed for subregions of the hippocampus. Previous studies reported that proximal/distal CA1 process spatial/nonspatial information, respectively. For the second part of the study, we used the immediate-early gene Zif-268 to map neuronal activity in CA1. We first show enhanced Zif-268 expression and cluster-type organization in the proximal CA1 by place exposure and enhanced Zif-268 expression/cluster organization in distal CA1 following object exposure. Second, direct optogenetic stimulation of MEC/LEC, produced a similar enhancement/cluster-type organization in the same areas. Enhanced Zif-268 expression was also observed in CA3 and DG. These results substantiate previous findings and are proof positive that the hippocampus is organized in clusters to encode information generally ascribed to this structure.