DISTINCT MEC AND LEC SUBPOPULATIONS UNDERLIE FUNCTIONAL SEGREGATION OF THE SUPRA- AND INFRAPYRAMIDAL BLADE OF THE DENTATE GYRUS IN SPATIAL AND NON-SPATIAL INFORMATION PROCESSING

Recent studies have identified subnetworks along the proximodistal axis of the hippocampal CA1 and CA3 subfields that preferentially process spatial or non-spatial information (Nakamura et al., 2013; Beer and Vavra et al., 2018; Ku et al., 2024). Anatomical evidence suggests that the supra- and infrapyramidal blades of the dentate gyrus (DG) differentially contribute to these functional subnetworks, and that this segregation might be traced back to distinct entorhinal (EC) inputs. Using optogenetic silencing and Arc immediate early gene imaging, we demonstrate that the suprapyramidal blade preferentially supports spatial information processing, whereas the infrapyramidal blade supports non-spatial discrimination, and that each blade differentially contributes to CA3–CA1 subnetworks. Furthermore, using retrograde tract tracing in cleared brains, we identify distinct dorsoventral neuronal populations in the medial and lateral entorhinal cortices (MEC and LEC) that selectively innervate the supra- and infrapyramidal blades. Consistently, Arc expression patterns during memory recall in these EC subpopulations mirror the functional segregation observed in the DG, in terms of spatial and non-spatial processing. Together, these findings identify the DG blades as distinct circuit elements that enable preferential processing of spatial and non-spatial information within hippocampal–entorhinal networks.