Spatial and non-spatial memory subnetworks in the medial temporal lobe : focus on the dentate gyrus

Abstract

Remembering past unique experiences - episodic memory - is an important aspect of our daily lives. Recent anatomical and functional evidence supports a new model for episodic memory, which posits that spatial and non-spatial aspects of memories might be processed by distinct subnetworks segregated along the proximodistal axis of the hippocampus. This model of segregated information processing might be relevant when one of the dimensions of a given memory, i.e. spatial or non-spatial, is overly important compared to the other and the integration of the least important information is dispensable. According to this model, the spatial subnetwork consists of the enclosed blade of the dentate gyrus (DG), the distal part of CA3, and the proximal part of CA1. The non-spatial subnetwork, on the other hand, comprises the exposed blade of the DG, proximal CA3 and distal CA1. However, to date, functional support for the existence of these subnetworks is available only for the CA1 and CA3 and whether spatial and non-spatial information are processed differently by the enclosed and exposed blades of the DG, remains unknown. In the present work, I show by combining behavioural, optogenetic, and molecular imaging approaches that the exposed blade of the DG is critical for non-spatial memory processing and is part of the non-spatial hippocampal subnetwork. In contrast, the enclosed blade of the DG preferentially supports spatial memory retrieval and interacts with both, spatial and non-spatial hippocampal subnetworks. Additionally, I present anatomical tracing data suggesting that the origin of cortical projections to the individual DG blades from the lateral and medial entorhinal cortices, which are differentially tuned to spatial/non-spatial processing, might give rise to the spatial/non-spatial double dissociation of the DG blades. Altogether, these data strongly support the claim that the DG blades are parts of distinct hippocampal subnetworks embedded in larger-scale medial temporal lobe subnetworks with selective functional ties to spatial and non-spatial information processing. These insights improve our knowledge about the neural circuits supporting episodic memories and will be helpful for future research aimed at preventing and rescuing memory deficits.