A Sparse, Spatially Biased Subtype of Mature Granule Cell Dominates Recruitment in Hippocampal-Associated Behaviors

Abstract

Summary: Animals can store information about experiences by activating specific neuronal populations, and subsequent reactivation of these neural ensembles can lead to recall of salient experiences. In the hippocampus, granule cells of the dentate gyrus participate in such memory engrams; however, whether there is an underlying logic to granule cell participation has not been examined. Here, we find that a range of novel experiences preferentially activates granule cells of the suprapyramidal blade relative to the infrapyramidal blade. Motivated by this, we identify a suprapyramidal-blade-enriched population of granule cells with distinct spatial, morphological, physiological, and developmental properties. Via transcriptomics, we map these traits onto a sparse and discrete granule cell subtype that is recruited at a 10-fold greater frequency than expected by subtype prevalence, constituting the majority of all recruited granule cells. Thus, in behaviors known to involve hippocampal-dependent memory formation, a rare and spatially localized subtype dominates overall granule cell recruitment. : Erwin et al. identify a sparse subtype of mature granule cell, spatially localized within the dentate gyrus, which dominates overall granule cell activity across a range of behavioral paradigms. Thus, subtype-specific heterogeneity exists and predicts cellular recruitment at the first stage of hippocampal processing. Keywords: dentate gyrus, granule cell, single-cell RNA-seq, transcriptomics, memory, cell type, hippocampus