A sparse, spatially biased subtype of mature granule cell is preferentially recruited in hippocampal-associated behaviors

ABSTRACT 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 found that a broad range of novel experiences preferentially activates granule cells of the suprapyramidal blade relative to the infrapyramidal blade. Motivated by this, we identified a suprapyramidal-blade-enriched population of granule cells with distinct spatial, morphological, physiological, and developmental properties. Via transcriptomics, we mapped these traits onto a sparse and discrete granule cell subtype that was recruited at a ten-fold greater frequency than expected by subtype prevalence, constituting the majority of all recruited granule cells. Thus, a rare and spatially localized granule cell subtype is intrinsically predisposed to activation during hippocampal memory formation.