Adult born hippocampal granule cells promote pattern separation by bidirectionally modulating the remapping of place and cue cells

The hippocampal dentate gyrus (DG) exhibits a unique form of neural plasticity that results from continuous integration of adult born neurons, referred to as ‘adult neurogenesis’. Recent studies have proposed that adult neurogenesis promotes the ability to encode new memories without interference from previously stored memories that share similar features, through a neural computation known as pattern separation. However, due to lack of in vivo physiological evidence, the manner in which adult neurogenesis contributes to pattern separation remains unknown. Here, we investigate the contribution of functionally integrated yet immature adult born granule cells (iGCs) to DG computations by examining how chronic ablation or acute chemogenetic silencing of iGCs affects the activity of mature granule cells (mGCs) using in vivo 2-photon Ca 2+ imaging. In both cases we observed altered remapping of mGCs but in opposite directions depending on their tuning selectivity. Rather than broadly modulating the activity of all mGCs, iGCs promote the remapping of place cells but limit the remapping of mGCs representing sensory cues (cue cells). We propose that these properties of iGCs explain their role in pattern separation because they promote the formation of non-overlapping representations for identical sensory cues encountered in different locations. Conversely, the absence of iGCs shifts the DG network to a state dominated by sensory cue information, a situation that is consistent with the overgeneralization often observed in anxiety disorders such as PTSD.