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. Author manuscript; available in PMC: 2020 Aug 3.
Published in final edited form as: Nat Neurosci. 2019 Sep 2;22(10):1565–1575. doi: 10.1038/s41593-019-0484-2

Fig. 3 ∣. Proposed role of adult-born DGCs in indexing and pattern separation.

Fig. 3 ∣

a, Refinement of abDGC input specificity during the sensitive period. Immature abDGCs (orange) mature into abDGCs (red) with high input-selectivity and respond to specific features experienced during the sensitive period (here only stimulus 2 of stimuli 0–3). b, Schematic of indexing. Overlapping experiences (A and B) are encoded in distinct engrams (or ‘indexes’) in the hippocampus (green). These indexes are linked to detailed representations of A and B that are distributed in downstream cortical and subcortical regions (yellow), much like the way a library index card corresponds to a book on the shelves of the library. c, Experiences A (blue) and B (yellow) represented by unique permutations of inputs (examples: 0–9) in association sensory cortices are relayed to the EC. A and B are transformed into distinct non-overlapping engrams or indexes in the DG through decorrelation of EC inputs in the DG, where inhibitory microcircuits sparsify DG activity through a winner-take-all circuit motif. Different combinations of mature abDGCs (outlined in black) are flexibly allocated into each engram (or index), with shared features recruiting the same DGCs (here: features 0 and 1). Feature-responsive DGCs (yellow and blue) inhibit neighboring DGCs (gray) to further refine the engram through the winner-take-all mechanism. Immature, <6-week-old abDGCs (outlined in yellow) encode novel features of B (here features 6 and 7) and contribute to the index of B while also exerting lateral inhibition. DGC recruitment of feedforward inhibition onto CA3 facilitates the transfer of the ensemble onto non-overlapping pyramidal cells in CA3 (triangles). The balance between DG and EC inputs in CA3 dictates whether pattern completion or separation occurs. The DG–CA3 engram represents an index of the memory, but does not encode all of its features; these are instead stored in the corresponding linked cortical traces (yellow and black squares). Activation of the index in DG–CA3 reinstates the cortical memory trace through pattern completion to mediate retrieval.