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Functions of adult-born neurons in hippocampal memory interference and indexing

Abstract

The dentate gyrus–CA3 circuit of the hippocampus is continuously modified by the integration of adult-born dentate granule cells (abDGCs). All abDGCs undergo a prolonged period of maturation, during which they exhibit heightened synaptic plasticity and refinement of electrophysiological properties and connectivity. Consistent with theoretical models and the known functions of the dentate gyrus–CA3 circuit, acute or chronic manipulations of abDGCs support a role for abDGCs in the regulation of memory interference. In this Review, we integrate insights from studies that examine the maturation of abDGCs and their integration into the circuit with network mechanisms that support memory discrimination, consolidation and clearance. We propose that adult hippocampal neurogenesis enables the generation of a library of experiences, each registered in mature abDGC physiology and connectivity. Mature abDGCs recruit inhibitory microcircuits to support pattern separation and memory indexing.

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Fig. 1: Development, experience and maturation of adult-born DGCs.
Fig. 2: Adult-born DGCs reduce memory interference and promote consolidation through inhibitory microcircuits.
Fig. 3: Proposed role of adult-born DGCs in indexing and pattern separation.

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Acknowledgements

We thank members of Sahay lab for discussions and L.M.S. Sahay for help with manuscript editing. A.S. acknowledges support from NIH-R01MH104175, NIH–R01AG048908, NIH-1R01MH111729, the James and Audrey Foster MGH Research Scholar Award, the Ellison Medical Foundation New Scholar in Aging, the Whitehall Foundation, an Inscopix Decode award, a NARSAD Independent Investigator Award, Ellison Family Philanthropic support, the Blue Guitar Fund, a Harvard Neurodiscovery Center–MADRC Center Pilot Grant award, Alzheimer’s Association Research Grant, a Harvard Stem Cell Institute Development grant, and an HSCI seed grant. The authors apologize to scientists whose works could not be cited due to limits on the number of references.

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Miller, S.M., Sahay, A. Functions of adult-born neurons in hippocampal memory interference and indexing. Nat Neurosci 22, 1565–1575 (2019). https://doi.org/10.1038/s41593-019-0484-2

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