, Volume 14, Issue 3, pp 630–645 | Cite as

Targeting Adult Neurogenesis to Optimize Hippocampal Circuits in Aging



Millions of individuals suffer from age-related cognitive decline, defined by impaired memory precision. Increased understanding of hippocampal circuit mechanisms underlying memory formation suggests a role for computational processes such as pattern separation and pattern completion in memory precision. We describe evidence implicating the dentate gyrus-CA3 circuit in pattern separation and completion, and examine alterations in dentate gyrus-CA3 circuit structure and function with aging. We discuss the role of adult hippocampal neurogenesis in memory precision in adulthood and aging, as well as the circuit mechanisms underlying the integration and encoding functions of adult-born dentate granule cells. We posit that understanding these circuit mechanisms will permit generation of circuit-based endophenotypes that will edify new therapeutic strategies to optimize hippocampal encoding during aging.


Aging Neurogenesis Dentate gyrus Hippocampus Memory Pattern separation 



We thank members of the Sahay laboratory for their comments on the manuscript. A.S acknowledges grant support from US National Institutes of Health Biobehavioral Research Awards for Innovative New Scientists (BRAINS) 1-R01MH104175, NIH-NIA 1R01AG048908-01A1, 2017 NARSAD Independent Investigator Award, Ellison Medical Foundation New Scholar in Aging, Whitehall Foundation, Inscopix Decode award, Ellison Family Philanthropic support, and Harvard Neurodiscovery Center/MADRC Center Pilot Grant Award.


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Copyright information

© The American Society for Experimental NeuroTherapeutics, Inc. 2017

Authors and Affiliations

  1. 1.Center for Regenerative MedicineMassachusetts General HospitalBostonUSA
  2. 2.Harvard Stem Cell InstituteCambridgeUSA
  3. 3.Department of PsychiatryMassachusetts General Hospital, Harvard Medical SchoolBostonUSA
  4. 4.BROAD Institute of Harvard and MITCambridgeUSA

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