Journal
NEUROTHERAPEUTICS
Volume 14, Issue 3, Pages 630-645Publisher
SPRINGER
DOI: 10.1007/s13311-017-0539-6
Keywords
Aging; Neurogenesis; Dentate gyrus; Hippocampus; Memory; Pattern separation
Funding
- US National Institutes of Health Biobehavioral Research Awards for Innovative New Scientists (BRAINS) [1-R01MH104175]
- NIH-NIA [1R01AG048908-01A1]
- NARSAD Independent Investigator Award
- Ellison Medical Foundation New Scholar in Aging
- Whitehall Foundation
- Inscopix Decode award
- Ellison Family Philanthropic support
- Harvard Neurodiscovery Center/MADRC Center Pilot Grant Award
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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.
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