Modulating Neuronal Competition Dynamics in the Dentate Gyrus to Rejuvenate Aging Memory Circuits.
| Authors | |
| Abstract | The neural circuit mechanisms underlying the integration and functions of adult-born dentate granule cell (DGCs) are poorly understood. Adult-born DGCs are thought to compete with mature DGCs for inputs to integrate. Transient genetic overexpression of a negative regulator of dendritic spines, Kruppel-like factor 9 (Klf9), in mature DGCs enhanced integration of adult-born DGCs and increased NSC activation. Reversal of Klf9 overexpression in mature DGCs restored spines and activity and reset neuronal competition dynamics and NSC activation, leaving the DG modified by a functionally integrated, expanded cohort of age-matched adult-born DGCs. Spine elimination by inducible deletion of Rac1 in mature DGCs increased survival of adult-born DGCs without affecting proliferation or DGC activity. Enhanced integration of adult-born DGCs transiently reorganized adult-born DGC local afferent connectivity and promoted global remapping in the DG. Rejuvenation of the DG by enhancing integration of adult-born DGCs in adulthood, middle age, and aging enhanced memory precision. |
| Year of Publication | 2016
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| Journal | Neuron
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| Volume | 91
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| Issue | 6
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| Pages | 1356-73
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| Date Published | 2016 Sep 21
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| ISSN | 1097-4199
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| DOI | 10.1016/j.neuron.2016.08.009
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| PubMed ID | 27593178
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| PubMed Central ID | PMC5033725
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| Links | |
| Grant list | R01 MH104175 / MH / NIMH NIH HHS / United States
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