Modulating neuronal competition dynamics in the dentate gyrus to rejuvenate aging memory circuits
Summary: 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 spin...
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| Hauptverfasser: | , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
September 1, 2016
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| In: |
Neuron
Year: 2016, Jahrgang: 91, Heft: 6, Pages: 1356-1373 |
| ISSN: | 1097-4199 |
| DOI: | 10.1016/j.neuron.2016.08.009 |
| Online-Zugang: | Verlag, Volltext: http://dx.doi.org/10.1016/j.neuron.2016.08.009 Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S0896627316305013 
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| Verfasserangaben: | Kathleen M. McAvoy, Kimberly N. Scobie, Stefan Berger, Craig Russo, Nannan Guo, Pakanat Decharatanachart, Hugo Vega-Ramirez, Sam Miake-Lye, Michael Whalen, Mark Nelson, Matteo Bergami, Dusan Bartsch, Rene Hen, Benedikt Berninger, and Amar Sahay |
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| 520 | |a Summary: 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. | ||
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