调节齿状回中的神经元竞争动态以恢复老化的记忆回路。
Modulating Neuronal Competition Dynamics in the Dentate Gyrus to Rejuvenate Aging Memory Circuits.
作者信息
McAvoy Kathleen M, Scobie Kimberly N, Berger Stefan, Russo Craig, Guo Nannan, Decharatanachart Pakanat, Vega-Ramirez Hugo, Miake-Lye Sam, Whalen Michael, Nelson Mark, Bergami Matteo, Bartsch Dusan, Hen Rene, Berninger Benedikt, Sahay Amar
机构信息
Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 USA.
Departments of Neuroscience and Psychiatry, Columbia University, New York, NY 10032, USA.
出版信息
Neuron. 2016 Sep 21;91(6):1356-1373. doi: 10.1016/j.neuron.2016.08.009. Epub 2016 Sep 1.
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.
成体新生齿状颗粒细胞（DGCs）整合及功能背后的神经回路机制目前仍知之甚少。成体新生DGCs被认为会与成熟DGCs竞争输入以进行整合。在成熟DGCs中瞬时基因过表达树突棘的负调节因子克鲁ppel样因子9（Klf9），可增强成体新生DGCs的整合并增加神经干细胞（NSC）的激活。在成熟DGCs中逆转Klf9过表达可恢复树突棘和活性，并重置神经元竞争动态及NSC激活，使齿状回被一群功能整合、数量增加的年龄匹配成体新生DGCs所修饰。通过在成熟DGCs中诱导性缺失Rac1来消除树突棘，可增加成体新生DGCs的存活率，而不影响其增殖或DGC活性。增强成体新生DGCs的整合会短暂重组成体新生DGC局部传入连接，并促进齿状回中的全局重映射。在成年期、中年期和衰老期通过增强成体新生DGCs的整合来使齿状回恢复活力，可提高记忆精度。
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