Adult-born hippocampal neurons promote cognitive flexibility in mice

被引:233
作者
Burghardt, Nesha S. [2 ,3 ,4 ]
Park, Eun Hye [1 ,5 ]
Hen, Rene [2 ,3 ,4 ]
Fenton, Andre A. [1 ,5 ]
机构
[1] NYU, Ctr Neural Sci, New York, NY 10003 USA
[2] Columbia Univ, Dept Neurosci, New York, NY USA
[3] Columbia Univ, Dept Neurosci & Psychiat, New York, NY USA
[4] New York State Psychiat Inst & Hosp, Div Integrat Neurosci, New York, NY 10032 USA
[5] Suny Downstate Med Ctr, Robert F Furchgott Ctr Neural & Behav Sci, Dept Physiol & Pharmacol, Brooklyn, NY 11203 USA
关键词
neurogenesis; hippocampus; dentate gyrus; activity-regulated cytoskeleton-associated protein (Arc); active place avoidance; ENHANCED SYNAPTIC PLASTICITY; GENERATED GRANULE CELLS; LONG-TERM POTENTIATION; DENTATE GYRUS; SPATIAL MEMORY; BEHAVIORAL EVIDENCE; STRESS RESPONSES; RAT HIPPOCAMPUS; CRITICAL PERIOD; NEUROGENESIS;
D O I
10.1002/hipo.22013
中图分类号
Q189 [神经科学];
学科分类号
071006 [神经生物学];
摘要
The hippocampus is involved in segregating memories, an ability that utilizes the neural process of pattern separation and allows for cognitive flexibility. We evaluated a proposed role for adult hippocampal neurogenesis in cognitive flexibility using variants of the active place avoidance task and two independent methods of ablating adult-born neurons, focal X-irradiation of the hippocampus, and genetic ablation of glial fibrillary acidic protein positive neural progenitor cells, in mice. We found that ablation of adult neurogenesis did not impair the ability to learn the initial location of a shock zone. However, when conflict was introduced by switching the location of the shock zone to the opposite side of the room, irradiated and transgenic mice entered the new shock zone location significantly more than their respective controls. This impairment was associated with increased upregulation of the immediate early gene Arc in the dorsal dentate gyrus, suggesting a role for adult neurogenesis in modulating network excitability and/or synaptic plasticity. Additional experiments revealed that irradiated mice were also impaired in learning to avoid a rotating shock zone when it was added to an initially learned stationary shock zone, but were unimpaired in learning the identical simultaneous task variant if it was their initial experience with place avoidance. Impaired avoidance could not be attributed to a deficit in extinction or an inability to learn a new shock zone location in a different environment. Together these results demonstrate that adult neurogenesis contributes to cognitive flexibility when it requires changing a learned response to a stimulus-evoked memory. (c) 2012 Wiley Periodicals, Inc.
引用
收藏
页码:1795 / 1808
页数:14
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