Hippocampal neurogenesis confers stress resilience by inhibiting the ventral dentate gyrus.
Hippocampal neurogenesis confers stress resilience by inhibiting the ventral dentate gyrus.
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DOI：
10.1038/s41586-018-0262-4
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发表时间：
2018-07
期刊：
影响因子：
64.8
通讯作者：
Hen R
中科院分区：
文献类型：
--
作者：
Anacker C;Luna VM;Stevens GS;Millette A;Shores R;Jimenez JC;Chen B;Hen R
成年人海马齿状回的神经发生受到环境影响的高度调节，并在功能上与对压力和抗抑郁药的行为反应有关。然而，成人出生的神经元如何调节齿状回信息处理以防止压力诱导的焦虑样行为尚不清楚。在这里，我们表明，神经发生赋予弹性的慢性压力，通过抑制腹侧齿状回（vDG），一个亚区参与情绪调节的成熟颗粒细胞的活动。我们发现，成人出生的神经元在vDG的化学发生抑制促进社会失败压力的易感性，而增加神经发生赋予慢性压力的弹性。使用体内钙（Ca2+）成像记录神经元活动从大细胞群体中的vDG，我们发现，增加神经发生的结果在减少的活动中的“应激反应细胞”，优先在攻击或小鼠探索焦虑的环境中活跃。这些对齿状回活动的影响是必要的，足够的压力弹性，直接沉默的vDG赋予弹性，而兴奋促进易感性。我们的研究结果表明，活性的vDG可能是一个关键因素，在确定个人的脆弱性水平的压力和相关的精神疾病。
Adult neurogenesis in the dentate gyrus of the hippocampus is highly regulated by environmental influences, and functionally implicated in behavioral responses to stress and antidepressants. However, how adult-born neurons regulate dentate gyrus information processing to protect from stress-induced anxiety-like behavior is unknown. Here we show that neurogenesis confers resilience to chronic stress by inhibiting the activity of mature granule cells in the ventral dentate gyrus (vDG), a subregion implicated in mood regulation. We found that chemogenetic inhibition of adult-born neurons in the vDG promotes susceptibility to social defeat stress while increasing neurogenesis confers resilience to chronic stress. Using in vivo calcium (Ca2+) imaging to record neuronal activity from large cell populations in the vDG, we show that increased neurogenesis results in a decrease in the activity of “stress-responsive cells” that are active preferentially during attacks or while mice explore anxiogenic environments. These effects on dentate gyrus activity are necessary and sufficient for stress resilience, as direct silencing of the vDG confers resilience, while excitation promotes susceptibility. Our results suggest that the activity of the vDG may be a key factor in determining individual levels of vulnerability to stress and related psychiatric disorders.
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影响因子：
3.7
作者：
Mongiat LA;Espósito MS;Lombardi G;Schinder AF
通讯作者：
Schinder AF
影响因子：
56.9
作者：
Santarelli, L;Saxe, M;Hen, R
通讯作者：
Hen, R
影响因子：
16.2
作者：
Padilla-Coreano N;Bolkan SS;Pierce GM;Blackman DR;Hardin WD;Garcia-Garcia AL;Spellman TJ;Gordon JA
通讯作者：
Gordon JA
DOI：
10.1126/science.1205295
发表时间：
2011-07-29
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Ray RS;Corcoran AE;Brust RD;Kim JC;Richerson GB;Nattie E;Dymecki SM
通讯作者：
Dymecki SM
影响因子：
14.8
作者：
Resendez SL;Jennings JH;Ung RL;Namboodiri VM;Zhou ZC;Otis JM;Nomura H;McHenry JA;Kosyk O;Stuber GD
通讯作者：
Stuber GD