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首页> 外文期刊>Nature >Hippocampal neurogenesis confers stress resilience by inhibiting the ventral dentate gyrus
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Hippocampal neurogenesis confers stress resilience by inhibiting the ventral dentate gyrus

机译：海马神经发生通过抑制腹侧齿状回赋予应激弹性

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摘要

Adult neurogenesis in the dentate gyrus of the hippocampus is highly regulated by environmental influences, and functionally implicated in behavioural responses to stress and antidepressants(1-4). However, how adult-born neurons regulate dentate gyrus information processing to protect from stress-induced anxiety-like behaviour is unknown. Here we show in mice that neurogenesis confers resilience to chronic stress by inhibiting the activity of mature granule cells in the ventral dentate gyrus (vDG), a subregion that is implicated in mood regulation. We found that chemogenetic inhibition of adult-born neurons in the vDG promotes susceptibility to social defeat stress, whereas increasing neurogenesis confers resilience to chronic stress. By using in vivo calcium 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 whereas 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.
机译：海马齿状回中的成年神经发生受到环境影响的高度调节，并在功能上牵涉对应激和抗抑郁药的行为反应（1-4）。然而，成年神经元如何调节齿状回信息处理以保护免受应激诱导的焦虑样行为的影响尚不清楚。在这里，我们在小鼠中显示，神经发生通过抑制腹侧齿状回（vDG）（涉及情绪调节的一个子区域）中的成熟颗粒细胞的活性，赋予了慢性应激适应能力。我们发现vDG中成人出生的神经元的化学发生抑制作用促进了对社交失败压力的敏感性，而增加的神经发生赋予了对慢性压力的适应力。通过使用体内钙显像来记录vDG中大型细胞群体的神经元活性，我们显示神经发生增加导致应激反应性细胞的活性降低，应激反应性细胞在攻击过程中或小鼠探索焦虑发生环境时优先活跃。这些对齿状回活动的影响对于应力弹性是必要的，并且是足够的，因为vDG的直接沉默赋予弹性，而激发促进敏感性。我们的结果表明，vDG的活性可能是确定个体对压力和相关精神疾病的脆弱性水平的关键因素。

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  • 来源
    《Nature》 |2018年第7712期|98-102|共5页
  • 作者

    Anacker Christoph; Luna Victor M.; Stevens Gregory S.; Millette Amira; Shores Ryan; Jimenez Jessica C.; Chen Briana; Hen Rene;

  • 作者单位

    Columbia Univ, Dept Psychiat, Div Syst Neurosci, New York, NY 10027 USA;

    Columbia Univ, Dept Psychiat, Div Syst Neurosci, New York, NY 10027 USA;

    Columbia Univ, Dept Psychiat, Div Syst Neurosci, New York, NY 10027 USA;

    Columbia Univ, Dept Psychiat, Div Syst Neurosci, New York, NY 10027 USA;

    Columbia Univ, Dept Psychiat, Div Syst Neurosci, New York, NY 10027 USA;

    Columbia Univ, Dept Psychiat, Div Syst Neurosci, New York, NY 10027 USA;

    Columbia Univ, Dept Psychiat, Div Syst Neurosci, New York, NY 10027 USA;

    Columbia Univ, Dept Psychiat, Div Syst Neurosci, New York, NY 10027 USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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