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Molecular mechanisms underlying the functional integration of adult-born hippocampal neurons - implications for depression and anxiety.

机译:成年海马神经元功能整合的分子机制-对抑郁和焦虑的影响。

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摘要

The hippocampus is one of two regions in the adult mammalian brain that continues to generate new neurons in adulthood and throughout life. Despite the small number of new neurons generated, they contribute enhanced hippocampal long-term potentiation and are necessary for certain forms of animal behavior such as contextual fear learning and behavioral response to antidepressant treatments. This thesis discusses how antidepressant treatments and neurotrophic factors influence the functional integration of adult-born hippocampal neurons, and in turn impact behavior. Specifically, chronic antidepressant treatment accelerates the maturation of newborn neurons and stimulates a form of hippocampal long-term potentiation that is dependent upon neurogenesis. In addition, cell-autonomous TrkB signaling in adult progenitors and newborn neurons influences the long-term survival of new neurons, their ability to exhibit long-term plasticity, animal behavior in contextual fear conditioning and anxiety-like behavior in response to stress. Furthermore, cell-autonomous TrkB signaling in adult progenitors and newborn neurons mediates the antidepressant-induced acceleration of maturation and enhanced survival of new neurons. Overall, these findings offer insight into how functional integration of adult-born hippocampal neurons influences an animal's behavior, and may uncover ways to develop better and faster acting antidepressant treatments.
机译:海马是成年哺乳动物脑中两个区域之一,该区域在成年期和整个生命过程中继续产生新的神经元。尽管生成的新神经元数量很少,但它们有助于增强海马的长期增强能力,对于某些形式的动物行为(如情境恐惧学习和对抗抑郁药的行为反应)是必需的。本文讨论了抗抑郁药治疗和神经营养因子如何影响成年海马神经元的功能整合,进而影响行为。具体而言,慢性抗抑郁药治疗可加速新生儿神经元的成熟,并刺激依赖于神经发生的海马长期增强形式。此外,成年祖细胞和新生神经元中的细胞自主性TrkB信号传导会影响新神经元的长期存活,它们表现出长期可塑性的能力,在情境恐惧条件下的动物行为以及对应激的焦虑样行为。此外,成年祖细胞和新生神经元中的细胞自主性TrkB信号传导介导抗抑郁药诱导的成熟加速和新神经元存活率的提高。总体而言,这些发现提供了关于成年海马神经元功能整合如何影响动物行为的见识,并可能揭示开发更好,更快速地发挥作用的抗抑郁治疗方法。

著录项

  • 作者

    Wang, Jingwen.;

  • 作者单位

    Columbia University.;

  • 授予单位 Columbia University.;
  • 学科 Biology Molecular.;Biology Physiology.;Biology Neuroscience.
  • 学位 Ph.D.
  • 年度 2009
  • 页码 147 p.
  • 总页数 147
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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