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首页> 外文期刊>Neurobiology of learning and memory >Role of adult neurogenesis in hippocampus-dependent memory, contextual fear extinction and remote contextual memory: New insights from ERK5 MAP kinase
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Role of adult neurogenesis in hippocampus-dependent memory, contextual fear extinction and remote contextual memory: New insights from ERK5 MAP kinase

机译：成人神经发生在海马依赖型记忆，语境恐惧消退和语境远程记忆中的作用：ERK5 MAP激酶的新见解

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Adult neurogenesis occurs in two discrete regions of the adult mammalian brain, the subgranular zone (SGZ) of the dentate gyrus (DG) and the subventricular zone (SVZ) along the lateral ventricles. Signaling mechanisms regulating adult neurogenesis in the SGZ are currently an active area of investigation. Adult-born neurons in the DG functionally integrate into the hippocampal circuitry and form functional synapses, suggesting a role for these neurons in hippocampus-dependent memory formation. Although results from earlier behavioral studies addressing this issue were inconsistent, recent advances in conditional gene targeting technology, viral injection and optogenetic approaches have provided convincing evidence supporting a role for adult-born neurons in the more challenging forms of hippocampus-dependent learning and memory. Here, we briefly summarize these recent studies with a focus on extra signal-regulated kinase (ERK) 5, a MAP kinase whose expression in the adult brain is restricted to the neurogenic regions including the SGZ and SVZ. We review evidence identifying ERK5 as a novel endogenous signaling pathway that regulates the pro-neural transcription factor Neurogenin 2, is activated by neurotrophins and is critical for adult neurogenesis. We discuss studies demonstrating that specific deletion of ERK5 in the adult neurogenic regions impairs several forms of hippocampus-dependent memory formation in mice. These include contextual fear memory extinction, the establishment and maintenance of remote contextual fear memory, and several other challenging forms of hippocampus-dependent memory formation including 48. h memory for novel object recognition, contextual fear memory established by a weak foot shock, pattern separation, and reversal of spatial learning and memory. We also briefly discuss current evidence that increasing adult neurogenesis, by small molecules or genetic manipulation, improves memory formation and long-term memory.
机译：成年神经发生发生在成年哺乳动物脑的两个离散区域，即齿状回（DG）的颗粒下区（SGZ）和沿侧脑室的脑室下区（SVZ）。 SGZ中调节成人神经发生的信号传导机制是目前研究的活跃领域。 DG中的成年神经元在功能上整合到海马回路中并形成功能性突触，表明这些神经元在海马依赖性记忆形成中发挥了作用。尽管针对此问题的早期行为研究的结果不一致，但条件基因靶向技术，病毒注射和光遗传学方法的最新进展提供了令人信服的证据，证明了成年出生的神经元在更具挑战性的海马依赖性学习和记忆形式中的作用。在这里，我们简要概述这些最新研究，重点是额外的信号调节激酶（ERK）5，即一种MAP激酶，其在成人大脑中的表达仅限于包括SGZ和SVZ在内的神经源性区域。我们审查的证据确定ERK5为新的内源性信号通路，调节前神经转录因子Neurogenin 2，由神经营养蛋白激活，对成人神经发生至关重要。我们讨论的研究表明，成年神经源性区域中ERK5的特异性缺失会损害小鼠海马依赖型记忆形成的几种形式。这些包括背景恐惧记忆的消亡，远程背景恐惧记忆的建立和维持，以及海马依赖记忆形成的其他几种具有挑战性的形式，包括48. h用于新型物体识别的记忆，通过弱足震动建立的背景恐惧记忆，模式分离，以及空间学习和记忆的逆转。我们还简要讨论了当前的证据，即通过小分子或遗传操作增加成人神经发生可改善记忆形成和长期记忆。

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