ERK5 in Learning and Memory

描述（由申请人提供）：学习和记忆缺陷是许多精神障碍的突出特征。了解负责学习和记忆的分子机制是开发改善精神疾病治疗中学习和记忆的疗法的关键。最近的研究提出了一个令人兴奋的想法，即海马成年齿状回（DG）中新生成的神经元可能在包括海马依赖性记忆形成在内的神经可塑性中发挥作用。成人神经发生发生在哺乳动物大脑的DG中，包括在生理条件下的成人大脑，新生成的神经元在功能上与DG整合。包括抑郁和其他精神疾病在内的许多因素可能对海马成年神经发生产生不利影响。相比之下，抗抑郁药物治疗和运动是治疗抑郁症的有效手段，可增强成人DG中的神经发生。因此，阐明调节成人海马神经发生的基本分子机制和提供明确证据支持成人神经发生在海马依赖记忆形成中的作用，是心理健康研究的一个关键和及时的问题。尽管许多研究已经评估了成人神经发生在海马依赖性学习和记忆中的作用，但结果并不一致，这使得成人神经发生是否有助于海马依赖性记忆的形成仍然存在高度争议。这一提议将验证ERK5信号介导的成人神经发生在一些但不是所有形式的海马依赖学习和记忆中起关键作用的假设。

DESCRIPTION (provided by applicant): Deficits in learning and memory are prominent features of many mental disorders. Understanding molecular mechanisms responsible for learning and memory are key to the development of therapies to improve learning and memory in the treatment of mental illness. Recent studies lead to the exciting idea that newly generated neurons in the adult dentate gyrus (DG) of the hippocampus may play a role in neural plasticity including hippocampal-dependent memory formation. Adult neurogenesis occurs in the DG of the mammalian brains including adult human brain under physiological conditions and newly generated neurons functionally integrate to the DG. Many factors, including depression and other mental illness may adversely affect hippocampal adult neurogenesis. In contrast, treatment with anti-depressants and exercise, an effective means to treat depression, enhance adult neurogenesis in the DG. Consequently, elucidation of basic molecular mechanisms regulating adult hippocampal neurogenesis and generation of definitive evidence supporting a role for adult neurogenesis in hippocampal-dependent memory formation is a critical and timely issue for mental health research. Although many studies have assessed the role of adult neurogenesis in hippocampal-dependent learning and memory, the results have been inconsistent, making it still highly controversial whether adult neurogenesis contributes to hippocampus-dependent memory formation. This proposal will test the hypothesis that ERK5 signaling-mediated adult neurogenesis plays a critical role in some but not all forms of hippocampal- dependent learning and memory. PUBLIC HEALTH RELEVANCE: Our proposed studies are likely to provide new insights concerning signal transduction mechanisms regulating adult neurogenesis, and may lead to new insights to the development of therapies to improve learning and memory in the treatment of mental illness.