Analysis of the role of hippocampal adult-born neurons in behavior and physiology

描述（由申请人提供）：该项目的主要目标是确定成人海马神经发生在海马依赖性学习和记忆中的参与。研究表明，海马的齿状回有能力在成年后产生新的神经元。这些新生细胞中的许多成熟为具有功能性突触的齿状颗粒神经元。先前的文献表明，啮齿动物海马神经发生的消融抑制了抗抑郁药物的行为反应，并导致了神经发生是抗抑郁药物治疗作用所必需的假设。相反，神经发生的停滞会损害几种形式的依赖于大脑皮层的学习。我们已经证明，使用x射线照射或诱导基因消融方法阻断海马神经发生会损害背景恐惧条件反射，但会改善工作记忆任务，即新物体识别。此外，使用这些方法阻止神经发生消除了内侧穿支通路中的长时程电位（LTP）形式，称为ACSF-LTP。考虑到发育中的成年出生的神经元表现出独特的生理特性的证据，拟议的研究将使用上下文恐惧条件反射，新物体识别和电生理学（ACSF-LTP）来确定在什么年龄成年出生的神经元成为这些依赖于大脑的任务所必需的。 公共卫生相关性：海马神经发生已被证明会影响特定的学习模式以及抗抑郁反应。旨在刺激海马神经发生的策略可以为认知和情绪障碍的治疗提供新的途径。

DESCRIPTION (provided by applicant): The broad goal of this project is to determine the involvement of adult hippocampal neurogenesis in hippocampal-dependent learning and memory. It has been shown that the dentate gyrus of the hippocampus has the ability to produce new neurons into adulthood. Many of these newborn cells mature into dentate granule neurons with functional synapses. Previous literature showed that ablation of hippocampal neurogenesis in rodents inhibits the behavioral response to antidepressant drugs and led to the hypothesis that neurogenesis is required for the therapeutic action of antidepressant drugs. Conversely, arresting neurogenesis impairs several forms of hippocampus-dependent learning. We have shown that blocking hippocampal neurogenesis using x-irradiation or an inducible genetic ablation method impairs contextual fear conditioning but improves a working memory task, novel object recognition. Furthermore, arrest of neurogenesis using these methods eliminates a form of long term potentiatioh (LTP) in the medial perforant path, termed ACSF-LTP. In consideration of evidence that developing adult-born neurons exhibit unique physiological properties, the proposed research will use contextual fear conditioning, novel object recognition, and electrophysiology (ACSF-LTP) to determine at what age adult-bom neurons become necessary for these hippocampal-dependent tasks. PUBLIC HEALTH RELEVANCE: Hippocampal neurogenesis has been shown to influence specific learning paradigms as well as antidepressant responses. Strategies aimed at stimulating hippocampal neurogenesis could provide novel avenues for the treatment of cognitive and mood disorders.