Imaging adult-born neurons in action using head-mounted minimicroscopes

项目摘要/摘要 海马体是少数几个在成年后保留产生神经元能力的大脑区域之一。 对人类患者和动物模型的研究表明，神经发生的增加和减少会改变 记忆功能，并对情绪障碍的病因和治疗做出贡献。尽管快15年了 在将成人神经发生与记忆和情绪调节联系起来的研究中，几乎对 成年神经发生影响这些过程的回路和编码机制。最近的 头戴式微型显微镜的开发(在大脑倡议的支持下)提供了前所未有的 当动物学习和行为时，有机会想象成年出生神经元的活动。在这个奖项下，我们将 获取设备和培训，使我们的实验室能够可持续地将迷你望远镜成像整合到我们的 成人神经发生研究计划。此外，我们还将在Free中进行钙成像实验 老鼠在探索情境和经历情境恐惧条件反射时移动，这是一种学习模式 这对成人神经发生的扰动很敏感。利用成年出生的神经元的光遗传沉默，我们 将描述成年出生的神经元如何影响齿状回这一区域的上下文记忆编码 上下文存储所需的。这些实验将提供以前无法获得的新见解 成年神经元调节海马体记忆的机制，它们将使我们的实验室能够 以可持续的方式将迷你望远镜技术整合到多个正在进行的研究流中。

Project Summary/Abstract The hippocampus is one of a select few brain regions that retain the ability to generate neurons in adulthood. Research in human patients and animal models suggests that increases and decreases in neurogenesis alter memory function and contribute to the etiology and treatment of emotional disorders. Despite almost 15 years of research linking adult neurogenesis to memory and emotional regulation, almost nothing is known about the circuit and coding mechanisms through which adult neurogenesis influences these processes. The recent development (with BRAIN Initiative support) of head-mounted minimicroscopes provides an unprecedented opportunity to image activity of adult-born neurons as animals learn and behave. Under this award, we will acquire equipment and training that will enable our lab to sustainably incorporate miniscope imaging into our research program on adult neurogenesis. In addition, we will perform calcium imaging experiments in freely moving mice as they explore contexts and undergo contextual fear conditioning, a model learning paradigm that is sensitive to perturbations of adult neurogenesis. Using optogenetic silencing of adult-born neurons, we will characterize how adult-born neurons influence coding of context memory in dentate gyrus, a region required for context memory. These experiments will provide new and previously unattainable insights into the mechanisms through which adult-born neurons regulate hippocampal memory, and they will enable our lab to integrate miniscope technology in a sustainable way in multiple ongoing research streams.