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

项目总结/摘要 海马体是少数几个在成年后仍能产生神经元的大脑区域之一。 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改变了 记忆功能，并有助于情绪障碍的病因和治疗。尽管在过去的15年里 关于成人神经发生与记忆和情绪调节之间的联系的研究，几乎没有什么是已知的。 回路和编码机制，通过成年神经发生影响这些过程。近期 头戴式微型显微镜的开发（在BRAIN Initiative的支持下）提供了前所未有的 有机会在动物学习和行为时成像成年出生的神经元的活动。在这个奖项下，我们将 获得设备和培训，使我们的实验室能够可持续地将微型成像纳入我们的 成人神经发生的研究项目此外，我们还将在免费的实验室进行钙成像实验。 移动老鼠，因为他们探索的背景和经历的背景恐惧条件反射，一个模型学习范式 对成人神经发生的扰动很敏感。利用成年神经元的光遗传学沉默，我们 将描述成年出生的神经元如何影响齿状回（一个区域）的上下文记忆编码。 需要上下文记忆。这些实验将提供新的和以前无法实现的见解， 成年神经元调节海马记忆的机制，它们将使我们的实验室能够 在多个正在进行的研究流中以可持续的方式整合微型望远镜技术。

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.