In Vivo Calcium Imaging at the Frontal Cortex in Mouse Models of Brain Disorders

神经科学的核心任务之一是了解神经元活动如何携带信息来指导行为。一种直接的方法是在动物自由执行行为任务的同时，在活体上同时记录大规模的神经活动。这种测量可以建立详细的机制，通过这些机制，单个神经元或神经集合的活动编码动物的行为。微型荧光显微镜（miniScope）的发展为获得自由行为小鼠的大规模活体神经钙成像开辟了新的途径，以阐明健康和疾病中神经回路的功能和功能障碍。拟议工作的长期目标是开发和应用尖端的miniScope成像技术来研究内侧前额叶皮层（mPFC）中抑郁症，自闭症和痴呆症的神经回路机制。该提案有以下两个具体目标：目标1。阐明mPFC神经回路功能障碍如何导致抑郁症、自闭症和痴呆症患者的社会行为缺陷。抑郁症、自闭症和痴呆症患者都表现出社会行为缺陷。为了揭示导致这些大脑疾病中社会行为缺陷的潜在回路机制，将采用miniScope成像方法来检查抑郁症，自闭症和额颞叶痴呆小鼠模型中的mPFC神经回路。目标#2：开发双色miniScopes以推进神经回路研究。将开发具有双LED和液体透镜的新版本的miniScope。这种新的miniScope不仅可以实现主神经元和抑制性中间神经元的双色钙成像，还可以实现中间神经元的光遗传学操作和主神经元的同步钙成像。

One of the core missions in neuroscience is to understand how neuronal activities carry information to guide behavior. A direct approach is to simultaneously record large-scale neural activity in vivo while animal freely performs behavioral tasks. Such measurement could establish detailed mechanisms by which activity of individual neurons or neural ensembles codes animal’s behavior. The development of miniature fluorescence microscope (miniScope) opens up new avenues for obtaining large-scale in vivo neural calcium imaging from freely behaving mice, to elucidate the function and dysfunction of neural circuitry in health and diseases. The long-term goal of the proposed work is to develop and to apply cutting-edge miniScope imaging technique to study neural circuit mechanisms of depression, autism, and dementia in the medial prefrontal cortex (mPFC). This proposal has the following two specific aims: Aim#1. To elucidate how dysfunctional mPFC neural circuits contribute to social behavior deficits in depression, autism, and dementia. Human patients of depression, autism, and dementia all display deficits in social behavior. To unravel the underlying circuit mechanisms leading to social behavior deficits in these brain disorders, miniScope imaging approach will be employed to examine mPFC neural circuitry in mouse models of depression, autism, and frontotemporal dementia. Aim#2: To develop dual-color miniScopes to advance neural circuitry studies. A new version of miniScope with dual LED and a liquid lens will be developed. This new miniScope will enable not only dual-color calcium imaging from both principle neurons and inhibitory interneurons, but also optogenetic manipulation of interneurons and concurrent calcium imaging from principle neurons.