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

脑部疾病小鼠模型额叶皮层的体内钙成像

• 批准号: 10216279
• 负责人: YUN LI
• 金额: $ 17.66万
• 依托单位: UNIVERSITY OF WYOMING
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10216279
• 关键词: Animal Behavior; Animals; Behavior; Behavioral; Biology; Brain Diseases; Calcium; Centers of Research Excellence; Code; Color; Dementia; Development; Disease; Frontotemporal Dementia; Goals; Health; Human; Image; Imaging Techniques; Individual; Interneurons; Liquid substance; Measurement; Medial; Mental Depression; Mission; Mus; Neuronal Dysfunction; Neurons; Neurosciences; Patients; Prefrontal Cortex; Sensory; Social Behavior; Work; Wyoming; autism spectrum disorder; depression model; fluorescence microscope; frontal lobe; imaging approach; in vivo; in vivo calcium imaging; lens; mouse model; neural circuit; optogenetics; relating to nervous system

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.

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记录体内大规模的神经活动。这种测量可以建立详细的机制，通过这些机制，单个神经元或神经群的活动编码动物的行为。微型荧光显微镜（miniScope）的发展开辟了从自由行为的小鼠身上获得大规模体内神经钙成像的新途径，以阐明神经回路在健康和疾病中的功能和功能障碍。该工作的长期目标是开发并应用尖端的微型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。阐明功能失调的 mPFC 神经回路如何导致抑郁症、自闭症和痴呆症的社会行为缺陷。人类抑郁症、自闭症和痴呆症患者都表现出社交行为缺陷。为了揭示导致这些大脑疾病社会行为缺陷的潜在回路机制，将采用 miniScope 成像方法检查抑郁症、自闭症和额颞叶痴呆小鼠模型中的 mPFC 神经回路。目标#2：开发双色迷你显微镜以推进神经回路研究。将开发带有双 LED 和液体透镜的新版本 miniScope。这种新的迷你显微镜不仅可以实现主要神经元和抑制​​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要神经元的并发钙成像。