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: 10214047
• 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
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10214047
• 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以指导行为。一种直接的方法是简单地记录体内大规模的神经元活动，而动物无动物执行行为任务。这样的测量可以建立详细的机制，通过这种机制，单个神经元或神经元合奏代码的活性可以建立动物的行为。微型荧光显微镜（Miniscope）的发展开辟了新的途径，用于从自由行为的小鼠中获得大规模的体内神经元成像，以阐明健康和疾病中神经元电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，自闭症和痴呆症的神经元回路机制。该提案具有以下两个具体目标：目标＃1。为了阐明功能失调的MPFC神经元电路如何导致抑郁症，自闭症和痴呆症的社会行为缺陷。抑郁，自闭症和痴呆症患者的人类患者都在社会行为中显示出定义。为了揭示导致这些脑部疾病中社会行为缺陷的潜在电路机制，将采用Miniscope成像方法来检查抑郁症，自闭症和额颞痴呆的小鼠模型中的MPFC神经元电路。目标＃2：开发双色米斯科植物以推进神经元回路研究。将开发带有双LED和液态镜头的新版本的Miniscope。这种新的Miniscope不仅可以使来自原理神经元和抑制​​性神经元的双色钙成像，还可以对原理神经元的中间神经元和同时钙成像进行光学遗传操纵。