Millisecond-Timescale Whole-Brain Neural Activity Mapping in Health and Disease

描述(由申请人提供)： 神经科学中的一大挑战是了解大脑中的神经元是如何作为一个电路一起工作来计算行为的，以及这种电路功能在大脑紊乱状态下是如何改变的。我们非常需要能够在哺乳动物(如老鼠)的大脑中测量大量单个细胞的神经活动的技术--理想情况下是整个大脑，因为我们不能准确地知道参与任何行为或大脑紊乱的确切细胞集。我们在这里提出了两项与过去截然不同的建议，使用计算和理论分析来设计新的神经记录设备，并用辅助工具来增强这些技术，以使大脑的动态图像和解剖图像能够桥接。随着我们验证这些技术，我们将检查自闭症和精神分裂症小鼠模型的全脑神经动力学和解剖表型，执行全脑活动图，以表征与精神疾病相关的改变的计算。这样的地图可能从根本上开辟新的领域，思考精神疾病中分布的大脑回路是如何改变的，为新的治疗策略铺平道路。

DESCRIPTION (provided by applicant): One of the great challenges in neuroscience is to understand how the neurons of the brain work together as a circuit to compute behaviors, and how such circuit functions are changed in brain disorder states. There is a great need for technologies that enable the neural activity of large numbers of individual cells to be measured in the brain of a mammal such as a mouse - ideally throughout the entire brain, since we do not precisely know the exact set of cells involved with any behavior or brain disorder. We here propose two radical departures from the past, using computational and theoretical analyses to design new neural recording devices, and augmenting these technologies with supplementary tools to enable the bridging of dynamic and anatomical pictures of the brain. As we validate these technologies, we will examine whole-brain neural dynamics and anatomical phenotypes in autism and schizophrenia mouse models, performing whole-brain activity mapping to characterize the altered computations associated with psychiatric illness. Such maps may fundamentally open up new frontiers in thinking about how distributed brain circuits are changed in mental illness, paving the way to new treatment strategies.