INSPIRE Track 2: Molecular Brain Connectomics: from Genes to Cognition

这一INSPIRE奖汇集了生物科学局综合组织系统司、工程局化学、生物工程、环境和运输系统司以及社会、行为和经济科学局行为和认知科学司传统上支持的研究领域。认知产生于复杂大脑回路中的活动。这些大脑回路是根据一个物种的基因蓝图进行布局的。过去和现在在揭示认知的生物学基础方面取得的成功包括：发现了人脑中支持特定认知功能的区域，确定了特定细胞类型在小鼠等动物的行为中所起的作用，以及日益详细地了解了特定基因及其变化对健康和疾病中认知功能的影响。这项在洛克菲勒大学进行的跨学科项目的目标是直接确定对高级认知功能至关重要的大脑回路元素的遗传特异性。这个项目将具有重大意义，1)阐明生物组织的复杂性，从基因水平，通过细胞类型，大脑区域，神经回路到行为，2)开发新技术，使研究人员能够以模型生物的精确度和特异性剖析潜在认知的大脑回路，以及3)提高对遗传变化如何影响认知的理解。这个将认知神经科学、神经系统和神经技术结合在一起的跨学科项目预计将对社会产生更广泛的影响，它将为人类思维的一些最深层次的问题提供见解，并提供独特的教育和推广机会，以提高公众对大脑组织和功能的理解。该项目将研究支持认知功能的多结点大脑回路的遗传特异性。该电路将通过功能和结构的脑部成像进行定位。然后，将使用尖端分子技术确定多个回路节点内投射神经元的遗传表达模式。然后，将通过先进的定制设计的光遗传学和电生理技术来确定连接节点的投射神经元的功能。然后，同样的光遗传学方法将被用于对认知和情绪行为中的投射神经元进行因果询问。结合基因表达和功能数据，就可以预测人类基因中的特定多态可能如何改变认知-情绪能力。这些预测将通过大脑功能成像和对基因分型受试者的行为测试来验证。总而言之，这些研究将提供对大脑回路和基因基础的深刻见解，这些基础使人类大脑的认知功能成为可能。

This INSPIRE award brings together research areas traditionally supported in the Division of Integrative Organismal Systems in the Directorate for Biological Sciences, in the Division of Chemical, Bioengineering,Environmental, and Transport Systems in the Directorate for Engineering, and in the Division of Behavior and Cognitive Sciences in the Directorate for Social, Behavioral and Economic Sciences. Cognition arises from the activity within complex brain circuits. These brain circuits are laid out according to a species' genetic blueprint. Past and current successes in uncovering the biological basis of cognition include the discovery of areas in the human brain supporting specific cognitive functions, the determination of the roles that specific cell types play in the behavior of animals like the mouse, and the increasingly detailed understanding of the impact specific genes and their alterations can have on cognitive functions in health and disease. The goal of this interdisciplinary project, conducted at The Rockefeller University, is to directly determine the genetic specificity of brain circuit elements that are critically important for high-level cognitive function. This project will be significant by 1) elucidating the complexity of biological organization from the level of genes, through cell types, brain areas, and neural circuits to behavior, 2) developing new technology that will allow researchers to dissect brain circuits underlying cognition with the precision and specificity of model organisms, and 3) improving the understanding of how genetic alterations impact cognition. The interdisciplinary project at the interface of cognitive neuroscience, neural systems, and neurotechnology, is expected to have broader impacts on society by providing insights into some of the deepest questions about the human mind and by offering unique educational and outreach opportunities to improve public understanding of the organization and function of the brain.The project will investigate the genetic specificity of a multi-node brain circuit that supports cognitive function. The circuit will be localized with functional and structural magnetic brain imaging. Genetic expression patterns of projection neurons within multiple circuit nodes will then be determined using cutting edge molecular techniques. The functions of the projection neurons linking the nodes will then be determined through advanced and custom-designed optogenetic and electrophysiological techniques. The same optogenetic approach will then be used for causal interrogation of projection neurons in cognitive and emotional behaviors. Combining the gene expression and functional data, predictions for how specific polymorphisms in human genes may alter cognitive-emotional abilities will be generated. These predictions will be tested through functional brain imaging and behavioral testing of genotyped subjects. Together, these investigations will provide deep insights into the brain circuits and genetic underpinnings that make possible the cognitive functions of the human mind.