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

该INSPIRE奖汇集了传统上由生物科学理事会的综合有机体系统部门、工程理事会的化学、生物工程、环境和运输系统部门以及社会、行为和经济科学理事会的行为和认知科学部门支持的研究领域。认知产生于复杂大脑回路的活动。这些大脑回路是根据一个物种的基因蓝图来布局的。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人类大脑中支持特定认知功能的区域，确定特定细胞类型在小鼠等动物行为中所起的作用，以及对特定基因及其改变对健康和疾病中的认知功能的影响的日益详细的了解。这个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脑回路元素的遗传特异性。该项目将具有重要意义：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式生物的精度和特异性解剖认知基础的大脑回路；3)提高对遗传改变如何影响认知的理解。认知神经科学、神经系统和神经技术交叉的跨学科项目有望对社会产生更广泛的影响，为人类心灵的一些最深刻的问题提供见解，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节点脑回路的遗传特异性。该电路将通过功能和结构脑磁成像进行定位。投射神经元在多个电路节点内的遗传表达模式将使用尖端分子技术确定。连接节点的投射神经元的功能将通过先进和定制的光遗传学和电生理学技术来确定。同样的光遗传学方法将被用于认知和情感行为中投射神经元的因果询问。结合基因表达和功能数据，预测人类基因的特定多态性如何改变认知-情感能力。这些预测将通过功能性脑成像和基因型受试者的行为测试进行验证。总之，这些研究将提供对大脑回路和基因基础的深刻见解，使人类思维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.