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

INSPIRE 轨道 2：分子脑连接组学：从基因到认知

• 批准号: 1343174
• 负责人: Winrich Freiwald
• 金额: $ 300万
• 依托单位: Rockefeller University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2020-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1343174&HistoricalAwards=false
• 关键词: INSPIRE; Track; Molecular; Brain; Connectomics

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.

该INSPIRE奖汇集了传统上支持生物科学局综合有机系统司，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的研究领域。认知产生于复杂的大脑回路中的活动。 这些大脑回路是根据物种的遗传蓝图来布置的。 过去和当前在揭示认知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发挥的作用，以及对影响的日益详细的了解特定基因及其改变可能对健康和疾病中的认知功能产生影响。 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大脑回路元件的遗传特异性。 该项目将具有重要意义：1）从基因水平阐明生物组织的复杂性，通过细胞类型，大脑区域和神经回路到行为，2）开发新技术，使研究人员能够以模型生物的精确性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的跨学科项目，通过提供对人类思维最深刻的问题的见解，并通过提供独特的教育和推广机会，提高公众对大脑组织和功能的理解，预计将对社会产生更广泛的影响。该项目将研究多基因遗传特异性，支持认知功能的节点脑回路。 电路将通过功能和结构磁脑成像进行定位。 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。 连接节点的投射神经元的功能将通过先进的和定制设计的光遗传学和电生理学技术来确定。 然后，相同的光遗传学方法将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，预测人类基因中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测试。 总之，这些研究将提供对大脑回路和遗传基础的深刻见解，这些回路和遗传基础使人类思维的认知功能成为可能。