Neurobiology of Motivational Modulation of Sustained Attention by Signaled Reward

描述(由申请者提供)：这个培训和研究奖项将为候选人作为一名分子和行为神经学家的独立职业生涯做好准备，使用严格的行为和基因操作来分析动机和认知之间相互作用的大脑回路。应聘者是一名实验心理学家，在动物学习和行为领域拥有丰富的专业知识。根据该奖项提供的培训将在哥伦比亚大学精神病学和神经科学系进行，使应聘者能够1)发展分子神经科学方面的实验室技能；2)扩大他在分子遗传学和翻译神经科学方面的知识，使他能够独立开发新的科学想法，将他的研究成果与现有知识结合起来，并将其与临床实践联系起来；3)在专业发展方面接受指导；以及4)对科学实践中固有的伦理问题产生深刻的理解。培训目标将通过实践培训、正式指导、与经验丰富的独立调查人员的咨询、课程作业、研讨会出席和专业科学会议相结合的计划来实现。该奖项支持的研究将阐明动机和认知之间相互作用的功能神经回路。动机和认知缺陷存在于许多精神疾病中，大量文献记录了动机变量对认知表现的影响，但这些影响的神经基础还没有被很好地理解。这位候选人为小鼠开发了一种新的行为范式，其中评估持续注意力的辨别程序的表现可以在逐个试验的基础上通过明确发出正确选择的奖励概率的信号来调节。使用此范例作为 作为方法论基础，这项拟议的研究将使用一种遗传技术来沉默基底前脑、前额叶和纹状体中的特定神经群，以确定通过发出信号的奖励概率对持续注意表现进行动机调节所必需和充分的功能神经回路。这项研究将阐明动机调节认知的功能神经回路，这将加深我们对动机和认知生物学的理解，并可能深入了解临床人群中功能障碍的神经基础。 与公共卫生相关：动机和认知方面的衰弱损害存在于许多精神疾病中，并且动机与认知在产生功能障碍方面存在相互作用。本研究将阐明参与持续注意的动机调节的功能神经回路，并可能对参与患者功能损害的神经回路提供洞察。

DESCRIPTION (provided by applicant): This training and research award will prepare the candidate for an independent career as a molecular and behavioral neuroscientist using rigorous behavioral and genetic manipulations to analyze the brain circuits underlying the interaction between motivation and cognition. The candidate is an experimental psychologist with significant expertise in the area of animal learning and behavior. Training provided under this award will take place at Columbia University's Departments of Psychiatry and Neuroscience and will enable the candidate to 1) develop laboratory skills in molecular neuroscience; 2) expand his knowledge of molecular genetics and translational neuroscience so that he can independently develop novel scientific ideas, integrate his research findings with current knowledge, and relate them to clinical practice; 3) receive mentorship in professional development; and 4) develop a strong understanding of the ethical issues inherent in the practice of science. The training goals will be accomplished through a program combining practical training, formal mentorship, consultations with experienced independent investigators, coursework, seminar attendance, and professional scientific meetings. The research supported under this award will elucidate the functional neurocircuitry underlying the interaction between motivation and cognition. Deficits in motivation and cognition are present in a number of psychiatric diseases, and a large literature has documented effects of motivational variables on cognitive performance, but the neural basis of these effects is not well understood. The candidate has developed a novel behavioral paradigm for mice in which performance of a discrimination procedure which assesses sustained attention can be modulated on a trial by trial basis by explicitly signaling the probability of reward for correct choices. Using this paradigm as a methodological foundation, the proposed research will use a genetic technique to silence specific neural populations in the basal forebrain, PFC, and striatum to determine the functional neural circuitry which is necessary and sufficient for motivational modulation of sustained attention performance by signaled reward probability. The proposed research will elucidate the functional neural circuitry by which motivation modulates cognition, which will further our understanding of the biology of motivation and cognition, and may give insight into the neural underpinnings of the functional impairments in clinical populations. PUBLIC HEALTH RELEVANCE: Debilitating impairments in motivation and cognition are present in a number of psychiatric diseases, and motivation has been suggested to interact with cognition in producing functional impairment. The present research will elucidate the functional neural circuitry involved in motivational modulation of sustained attention and may provide insight into the neural circuitry involved in functional impairments in patients.