Neurobiology of Motivational Modulation of Sustained Attention by Signaled Reward

描述（由申请人提供）：该培训和研究奖将为候选人作为分子和行为神经科学家的独立职业做好准备，使用严格的行为和遗传操作来分析动机和认知之间相互作用的大脑回路。候选人是一位实验心理学家，在动物学习和行为领域具有重要的专业知识。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，并将使候选人能够1）发展分子神经科学的实验室技能; 2）扩展他的分子遗传学和转化神经科学知识，以便他能够独立开发新的科学思想，将他的研究成果与现有知识相结合，并将其与临床实践相结合; 3）接受专业发展的指导; 4）发展对科学实践中固有的伦理问题的深刻理解。培训目标将通过一个结合实践培训，正式指导，与经验丰富的独立调查人员，课程，研讨会出席和专业科学会议的咨询计划来实现。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性神经回路。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尚不清楚。候选人已经为小鼠开发了一种新的行为范例，其中评估持续注意力的辨别程序的性能可以通过明确地发出正确选择的奖励概率来在逐个试验的基础上进行调节。使用这种模式作为 作为方法学基础，这项研究将使用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，以确定功能性神经回路，这是通过信号奖励概率对持续注意力表现进行动机调制所必需和充分的。拟议的研究将阐明动机调节认知的功能神经回路，这将进一步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。 公共卫生相关性：动机和认知方面的削弱性损害存在于许多精神疾病中，并且动机已被认为与认知相互作用而产生功能损害。本研究将阐明持续注意的动机调制所涉及的功能性神经回路，并可能提供深入了解患者的功能障碍所涉及的神经回路。

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.