Modulating Persistent Activity in Cortical Microcircuits

描述(由申请人提供)：这份K01(MRSDA)申请概述了在实验和理论方法方面的培训和监督研究，以了解调制对大脑网络行为的影响。这一建议的核心涉及对一个中心假设的调查，该假设认为大脑皮质网络的内在系综动力学将随着调节神经递质对系统的扰动而改变。该提案包括具体目标，以了解将在奖项范围内实现的孤立皮质网络的动态，以及制定一个实验和理论框架，以此作为延长职业目标的基础。 理论和实验在整个拟议的工作中被整合在一起，然而，奖项的初始阶段专注于学习和应用成像和电生理学技术来绘制大脑皮层切片中的网络行为图，并了解调制神经递质的影响。拟议工作的第二阶段更多的是理论上的，也包括KO1指南中所建议的说教阶段。最后阶段更多地面向职业发展，转化为完全独立的资金和研究，如NIMH KO1指导方针所述。候选人的长期目标是探索其他弥漫性影响对皮质功能的影响，如新陈代谢、压力和疾病，并将类似的研究推向体内准备。 候选人非常适合利用拟议的培训来调查短期和长期目标中概述的问题。候选人既有不同的实验背景，最近专注于神经退行性变的细胞生物学，也有在隔室水平和大规模时空模拟水平上建立详细生物物理模型的理论经验。提案中概述的先进成像技术、在哺乳动物系统水平上的工作以及理论技术对候选人来说都是新的。实验和理论导师都是各自领域的领导者，是拟议中的培训的理想人选。纽约大学和库兰特研究所为理论和实验互动提供了丰富的环境，实验导师为哥伦比亚大学拟议的实验工作提供了装备精良的实验室。最后，候选人按照KO1准则的建议，提议成立一个咨询委员会，就拟议工作的各个方面进行磋商。

DESCRIPTION (provided by applicant): This K0l (MRSDA) application outlines training and supervised research in both experimental and theoretical approaches for understanding modulatory influences on cortical network behavior. The core of this proposal involves investigation of a central hypothesis that intrinsic ensemble dynamics of cortical networks will change in response to perturbations of the system by modulatory neurotransmitters. The proposal consists of specific aims for understanding the dynamics of isolated cortical networks to be accomplished within the award as well as the development of an experimental and theoretical framework on which to base extended career goals. Theory and experiment are integrated throughout the proposed work, however the initial phase of the award is focused on learning and applying imaging and electro-physiology techniques to map network behavior in cortical slices and understand the influence of modulatory neurotransmitters. The second period of the proposed work is more heavily theoretical, and also involves a didactic period as suggested in KO1 guideline. The final phase is more oriented towards career development, with translation towards fully independent funding and research as described in the NIMH KO1 guidelines. The candidate's long-term goals are to explore the effects of other diffuse influences on cortical function such as metabolism, stress and disease, and to move studies like these towards in-vivo preparations. The candidate is well suited to leverage the proposed training towards the investigation of the problems outlined in short and long-term goals. The candidate has both a diverse experimental background, most recently focused on the cell biology of neurodegeneration, and theoretical experience with detailed biophysical models at the compartment level as well as at the level of large-scale spatiotemporal simulations. The advanced imaging techniques, the work in mammals at a systems level and the theoretical techniques outlined in the proposal are new to the candidate. Both experimental and theoretical mentors are leaders in their respective fields and are ideal for the proposed training. NYU and the Courant Institute offer a rich environment for theory and experimental interactions, and the experimental mentor offers a superbly equipped laboratory for the proposed experimental work at Columbia. Finally, the candidate proposes an advisory committee, as suggested in KO1 guidelines, for consultation on various aspects of the proposed work.