Modulating Persistent Activity in Cortical Microcircuits

描述（由申请人提供）：此K01（MRSDA）应用程序概述了在实验和理论方法方面的培训和监督研究，以了解对皮层网络行为的调制影响。这个建议的核心涉及调查的一个中心假设，即皮质网络的内在合奏动力学将改变系统的调制神经递质的扰动。该提案包括理解孤立的皮层网络的动力学的具体目标，以在奖励以及实验和理论框架的基础上扩展的职业目标的发展。 理论和实验在整个拟议的工作中是一体化的，然而，该奖项的初始阶段侧重于学习和应用成像和电生理技术来映射皮层切片中的网络行为，并了解调节性神经递质的影响。建议工作的第二阶段更侧重于理论，也涉及KO1指南中建议的教学阶段。最后一个阶段更倾向于职业发展，如NIMH KO1指南所述，转化为完全独立的资金和研究。候选人的长期目标是探索其他扩散影响对皮质功能的影响，如新陈代谢，压力和疾病，并将这些研究推向体内制备。 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，又有详细的生物物理模型的理论经验，在隔间水平以及大规模时空模拟的水平。提案中概述的先进成像技术、系统层面的哺乳动物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，是拟议培训的理想选择。纽约大学和柯朗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的拟议实验工作提供了一个装备精良的实验室。最后，候选人提议按照KO1准则的建议设立一个咨询委员会，就拟议工作的各个方面进行协商。

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.