CAREER: Frontal cortical ensemble regulation of response execution and inhibition

这个项目有两个主要目标。第一个目标是了解大脑是如何计划和执行行动的，以及它是如何在不适当的时候抑制行动的（例如，当你看着你的糖摄入量时，抵制吃饼干的冲动）。第二个目标是描述神经科学研究中很大程度上被忽视的大脑区域——额极皮层的功能。这个领域已经在人类和其他灵长类动物中进行了一定程度的研究，但在很大程度上仍然是神秘的，并且在啮齿类动物中很少受到关注，而在啮齿类动物中可以进行彻底的生物学研究。在啮齿动物中已知的情况表明，它可能在行动执行/抑制过程中发挥关键作用，从而将一个重要的研究问题与相关但未被探索的大脑结构结合起来。这些研究使用了尖端的新技术，提供了大脑网络如何调节动作控制的高度精确和定量的特征，他们使用了一个新的行为框架，允许行为与大脑功能密切相关。它们还包括与一般公众的直接互动和对不同研究人群的支持，以加强这项研究与更广泛的社区之间的联系。了解大脑回路如何调节行为与多个学科相关，包括心理学和神经科学，以及人工智能和计算。这种理解也可以为涉及以行为控制紊乱为特征的疾病的研究提供信息，如注意缺陷多动障碍、成瘾、饮食失调、糖尿病、癌症等。前额叶皮层被反复确认为调节行为决策的关键大脑结构。额极皮层位于前额叶皮层的吻侧端，迄今为止很少受到研究的关注，特别是在啮齿动物中。有趣的是，对大鼠的早期损伤和刺激研究表明，额极皮层在抑制行为反应中起作用。从那时起，只有少数研究遵循了这一研究思路。这个项目的研究描述了额极神经元群在决定执行或抑制行为中的作用，并将开始全面了解这一大脑区域在行为中的作用。本提案的另一个目标是研究神经元的集合，以了解在相似或不同的行为背景下是什么塑造了集合级的响应特性。一些潜在的定义因素包括神经元的解剖位置、成员神经元之间的相关活动、共同的神经元投射目标和其他因素。该项目使用新颖的行为任务，高密度电生理记录（目标1），新的光遗传学工具来操作（目标2），以及解剖学追踪（目标3）在一个未被表征的大脑系统中与动作控制相关的神经元集合。目标4中的活动旨在提高对科学的认识和参与，特别是在代表性不足的社区成员中，部分通过关注决策及其在各个领域的作用。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

This project has two main goals. The first goal is to understand how the brain plans and executes actions as well as how it inhibits actions when they are inappropriate (for example, resisting the urge to take a cookie when watching your sugar intake). The second goal is to characterize the function of a brain region that has been largely neglected in neuroscience research – the frontal polar cortex. This area has been studied in humans and other primates to some degree but is still largely mysterious and has received little attention in rodents, where thorough biological studies can be performed. What is known in the rodent hints that it may play a key role in the action execution/inhibition process, thus merging an important research question with a relevant, but unexplored brain structure. These studies use cutting-edge new techniques to provide a highly precise and quantitative characterization of how brain networks regulate action control, and they use a new behavioral framework that permits close association of behavior with brain function. They also incorporate direct interaction with the general public and support for diverse research populations to strengthen ties between this research to the broader community. Understanding how brain circuits regulate action is relevant for multiple disciplines, including psychology and neuroscience as well as artificial intelligence and computation. This understanding may also inform research involving diseases characterized by disrupted action control such as attention deficit hyperactivity disorder, addictions, eating disorders, diabetes, cancers, and more. The prefrontal cortex is repeatedly identified as a critical brain structure regulating action decisions. The frontal polar cortex, at the rostral end of the prefrontal cortex, has received little research attention to date, particularly in rodents. Intriguingly, early lesion and stimulation studies in rats demonstrated a role for frontal polar cortex in inhibiting behavioral responses. Since then, only a few studies have followed this line of research. The research of this project characterizes the role of frontal pole neuron ensembles in decisions to execute or inhibit behavior and will begin to develop a comprehensive understanding of the role of this brain area in behavior. An additional goal of this proposal is to study ensembles of neurons to understand what sculpts ensemble-level response properties in similar or different behavioral contexts. Some potential defining elements to be explored include anatomical location of neurons, correlated activity among member neurons, common neuronal projection targets, and other factors. The project uses novel behavioral tasks, high-density electrophysiological recording (Objective 1), new optogenetic tools for manipulating (Objective 2), and anatomically tracing (Objective 3) neuron ensembles related to action control in an under-characterized brain system. Activities in Objective 4 are designed to increase awareness of and participation in science, particularly among members of underrepresented communities, in part through a focus on decision-making and its role across fields.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.