CAREER: Frontal cortical ensemble regulation of response execution and inhibition

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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.