CAREER: Defining the mechanistic role of striosomal microcircuits in decision-making

University Of Texas At El Paso, El Paso TX

Investigators

Abstract

Of the many decisions animals make daily, many entail choices that involve cost and reward. Since the dawn of neuroscience, researchers have sought to answer the question of how connected brain regions combine to produce decisions to complex problems. Previous work by the researchers of this project showed that the striosomal patches of the striatum are essential for integration of cost and benefit. In this project, the researchers test a multifaceted model of brain regions involved in complex decisions using advanced computational and experimental techniques. The model seeks to define the computational principles behind complex decisions involving cost and reward. To test this model, the researchers record and manipulate striosomal neuronal circuits in rats carrying out a novel, naturalistic cost-benefit decision-making task. The researchers apply novel machine learning concepts to aid identifying a mechanistic basis for the shift in circuit activity and decision-making between different decision-making contexts. In addition to pursuing the scientific objectives, the researchers develop and establish undergraduate and graduate courses that focus on the mechanisms of decision-making, and the analytical and experimental tools to study decision-making and neural circuit recordings. These courses aim to train future researchers to serve as critical thinkers that bridge experimental neuroscience and computation. Every day, humans and other animals make hundreds of decisions regarding food preference, cost avoidance, reproduction, and social interaction. The investigators’ recent research has provided the first clues that the striosomal compartments of the striatum are crucial gateways that affect the balance between the pursuit of reward and avoidance of costs during decision-making. Notably, striosomes selectively project to the lateral habenula (LH, predominant source of cost) and the dopaminergic neurons (DA) of the substantia nigra compacta (SNC, predominant source of reward). This Striosomal-DA-LH circuit is conserved across humans, monkeys, cats, rats, and even lampreys, and, therefore, understanding the role of this circuit in decision-making has broad implications. The investigators test the hypothesis that striosomes are a hub that affects interaction between the crucial players of the brain’s cost/reward evaluation system and, thus, influences subjective valuation of costs and rewards. To test this hypothesis, the investigators record and manipulate specific striosomal circuits in rats engaged in a novel, high-throughput decision-making task. Specifically, the investigators use high-throughput electrophysiology and Ca++ imaging to dissect the role of striosomal LH- and DA-projecting populations and an optogenetic approach to determine the causal role of each pathway in decision-making. Furthermore, using advanced computational modeling techniques, the investigators identify the computational principles that define how these circuits collectively mediate context-dependent decision-making states and influence choice behavior. The work is expected to reveal the role of striosomes in context-dependent perceptions of cost and benefit and their integration into one subjective value that affects decision-making. 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.