Investigating the role of prefrontal cortex circuits in risky decision-making

The National Institute of Mental Health awarded the University of Texas Health Science Center at Houston $114,792 on December 18, 2026, under the Mental Health Research Grants program (CFDA 93.242) to investigate the role of prefrontal cortex circuits in risky decision-making. The project runs through December 22, 2027, with performance at Houston, Texas.

The research identifies neural mechanisms controlling the balance between reward seeking and threat avoidance by examining approach-avoidance conflict—the behavioral tension that emerges when contextual cues signal both rewards and threats simultaneously. Using a food-approach versus predator-avoidance conflict model in rats, the investigator has identified individual variability in food-seeking and defensive behaviors, with rats displaying either risk-taking responses (approaching food areas and pressing levers during food cues) or risk-avoiding responses (avoiding food areas and not pressing levers). The study focuses on the prelimbic subregion of the medial prefrontal cortex, a brain region critical for cued reward seeking and contextual fear memory. Preliminary in vivo electrophysiological recordings revealed differences between risk-taking and risk-avoiding responses during contextual conflict. Candidate regions for differential regulation of prefrontal activity during approach versus avoidance responses include the ventral tegmental area and ventral hippocampus. Understanding these neural circuits has implications for neuropsychiatric disorders characterized by imbalanced approach-avoidance behavior, including substance abuse, eating disorders, and anxiety disorders.

Abstract

Approach-avoidance conflict emerges when contextual cues signaling rewards or potential threats CO-occur in time and space. Resolving approach-avoidance conflict requires animals to integrate reward and threat information and assign motivational values to associated cues to make appropriate behavioral decisions. An imbalance in approach-avoidance behaviors is associated with neuropsychiatric disorders. For instance, excessive reward approach is a hallmark of substance abuse and eating disorders, whereas excessive avoidance is a symptom of anxiety disorders. However, the neural circuits that regulate reward and threat cues to drive behavioral choices during conflict remain unknown. Therefore, the long-term goal of the proposed study is to identify the neural mechanisms that control the balance between reward seeking and threat avoidance. Using a food-approach VS. Predator-avoidance conflict model, i have identified individual variability in food seeking and defensive behaviors during a contextual memory test. Rats displayed either: i) risk-taking responses, in which they approach the food area and press the lever during food CUE presentation, or II) risk-avoiding responses, in which they avoid the food area and do not press the lever during food cues. To explore the neural mechanisms that mediate these two behavioral responses, i focus on the prelimbic subregion (PL) of the medial prefrontal cortex (mpfc), a brain region critical for cued reward seeking and contextual fear memory. My preliminary in vivo electrophysiological recordings from PL neurons in response to food cues revealed differences between risk-taking and risk-avoiding responses in the same rats during contextual conflict. Candidate regions that may differentially regulate PL activity during approach VS. Avoidance responses are the ventral tegmental area (VTA) and the ventral hippocampus (vhip). Prior studies suggest that dopaminergic VTA (vtada) inputs to the mpfc enhance reward-CUE encoding to drive motivated behaviors, whereas glutamatergic vhip (vhipglut) inputs to PL regulates contextual fear expression. Thus, the objective of this study is to investigate the functional roles of VTA and vhip projections to PL during conflict and how these inputs shape risky decision-making. My central hypothesis is that differences between risk-taking and risk-avoiding behaviors are mediated by how context and food CUE information are conveyed to PL. To test this, in aim 1, i will use fluorescent biosensors and fiber photometry to evaluate whether differences between risk-taking and risk-avoiding within the same rats are associated with distinct levels of dopamine and glutamate release in PL and different patterns of activity in vtada and vhipglut inputs in PL. In aim 2, i will optogenetically silence vtada and vhipglut neurons and image dopamine and glutamate dynamics in PL during food CUE trials to investigate if these inputs regulate risk-taking and risk-avoiding behaviors. This proposal will use an ethologically-relevant model that resembles approach-avoidance conflict in nature to explore how understudied mesocortical and hippocampal-cortical pathways encode information of opposite valence to regulate motivated behaviors during conflict.