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

Award Number: F31MH143524
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 12/18/2026
PERIOD OF PERFORMANCE END DATE: 12/17/2027

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


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $38,264 )
2026	2026	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	7000 FANNIN ST FL 9	HOUSTON	TX	77030	HARRIS	USA	Mental Health Research Grants	001	1	7/21/2026	NEW	$0
2026	2026	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	7000 FANNIN ST FL 9	HOUSTON	TX	77030	HARRIS	USA	Mental Health Research Grants	000	1	6/23/2026	NEW	$38,264
														Subtotal = $38,264

Grand Total All Awards = $38,264

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

Award Number: F31MH143524

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 12/18/2026

PERIOD OF PERFORMANCE END DATE: 12/17/2027

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