[F31] Investigating the role of prefrontal cortex circuits in risky decision-making
Ente: National Institute of Mental Health
Scadenza: 2027-12-22
Importo max: 38.264 EUR
Paese: US
Descrizione
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. T
Istituzione: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
PI: Vicky Chuong
Progetto: 1F31MH143524-01
Settori: National Institute of Mental Health
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