Flexibly adjusting food-seeking behaviors based on metabolic needs and environmental threats is crucial for animal survival. In humans, maladaptive food-seeking behaviors that contravene energy homeostasis, which is often driven by food-associated cues with hedonic reward values, lead to obesity and eating disorders. However, the neural mechanisms underlying the modulation of cued food-seeking behaviors by distinct metabolic and threat states remain elusive. Using an approach-food vs. avoid-predator threat conflict test in rats, we identified a subpopulation of neurons in the anterior portion of the paraventricular thalamic nucleus (aPVT) which express corticotrophin-releasing factor (CRF) and are preferentially recruited to respond to food cues during threat state. Then, we used anatomical tracing, chemogenetic and optogenetic manipulation to identify a neural circuit from the VMH via aPVTCRF neurons to the NAc shell that suppresses food-seeking behaviors in the presence of predator-related odor. Next, by using in vivo single-unit recordings from projection-defined neurons in the prelimbic cortex (PL), an input source of aPVTCRF neurons, and chemogenetic manipulations of distinct PL circuits, we found that divergent PL projections to the PVT or the NAc mediate either hedonic feeding during satiation or feeding suppression during threat, respectively. Furthermore, we elucidated the populational and neuronal coding of metabolic or threat states in PL through their food cue responses and spontaneous activities. Together, our findings revealed a unified mechanism whereby internal metabolic or emotional states regulate learned food-seeking behaviors by recruiting distinct neuronal populations to respond to environmental cues that predict food availability.
","abstract_html":"<p>Flexibly adjusting food-seeking behaviors based on metabolic needs and environmental threats is crucial for animal survival. In humans, maladaptive food-seeking behaviors that contravene energy homeostasis, which is often driven by food-associated cues with hedonic reward values, lead to obesity and eating disorders. However, the neural mechanisms underlying the modulation of cued food-seeking behaviors by distinct metabolic and threat states remain elusive. Using an approach-food vs. avoid-predator threat conflict test in rats, we identified a subpopulation of neurons in the anterior portion of the paraventricular thalamic nucleus (aPVT) which express corticotrophin-releasing factor (CRF) and are preferentially recruited to respond to food cues during threat state. Then, we used anatomical tracing, chemogenetic and optogenetic manipulation to identify a neural circuit from the VMH via aPVT<sup>CRF</sup> neurons to the NAc shell that suppresses food-seeking behaviors in the presence of predator-related odor. Next, by using in vivo single-unit recordings from projection-defined neurons in the prelimbic cortex (PL), an input source of aPVT<sup>CRF</sup> neurons, and chemogenetic manipulations of distinct PL circuits, we found that divergent PL projections to the PVT or the NAc mediate either hedonic feeding during satiation or feeding suppression during threat, respectively. Furthermore, we elucidated the populational and neuronal coding of metabolic or threat states in PL through their food cue responses and spontaneous activities. Together, our findings revealed a unified mechanism whereby internal metabolic or emotional states regulate learned food-seeking behaviors by recruiting distinct neuronal populations to respond to environmental cues that predict food availability.</p>","abstract_has_math":false,"creators":["Zhang, Xu","0000-0001-6062-0381
"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation (PhD)","degree_discipline":null,"degree_department":null,"school":null,"contributors":["Fabricio Do Monte","Michael Beierlein","Qingchun Tong"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2024,"date_issued":"2024-05-01T07:00:00Z","date_published":"2024-05-01T07:00:00Z","updated_at":"2026-07-24T05:48:59Z","subjects":["Prelimbic prefrontal cortex","paraventricular thalamus","satiation","predator threat","defensive behavior","internal states","food seeking","Behavioral Neurobiology","Computational Neuroscience","Systems Neuroscience"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1342","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Fabricio Do Monte","Michael Beierlein","Qingchun Tong"]},{"key":"dc:creator","label":"Author","values":["Zhang, Xu","0000-0001-6062-0381
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"]},{"key":"dc:title","label":"Title","values":["Mapping the neural circuits that underlie metabolic vs. emotional regulation of food-seeking behavior"]}]}],"canonical_facts":{"dc:contributor":["Fabricio Do Monte","Michael Beierlein","Qingchun Tong"],"dc:creator":["Zhang, Xu","0000-0001-6062-0381
"],"dc:date.available":["2025-04-16T07:00:00Z"],"dc:description.abstract":["Flexibly adjusting food-seeking behaviors based on metabolic needs and environmental threats is crucial for animal survival. In humans, maladaptive food-seeking behaviors that contravene energy homeostasis, which is often driven by food-associated cues with hedonic reward values, lead to obesity and eating disorders. However, the neural mechanisms underlying the modulation of cued food-seeking behaviors by distinct metabolic and threat states remain elusive. Using an approach-food vs. avoid-predator threat conflict test in rats, we identified a subpopulation of neurons in the anterior portion of the paraventricular thalamic nucleus (aPVT) which express corticotrophin-releasing factor (CRF) and are preferentially recruited to respond to food cues during threat state. Then, we used anatomical tracing, chemogenetic and optogenetic manipulation to identify a neural circuit from the VMH via aPVTCRF neurons to the NAc shell that suppresses food-seeking behaviors in the presence of predator-related odor. Next, by using in vivo single-unit recordings from projection-defined neurons in the prelimbic cortex (PL), an input source of aPVTCRF neurons, and chemogenetic manipulations of distinct PL circuits, we found that divergent PL projections to the PVT or the NAc mediate either hedonic feeding during satiation or feeding suppression during threat, respectively. Furthermore, we elucidated the populational and neuronal coding of metabolic or threat states in PL through their food cue responses and spontaneous activities. Together, our findings revealed a unified mechanism whereby internal metabolic or emotional states regulate learned food-seeking behaviors by recruiting distinct neuronal populations to respond to environmental cues that predict food availability.
"],"dc:identifier":["https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1342"],"dc:subject":["Prelimbic prefrontal cortex","paraventricular thalamus","satiation","predator threat","defensive behavior","internal states","food seeking","Behavioral Neurobiology","Computational Neuroscience","Systems Neuroscience"],"dc:title":["Mapping the neural circuits that underlie metabolic vs. emotional regulation of food-seeking behavior"],"thesis:degree_level":["Dissertation (PhD)"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T05:48:59Z"}