CRF Neurons in a Paraventricular Thalamic Circuit Regulate Food-approach vs. Threat-Avoidance Conflict

XU ZHANG ; DOUGLAS ENGELKE; JOHN OMALLEY; FERNANDEZ LEON, JOSE A.; SA LI; GILBERT KIROUAC; MICHAEL BEIERLEIN; FABRICIO DO MONTE

Denver

Conferencia; Computational and Systems Neuroscience (Cosyne) 2021; 2021

Balancing food-seeking with threat-avoidance behaviors is crucial for animals to survive, but the neural circuits that regulate this motivational conflict remain largely unknown. To answer this question, we designed an ethologically relevant ?approach-food vs. avoid-predator threat? conflict test in which rats need to overcome their fear of predator odor to reach food. During the test, cat saliva was positioned in the food area where rats were trained to press a lever for sucrose in the presence of an audiovisual cue. Rats exhibited robust defensive behaviors and a clear suppression in food-seeking responses in the presence of the predator odor. Using in situ hybridization, immunohistochemistry and in vivo single-unit recordings from photoidentified cell-types, 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 during conflict. Chemogenetic inactivation of aPVTCRF neurons during conflict restored food-seeking behavior and reduced defensive responses, but had no effect when the predator odor or the food-seeking tasks were carried out independently. Using both anterograde and retrograde viral tracing methods, we characterized the anatomical connectivity between aPVTCRF neurons and brain regions that are implicated in the regulation of food seeking and defensive responses. aPVTCRF neurons project densely to the nucleus accumbens (NAc), and optogenetic activation of the aPVTCRF-NAc pathway recapitulated the predator-odor induced food-seeking suppression and avoidance responses by mediating target-dependent synaptic transmission in the NAc. In addition, we identified the ventromedial hypothalamus (VMH) as a critical input to aPVTCRF neurons, and demonstrated that aPVT-projecting VMH neurons are activated by predator odor and synapse onto NAc-projecting aPVT neurons. Chemogenetic inactivation of aPVT-projecting VMH neurons reduced defensive behaviors exclusively during conflict. Together, our findings describe a subpopulation of neurons in a hypothalamic-thalamostriatal circuit that suppresses reward-seeking behavior under the competing demands of avoiding threats.