Infralimbic cortex circuits involved in disruption of fear conditioning processing caused by severe stress in male and female rats

• Grant number: 23/04565-4
• Support Opportunities: Scholarships abroad - Research
• Start date: August 01, 2023
• End date: July 31, 2024
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Carlos Cesar Crestani
• Grantee: Carlos Cesar Crestani
• Host Investigator: James Paul Herman
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Institution abroad: University of Cincinnati, United States

Abstract

Traumatic stress exposure elicits behavioral and physiological responses that can compromise health and well-being, generating brain changes that can intrude on appropriate emotional regulation. Numerous disease states, most notably post-traumatic stress disorder (PTSD), share behavioral and physiological dysfunctions typical of traumatic stress exposure, indicative of a link between stress and the disease. This proposal queries the neurocircuitry underlying lasting behavioral pathologies linked to severe stress, focusing on the role of intralimbic cortex (IL) connections. Prior research present strong evidence for reduced IL excitability and excitatory synaptic drive following severe stress exposure, and functional hypoactivity of the human IL homolog is associated with PTSD. This proposal is designed to understand the mechanisms underlying stress-induced IL hypofunction, concentrating on changes in afferent connectivity. The study is designed to test the necessity and sufficiency of IL afferent connections in causing long-lasting severe stress-induced dysfunctions in adaptation (extinction) and reinstatement of fear conditioning, using a rat model of trauma exposure [single prolonged stress (SPS)]. The role of IL inputs from the prelimbic cortex (PL) and the ventral hippocampus (vHPA) in SPS-induced dysfunction of fear conditioning processing will be tested using viral vector-mediated expression of excitatory and inhibitory DREADDs. Results of this study might support the development of new pharmacological and/or circuit-targeting intervention strategies to promote stress resilience in individuals exposed to traumatic or severe stress. (AU)