The role of glucocorticoid and norepinephrine in the basolateral amygdala complex-medial prefrontal cortex-locus coeruleus microcircuitry on the delayed acute social defeat stress-induced fear extinction deficit in mice

• Grant number: 21/13524-4
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Effective date (Start): June 01, 2022
• Effective date (End): August 31, 2027
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Carolina Demarchi Munhoz
• Grantee: Vitor Augusto Laurino Juliano
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 24/14391-6 - The cortico-amygdala control of active avoidance response face to a stressor, BE.EP.DD

Abstract

Stress is a crucial risk factor for the emergence of psychiatric disorders, such as Post-traumatic Stress Disorder (PTSD). The BLA and the medial prefrontal cortex (mPFC; infralimbic and prelimbic subdivisions, IL-mPFC and PL-mPFC, respectively) are related to the expression of fear and fear extinction process. Locus Coeruleus (LC)’BLA neuronal projections (characterized by the abundant release of norepinephrine [NE]) are involved with the stress-induced fear extinction deficit. Data from our group demonstrate that acute restraint stress promotes the delayed fear extinction deficit associated with increased activity of BLA and PL-mPFC and the BLA’IL-mPFC projections, while the reduced activity of the IL-mPFC neurons. We verified that inhibition of NE-mediated signaling in BLA during fear conditioning reversed the stress-induced delayed fear extinction deficit. This project investigates how acute social defeat stress acts over BLA, CPFm and LC, including the connectivity between these structures, leading to delayed fear extinction deficit in mice and verify the possible influence of NE and glucocorticoid over BLA neurons for the development of this behavioral phenotype. This research will advance the understanding of the neurobiological mechanisms of stress-related psychiatric disorders. (AU)