The cortico-amygdala control of active avoidance response face to a stressor

• Grant number: 24/14391-6
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: February 01, 2025
• End date: January 31, 2026
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Carolina Demarchi Munhoz
• Grantee: Vitor Augusto Laurino Juliano
• Supervisor: Leonardo Santana Novaes
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Max-Planck Institute For Biological Cybernetics, Germany
• Associated to the scholarship: 21/13524-4 - 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, BP.DD

Abstract

Stress constitutes a significant risk factor for psychiatric disorder development, such as post-traumatic stress disorder (PTSD). Some of PTSD's characteristic symptoms are impaired fear extinction and avoidance. The neurobiological mechanisms governing the fear extinction deficit and avoidance are extensively studied in rodent models through Pavlovian and instrumental conditioning. The medial prefrontal cortex (mPFC) - composed of infralimbic (IL) and prelimbic (PL) subdivisions - and the amygdala are stress-responsive structures involved in fear-related processes, engaged in both Pavlovian-based fear conditioning and active avoidance tasks. Previous results from our lab demonstrate that acute stress induces fear extinction deficit in animals submitted to Pavlovian-based contextual fear conditioning 10 days after stress exposure, along with a stress-induced decrease in IL and IL to basolateral amygdala complex (BLA) projections activity and an increase in BLA and BLA to IL projections activity. We verified that specific deletion of acute stress-responsive BLA neurons prevented decreased stress-induced IL activity and the delayed fear extinction deficit. Evidence presented in the literature also points out that the communication between mPFC and the amygdala - especially its central nucleus (CeA) - is crucial for active avoidance response, safety/fear cue discrimination, and stimulus valence and salience encoding. Here, we aim to describe how IL to CeA projections coordinate the animal's behavioral strategy adopted face to a stressor (footshocks) during the active avoidance task. This study will increase our understanding of how mPFC-amygdala circuitries are involved in stress-related behavioral responses.