Testing the role of the left and right medial prefrontal cortex in fear extinction and anxiety with optogenetic manipulations

• Grant number: 18/05808-0
• Support type: Scholarships abroad - Research Internship - Post-doctor
• Effective date (Start): July 01, 2018
• Effective date (End): June 30, 2019
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal researcher: Cleopatra da Silva Planeta
• Grantee: Lucas Canto de Souza
• Supervisor abroad: Christa Mcintyre Rodriguez
• Home Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Research place: University of Texas at Dallas (UT Dallas), United States
• Associated to the scholarship: 16/08665-0 - Evaluation of left and right medial prefrontal cortex glutamatergic and GABAergic neurotransmissions in ethanol-induced consumption by social defeat stress in mice, BP.PD

Abstract

Rats submitted to the single prolonged stress (SPS) procedure demonstrate impaired fear extinction and increased anxiety, similar to those behavioral and physiological symptoms observed in posttraumatic stress disorder (PTSD) patients. The prefrontal cortex (PFC) plays a role in the modulation of emotional memory consolidation through its interactions with other brain regions like the amygdala and the bed nucleus of stria terminalis (BNST). Converging evidence indicates that extinction of fear memory requires plasticity in the medial prefrontal cortex (mPFC) and amygdala pathway. Furthermore, functional lateralization of the mPFC in the control of emotional states is observed after stress. In this sense, the loss of tonic left mPFC (LmPFC) inhibitory control over right mPFC (RmPFC) is related to the loss of resilience, contributing to the development of maladaptive responses, like impaired fear extinction and enhanced anxiety. In the present study, we will test the hypothesis that the tonic inhibitory control exerted by the LmPFC over RmPFC is impaired after the SPS, thus, resulting in impaired fear extinction and enhanced anxiety, and changes in expression of the activity regulated cytoskeletal-associated protein (Arc), a marker of neuronal plasticity, in the amygdala and BNST. To this end, we will use an optogenetic approach to stimulate/inhibit left or right mPFC neurons in the consolidation of extinction in SPS rats, as well as to test the effects on enhanced anxiety and Arc expression in the amygdala and BNST.