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Glucocorticoid signaling leading to the neuronal hyperexcitability of the basolateral amygdala complex and its effects on anxiety and aversive memory extinction.

Grant number: 22/08766-1
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Start date: October 01, 2022
End date: December 31, 2023
Field of knowledge:Biological Sciences - Pharmacology - Neuropsychopharmacology
Principal Investigator:Carolina Demarchi Munhoz
Grantee:Taynara da Cruz Nascimento
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Stress is critical in developing neuropsychiatric disorders such as post-traumatic stress disorder (PTSD). This relationship is mediated by changes in brain structures, such as the basolateral amygdala complex (BLA), whose activity is increased in the face of stressful experiences and is associated with the manifestation of fear and anxiety, in addition to mediating the extinction of aversive memories, which is impaired in stress disorders. Several studies have already highlighted the importance of glucocorticoid hormone (GCs) signaling in the intercommunication of stress, amygdala, and the underlying behavioral manifestations. However, there is still a need to understand the relationship between stress, neuronal hyperexcitability in the BLA [and its intercommunication with other essential structures, mainly the hippocampus (HPC) and medial prefrontal cortex (mPFC)], with the development of stress-associated mood disorders such as anxiety and aversive memory extinction deficit. Thus, this project aims to modulate, using viral vectors, the neuronal excitability in the BLA (SK2-HSV) to verify whether the late anxiety and late fear memory extinction deficit triggered by acute stress depend on these events and whether they modify the intercommunication with the HPC and CPFm. We feel that the results obtained here will bring vital knowledge to advance our understanding of the neurobiological mechanisms involved in the stress response.

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