Neuroplasticity in the basolateral complex of amygdala and on anxiety and extinction memory circuit mediated by glucocorticoids via GR

• Grant number: 18/15982-7
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Effective date (Start): March 01, 2020
• Effective date (End): July 31, 2023
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Carolina Demarchi Munhoz
• Grantee: Letícia Morais Bueno de Camargo
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Given the increase in the occurence of stressful factors on everyday life, mainly on large cities, the incidence of depression and anxiety disorders, such as generalized anxiety and Post Traumatic Stress Disorder (PTSD), also increases and has raised the attention of the World Health Organization (WHO). Therefore, the demand for studies concerning the neurobiological mechanisms involved on these disorders is also increasing. In murine models, one hour acute restraint stress or acute corticosterone (CORT) treatment promotes an anxiety-like behavior 10 days after, due dendritic remodeling in basolateral complex of amygdala (BLA). During my Scientific Initiation (FAPESP 2016/21559-4), we observed that this behavior development occurs preferably through the nongenomic actions of the glucocorticoids receptor on this structure. Data from our group, along with those from scientific literature, show that increased CORT levels enhance emotional memories consolidation, like fear conditioning and extinction but in a time-dependent manner, making the neuroplasticity caused by the increase on these hormones levels an important point of study. Anxiety and aversive memories consolidation and extinction are controlled by neural circuits that includes the BLA and its afferents and efferents projections with the medial prefrontal cortex (mPFC) and the hippocampus. Studies have shown a AMPA and NMDA's trafficking increase due GCs by GR after an acute stress session. Thus, to determine if the neuroplasticity on the BLA and these structures occurs by GCs actions mediated by GR, we propose blocking those projections to the BLA using viral constructs during the extinction protocol. Additionally we will analyze GCs/GR modulation on glutamatergic signalling on the BLA and its implication on acute stress-induced deficits in acquisition and extinction of aversive memories. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

NOVAES, LEONARDO SANTANA; BUENO-DE-CAMARGO, LETICIA MORAIS; MUNHOZ, CAROLINA DEMARCHI. Environmental enrichment prevents the late effect of acute stress-induced fear extinction deficit: the role of hippocampal AMPA-GluA1 phosphorylation. TRANSLATIONAL PSYCHIATRY, v. 11, n. 1, JAN 5 2021. (18/19599-3, 18/15982-7, 12/24002-0, 19/00908-9, 16/03572-3)