The role of the glucocorticoid receptors on the dorsal hippocampus of Wistar rats at time-dependent fear generalization

• Grant number: 21/13785-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2022
• End date: May 31, 2023
• Field of knowledge: Humanities - Psychology - Physiological Psychology
• Principal Investigator: Raquel Vecchio Fornari
• Grantee: Ana Carolina Quintiliano dos Santos
• Host Institution: Centro de Matemática, Computação e Cognição (CMCC). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil

Abstract

Stressful situations, such as contextual fear conditioning training (CFC), elicit the release of glucocorticoids. These hormones bind to glucocorticoid receptors (GR) in the central nervous system and modulate the consolidation of the memory trace created during the training. Over time, the emotional memory will undergo systems consolidation, a process by which memory dependence is reorganized across several cortical regions, such as the dorsal hippocampus (dHPC). During this process, the memory trace may lose some of its specificity to contextual features in remote retrieval tests, a phenomenon known as a time-dependent fear generalization, that is possibly linked to the plasmatic levels of corticosterone after conditioning. This phenomenon is possibly associated with post-training plasma corticosterone (CORT) levels, with low CORT levels eliciting fear discrimination at remote time points and high levels, generalized fear. Despite the evidence that glucocorticoids are involved in modulating contextual specificity, the role played by the GRs in the dHPC in this process is still unknown. To answer this question, we will investigate how the blockage of hippocampal GRs modulates the time-dependent generalization of fear memories. For that, Wistar rats will undergo CFC training and after immediately that, mifepristone, a GR antagonist, will be administered into the dHPC. After an interval of 2 or 28 days, these animals will be exposed to a novel context and then to the training context so we can evaluate the specificity of fear memory. These results will contribute to the understanding of pathological fear generalization, which can be observed in several psychiatric conditions, such as post-traumatic stress disorder, depression, and phobias.(AU)