Study of the involvement of nitrergic and glutamatergic systems in the extinction deficit of aversive memory of context-conditioned fear in stressed mice

• Grant number: 24/00561-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2024
• End date: December 31, 2024
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Leonardo Resstel Barbosa Moraes
• Grantee: Sarah Solovi Rodrigues
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The extinction process of aversive memory plays a crucial role in the emotional regulation of individuals. When this process fails to function properly, psychiatric disorders such as anxiety and post-traumatic stress disorder (PTSD) can arise. To gain a better understanding of the neurobiological mechanisms involved in aversive memory extinction, experimental fear conditioning models in rats and mice have been used. One of these models is the context fear conditioning (CFC), where the animal associates an aversive stimulus with a specific context. Studies have shown that previously stressed animals exhibit alterations in memory and aversion processes related to this model. The behavioral similarities observed between stressed animals and individuals with PTSD make the stress model a valuable tool for translational research. The interaction between NMDA glutamate receptors and nitric oxide (NO) in the extinction processes of CFC has been described as important. NMDA receptors are a subcategory of glutamate receptors and play a crucial role in synaptic plasticity and memory formation. NO has been identified as a crucial modulator of NMDA receptor functions. Recent studies have shown that stress can affect NMDA receptor activity and NO signaling, which may impact aversive memory extinction processes.Therefore, this project aims to evaluate whether NMDA receptors and NO are involved in the alterations observed in aversive memory extinction processes in male C57 mice stressed by the Stress and Re-stress (SRS) protocol and subjected to the CFC extinction model. Additionally, we will quantify neuron activation in brain regions involved in memory extinction, such as the prefrontal cortex and hippocampus, as well as the colocalization with enzyme that synthetase NO in these structures. These analyses will be conducted at different time points during the memory process. In view of the above, the project hypothesis is that there is an interaction between NMDA receptors and nitric oxide (NO) in the alterations observed in stressed animals subjected to the CFC extinction model.