Study of the role of orexinergic mechanisms in the dorsal hippocampus in contextual fear conditioning

• Grant number: 23/00888-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2023
• End date: December 31, 2023
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Rafael Carvalho Almada
• Grantee: Gabriela Marie Ferreira Suzuki
• Host Institution: Faculdade de Ciências e Letras (FCL-ASSIS). Universidade Estadual Paulista (UNESP). Campus de Assis. Assis , SP, Brazil
• Associated research grant: 18/03898-1 - Fear and anxiety: role of the orexinergic system in the medial prefrontal cortex, AP.JP

Abstract

The ability to detect and predict threatening or stressful events is essential for survival. The dorsal hippocampus (DH) has been the subject of studies in the field of neuroscience, especially given the evident participation of this brain structure in mnemonic processes and the control of emotions. The hypothalamus is also implicated in regulating these processes, and the hypothalamic neuropeptide orexin (hypocretin) appears to be involved in processing fear and anxiety states. Recent studies have correlated the orexinergic system with the neurobiology of emotions, such as in the modulation of learned fear. However, little is known about the role of orexinergic mechanisms in HD during the organization and expression of behavioral responses in conditioned fear. This study aims to investigate the role of orexinergic mechanisms in DH during the acquisition, consolidation, and expression of contextual fear conditioning. For this, the mice will receive injections of the selective antagonist of type 1 orexinergic receptor (OX1R), SB 334867 (300 nM) in the DH, before the conditioning session or before the test session of the contextual fear conditioned. The hypothesis is that the pharmacological blockade of OX1Rs promotes a decrease in freezing responses in both sessions, demonstrating the modulatory role of the orexinergic system on the organization and expression of learned fear.