Role of Hippocampal-Hindbrain Circuitry in Stress Habituation in Male and Female Rats

• Grant number: 23/15852-4
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: March 01, 2024
• End date: January 31, 2025
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Cristiane Busnardo Santiago
• Grantee: Luana Omena Giatti
• Supervisor: James Paul Herman
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Institution abroad: University of Cincinnati, United States
• Associated to the scholarship: 23/00306-4 - Study of the effect of inactivating previously activated neurons in the hippocampus during repeated chronic stress in c-fos-lacZ transgenic rats on the habituation process of autonomic, neuroendocrine and neuroinflammatory responses, BP.DD

Abstract

Emotional stress disrupts the body's physiological and psychological equilibrium and is linked to several pathologies, including cardiovascular diseases and psychiatric disorders. Stressful stimuli increase cardiovascular activation, marked by increased mean arterial pressure (MAP) and heart rate (HR), along with HPA axis activation, resulting in elevated corticosterone and adrenocorticotrophin (ACTH) plasma levels. These changes are often accompanied by emotional consequences including anxiety- and depression-like behaviors. When exposed to prolonged or repeated real or potential threats, the body initiates adaptive processes in order to minimize the impact of stress. However, despite the significance of stress response habituation, our understanding of the neural pathways involved in this process remains unclear. The hippocampus is an important brain regulator of responses to chronic stress, due largely to indirect anatomical connections with the HPA axis. In addition, it has been demonstrated that chronic stress can cause functional and structural changes in the hippocampal region. In this sense, the glutamatergic system within the ventral hippocampus (vHip) plays a critical role in processes related to neuronal plasticity, synergistically working with glucocorticoids, and is associated with control of stress and emotions. Importantly, thereare documented sex differences in hippocampal plasticity, cognitive functions, and in several mental disorders target the integrity of hippocampus. This proposal tests the hypothesis that glutamatergic projections from the hippocampus is required for habituation of hormonal and behavioral stress responses following chronic stress. We will test the effect of chemogenetic silencing (using Designer Receptors Exclusively Activated by Designer Drugs - DREADDs) of glutamatergic neurons in vHip in to test its role in development of chronic stress habituation in key stress regulatory circuits, includingCRFergic neurons and catecolaminergic neurons in these brain structures that connect directly or indirectly with vHip in male and female rats.