Transcriptomic insights into the Locus coeruleus: BK channels, CO2 sensitivity, and their implications in panic disorder and respiration.

• Grant number: 24/22051-0
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: May 01, 2025
• End date: April 30, 2026
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Luciane Helena Gargaglioni Batalhão
• Grantee: Luis Gustavo Alexandre Patrone
• Supervisor: Russell Scott Ray
• Host Institution: Faculdade de Ciências Agrárias e Veterinárias (FCAV). Universidade Estadual Paulista (UNESP). Campus de Jaboticabal. Jaboticabal , SP, Brazil
• Institution abroad: Baylor College of Medicine, United States
• Associated to the scholarship: 21/13618-9 - Participation of calcium-activated potassium channels in respiratory, autonomic and behavioral responses to CO2/pH and in the chemosensitivity of LC neurons, BP.PD

Abstract

The locus coeruleus (LC) is a noradrenergic nucleus that exhibits sexual dimorphism and projects extensively throughout the brain, serving as the main source of central noradrenaline. Our research team was among the first to highlight the significance of the LC in mediating ventilatory and behavioral responses to CO2/pH in both male and female rodents. The chemosensitivity of these neurons varies with age, being higher in young neonatal rats (P10). This reduction correlates with an age-dependent increase in the expression of calcium-activated potassium (BK) channels in LC neurons during postnatal development, which coincides with a reduction in the neuronal chemosensitive response to CO2. Recent data obtained from our thematic project indicate that BK channels modulate the ventilatory response under hypercapnic conditions in a sex- and age-dependent manner. It is widely recognized that disruptions in the modulation of noradrenergic neurotransmission within the LC contribute to the development of several psychiatric conditions, such as panic disorder, where affected individuals show heightened sensitivity to CO2/pH. Additionally, the brain is known to detect acidity for various reasons beyond just ventilatory control, and a strong correlation exists between hypercapnia and panic disorder. Thus, this project aims to provide a better understanding of the role of BK channels in LC neurons throughout postnatal development, which may influence chemosensitive responses to CO¿/pH and be associated with disorders characterized by abnormal central CO2 sensing. We will also evaluate transcriptionally the profile of LC after CO2-induced panic attack.