Pontine control of respiratory rhythm and pattern: contribution of the Kölliker-Fuse nucleus

• Grant number: 25/03660-9
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: August 01, 2025
• End date: July 31, 2028
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Daniel Breseghello Zoccal
• Grantee: Isabela de Paula Leirão
• Host Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated research grant: 22/05717-0 - Analyzing breathing irregularities during the post-natal period in spontaneously hypertensive rats, AP.R

Abstract

The rhythm and pattern of breathing are generated by the respiratory central pattern generator (rCPG), which consists of several well-described neural structures located on the ventral surface of the medulla. The activity of the rCPG is modulated by pontine inputs, particularly from the Kölliker-Fuse nucleus (KFn), through dense excitatory projections. Disruptions in KFn activity lead to significant effects on respiratory rhythm and pattern, highlighting the importance of this region in respiratory control. However, the connectivity of the KFn with other respiratory nuclei and its contribution to respiratory regulation remain speculative, posing a significant challenge to understanding the mechanisms of respiratory generation and modulation. Based on experimental evidence and computational studies, this project aims to investigate, through chemogenetic approaches (DREADD expression) and electrophysiological techniques in transgenic animal models, the influence of inhibitory projections from the nucleus of the solitary tract (NTS) and the Bötzinger complex (BötC) on KFn activity, as well as the impact of activating excitatory projections from the KFn to the BötC/pre-BötC on respiratory regularity and pattern. The results obtained will be crucial for a better understanding of the mechanisms regulating respiratory rhythm, regularity, and pattern, providing insights for developing therapeutic strategies for neurologically induced respiratory disorders. (AU)