Control of abdominal expiratory activity by the preBötzinger complex

• Grant number: 22/12416-6
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Effective date (Start): May 01, 2023
• Effective date (End): April 30, 2024
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Daniel Breseghello Zoccal
• Grantee: Isabela de Paula Leirão
• Supervisor: Silvia Pagliardini
• Host Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Research place: University of Alberta, Canada
• Associated to the scholarship: 20/05045-6 - Control of breathing pattern: interactions between respiratory oscillators, BP.DR

Abstract

Rhythmogenic neurons of the pre-Bötzinger complex (preBötC), located in the ventral medulla, constitute the primary inspiratory oscillator that generates the respiratory rhythm. A second respiratory oscillator was described rostral to the preBötC in the lateral parafacial region (pFL), recruited during conditions of high respiratory drive to generate rhythmic expiratory contractions in the abdominal muscles (active expiration, AE). During the emergence of AE, it is speculated that interactions between the preBötC and pFL oscillators coordinate the inspiratory and expiratory motor activities. Although anatomical evidence indicates the presence of synaptic projections between these oscillators, the functional contribution of these connections remains controversial and elusive. In the current project, we will investigate the role of inhibitory projections from the preBötC to the pFL in controlling the expiratory pattern formation under baseline breathing and during exposure to low oxygen levels (hypoxia). We hypothesize that inhibitory inputs driven by preBötC inspiratory neurons synchronize the inspiratory and expiratory rhythms when AE is present. We will use an optogenetic approach in transgenic mice to selectively manipulate the inhibitory pathway from the preBötC to the pFL while monitoring the electrical activity of inspiratory and expiratory muscles. This original study will define the role of inhibitory projections from the preBötC to the pFL and how this interaction contributes to generating homeostatic respiratory responses during metabolic challenges. (AU)