Control of the respiratory rhythm and chemosensitivity by the brainstem: role of molecular, cellular and physiopathology aspects

• Grant number: 21/05299-0
• Support Opportunities: Research Projects - Thematic Grants
• Start date: December 01, 2024
• End date: November 30, 2029
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Thiago dos Santos Moreira
• Grantee: Thiago dos Santos Moreira
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Ana Carolina Thomaz Takakura ; Bárbara Falquetto ; Davi José de Almeida Moraes ; Vagner Roberto Antunes
• Associated research grant(s): 24/23158-3 - Multi-user equipment approved in grant 2021/05299-0: Confocal Fluorescence Microscope, AP.EMU

Abstract

Breathing automatism and the chemical control of respiration are inseparable processes. The parafacial respiratory group (pFV) constitutes a group of excitatory neurons expressing the transcription factor Phox2b and plays a relevant role in the central chemoreception process (retrotrapezoid nucleus neurons - RTN) and respiratory automatism. The pFV is also regulated by afferent information from peripheral chemoreceptors and various neuromodulatory synaptic inputs from other brain nuclei such as the hypothalamus. Thus, pFV neurons are involved in modulating the rhythm and pattern of respiration (inspiration and expiration), controlling the activity of neurons located in the ventrolateral bulb respiratory column. Our research group has been investigating how pFV neurons alter their activity in response to various received neuromodulatory interactions, thus influencing respiratory control (Moreira et al., 2021).Oxytocinergic signaling plays an important role in maintaining physiological functions, including respiration. However, the involvement of oxytocinergic signaling in modulating the activity of pFV neurons impacting respiratory control has not yet been investigated and is the main objective of this project.Therefore, in this project, we propose to investigate how oxytocinergic signaling can modulate the activity of pFV neurons and contribute to respiratory control. To achieve this, we propose the use and implementation of new experimental techniques that will allow us to understand from cellular components to the integrative physiology of oxytocinergic signaling in the parafacial respiratory region. Basically, we will use a technology based primarily on the use of neurotropic viruses, genetically modified animals, and recordings of the electrical activity of neuronal populations. By combining these methodologies with a repertoire of neuroanatomical and neurophysiological methods, we propose the following objectives:Study the origin of oxytocinergic projection to the parafacial respiratory region.Investigate whether there is a difference in oxytocinergic signaling to the parafacial respiratory region relative to sexual dimorphism.Characterize the synaptic action of oxytocin on neuronal cells in the parafacial respiratory region.Characterize the synaptic action of oxytocin on non-neuronal cells (glial cells) in the parafacial respiratory region.Study the possible mechanism by which oxytocinergic signaling, acting in the parafacial respiratory region, could improve clinical conditions of respiratory depression.Investigate the involvement of oxytocinergic pathways to the parafacial respiratory region in the control of the sleep-wake cycle. (AU)