Role of olfactory sensory neurons in the ventilatory response to central chemoreflex activation

• Grant number: 22/11927-7
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2025
• End date: August 31, 2027
• 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 Takakura Moreira ; Bárbara Falquetto

Abstract

This project aims to investigate the functional involvement of the olfactory bulb (MOB) and olfactory sensory neurons in ventilatory responses to hypercapnia. Evidence suggests that the MOB, in addition to displaying an oscillatory rhythm coherent with respiration, may modulate respiratory activity through its connections with nuclei involved in ventilatory control. In Protocol 1, we propose selective optogenetic stimulation of glutamatergic neurons in the MOB to assess their effects on ventilation. In Protocol 2, we will use the anterograde tracer PHA-L to verify the existence of direct or indirect projections from the MOB to the ventral respiratory column, including the RTN/pFRG and the pre-Bötzinger complex. In Protocol 3, we will perform calcium imaging to analyze the activity of olfactory sensory neurons in response to different levels of CO¿ and odorants, with and without carbonic anhydrase inhibition. In Protocol 4, we will evaluate the ventilatory response to hypercapnia after pharmacological blockade of olfactory sensory neurons and the olfactory epithelium. Finally, in Protocol 5, we propose optogenetic inhibition of GABAergic projections from the basal forebrain to the MOB to investigate their role in modulating baseline ventilation and the ventilatory response to CO¿. Using neuroanatomical and neurofunctional approaches in genetically modified mice, this study seeks to elucidate underexplored mechanisms in the integration between olfactory chemoreception and respiratory control, contributing to a better understanding of the neural pathways involved in respiratory homeostasis. (AU)