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Role of OLIG3 transcription factor on ventilatory responses to hypoxia and hypercapnia

Grant number: 17/10242-2
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): June 01, 2017
Effective date (End): May 31, 2018
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Thiago dos Santos Moreira
Grantee:Marina Yumi Shimada
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:15/23376-1 - Retrotrapezoid nucleus, respiratory chemosensitivity and breathing automaticity, AP.TEM

Abstract

Breathing automaticity and chemoreception are inseparable neural processes. The retrotrapezoid nucleus (RTN), a group of glutamatergic neurons that express the transcription factor Phox2b, may be a crucial nodal point through which breathing automaticity is regulated to maintain CO2 constant. Additional evidence that RTN neurons have central respiratory chemoreceptor properties is presented, but this is only one of many factors that determine their activity. The RTN is also regulated by powerful inputs from the carotid bodies and, at least in the adult, by many other synaptic inputs. It is also established that RTN neurons may control the activity of the downstream central respiratory pattern generator. Specifically, RTN neurons (a) innervate the entire ventral respiratory column and (b) control both inspiration and expiration. Based on the information above, this project will intend to analyze the role of RTN chemoreceptors neurons in the control of breathing under physiological, pathological and during development in mammals. To address this theory, we propose to use and to implement new techniques that will enable us to stimulate neurons in the brainstem selectively in both anesthetized and unanesthetized rats and mice. This new technology will be primarily based on the use of neurotropic viruses that will be engineered with a synthetic promoter in order to target light or ligand-activated receptors. By combining this methodology with mouse genetics and a repertoire of more traditional neuroanatomical and neurophysiological methods (AU)