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Hypothalamus and retrotrapezoid nucleus interaction in the control of breathing activity

Grant number: 20/08620-1
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): November 01, 2020
Effective date (End): August 31, 2024
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal researcher:Thiago dos Santos Moreira
Grantee:Emmanuel Veríssimo de Araújo
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

The hypothalamus is a region involved in the functioning of several systems essential for the maintenance of life. A series of studies have demonstrated that hypothalamic regions, especially the paraventricular nucleus of the hypothalamus (PVH) project into fundamental regions of ventilatory control, such as the ventral respiratory column (VRC), the nucleus of the solitary tract (NTS) and the retrotrapezoid nucleus (RTN). In addition, it is known that PVH and RTN participate in the response of the peripheral chemoreflex, but it is not clear what the real interaction between PVH and RTN is in respiratory control. Here, the objective of the present study will be to investigate the interaction between PVH and RTN on ventilatory parameters in mice under baseline conditions or during hypoxic and hypercapnic challenges. We will use two strains of mice: a) Phox2b-Cre that expresses Cre recombinase in Phox2b neurons and b) control animals C57B6/J. Initially, CAV-2 adenovirus will be injected into the RTN of all mice used in this work, thus inducing the expression of Cre recombinase in the Phox2b-cre animals, which will reveal which hypothalamic neurons interact monosynaptically with the RTN. The next step will be to inject viral vectors (pAAV-hSyn-DIO-hM3D (Gq) -mCherry) or (pAAV-hSyn-DIO-hM4D (Gi) -mCherry) into the PHV region, which selectively induces receptor expression coupled to Gq or Gi protein. After a few days, the animals will be submitted to ventilatory recordings in a plethysmographic chamber and will receive an injection of clozapine that will activate the G protein pathways and reveal whether the activation or inhibition of the PVH-RTN pathway affects the ventilatory parameters under the hypercapnic or hypoxic challenge. Our hypothesis is that PVH neurons that project into the RTN region impact baseline respiratory activity and also during challenges such as hypoxia and hypercapnia. (AU)

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