Molecular mechanisms involved with the CO2/H+ sensitivity in the hypothalamus.

• Grant number: 22/15026-4
• Support Opportunities: Scholarships abroad - Research
• Start date: August 01, 2024
• End date: July 31, 2025
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Mirela Barros Dias
• Grantee: Mirela Barros Dias
• Host Investigator: Daniel Kent Mulkey
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Institution abroad: University of Connecticut (UCONN), United States

Abstract

Central chemoreception is an essential mechanism for detecting extracellular levels of CO2/H+ and triggering appropriate pulmonary ventilatory responses to correct these parameters. Chemosensitive neurons are located in many regions of the brain, and one of these areas is presumably the lateral hypothalamus (LH). The chemosensitive activity of this region has been attributed to orexinergic neurons, but it is not clear whether these neurons are indeed activated by CO2/H+ and the mechanisms involved in this response. Results from a previous study suggest that OX neurons are activated by CO2/H+, possibly through the inhibition of a background potassium channel (K2P). However, these experiments were conducted in an anoxic context. Since OX neurons appear to be inhibited by both normocapnic and hypercapnic hypoxia, it is clear there are many unanswered questions regarding the potential sensitivity of OX neurons to CO2/H+ and the possible mechanisms for O2 detection in the LH. Given that OX neurons project to important respiratory control centers, including the retrotrapezoid nucleus (RTN), and influence the hypercapnic ventilatory responses of these regions, it is important to definitively establish whether and how these cells contribute to the detection of CO2/H+ and O2. Therefore, the aim of this project is to investigate, at the cellular level, the CO2/pH chemosensitivity of the LH, particularly of orexinergic neurons, including the mechanisms involved not only in the detection of CO2/H+, but also O2, through in vitro electrophysiological recording protocols.