Astrocytic modulation on brainstem neurons involved with generation and control of sympathetic and respiratory activities in rodents submitted to hypoxia

Abstract

The main goal of this Thematic Project is to study the astrocytic modulation on the synaptic transmission of neurons integral to sympathetic and respiratory networks at the brainstem level under normoxic as well as in hypoxic conditions. This important and contemporary topic in the literature is associated to the role of astrocytes and their gliotransmitters on the modulation of synaptic transmission in neuronal networks of autonomic and respiratory functions located at the nucleus tractus solitary (NTS) and in the neurons located in the ventral medulla in charge of generation of sympathetic activity (RVLM) and the respiratory rhythm and pattern (Botzinger and pre-Botzinger complexes). Due to technical and methodological challenges to explore the interaction between the components of the tripartite synapse under physiological conditions, we will use the strategy of inhibition or activation of astrocytes by hypoxia protocols in order to reveal the possible and expected modulation of astrocytes on the synaptic transmission in neurons integral to the sympathetic and respiratory networks at the brainstem of rats and mice. We will use simultaneous electrophysiological recordings (patch-clamp) and real time functional images as well as cellular, molecular biology and genetics approaches. Experiments will be performed in rats as well as in mices. The use of genetically modified mices will allow us a better evaluation of the communication in between astrocytes and neurons. All information to be generated by the experiments proposed for this Thematic Project will be really important for a better understanding of the mechanisms underlying the cardiovascular and respiratory changes observed under hypoxic challenges such as obstructive sleep apnea, heart failure, stroke, and chronic pulmonary diseases. (AU)