Study of brain regions and neural mechanisms involved with respiratory responses in situations of hypercapnia during sleep and wakefulness

Abstract

Central chemoreception is a fundamental homeostatic mechanism and the dysfunction in its regulation, especially during sleep, has been related to several sleep-related respiratory diseases, which are present in an increasingly prevalent way in the current population. Evidence suggests that throughout the sleep-wake cycle there is a variation of central chemoreflex, as well as the predominance of the chemosensitive sites and neurochemical mechanisms involved, however such mechanisms are still little known. Thus, the present project proposes to study neurotransmitters (orexins, melatonin, MCH) and regions of the central nervous system classically involved in the control of the sleep-wake cycle such as the tegmental nucleus pontine peduncle (PPTg), or involved with respiratory disorders during sleep as is the case with the kölliker-fuse (KF) nucleus, which share functions in respiratory control and, possibly, have relevance in the control of the hypercapnic central chemoreflex. We will investigate the possible role of these neurotransmitters and brain regions in the modulation of respiratory control during activation of the central chemoreflex, during wakefulness and sleep. To do so, neuroanatomical and functional techniques will be used, including immunohistochemistry, microinjections, central microdialysis, pulmonary ventilation recordings in unanesthetized rats, EEG, EMG, body temperature as well as electrophysiological experiments, with patch-clamp technique. (AU)