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

Central chemoreception is a fundamental homeostatic mechanism by which the brain detects even the most subtle changes in tissue pCO2/pH and promotes the necessary regulatory adjustments to ensure maintenance of the acid-base balance. Dysfunction in its regulation, especially during sleep, has been related to several sleep-related respiratory pathologies, which are increasingly prevalent in the current population. Central chemoreceptors are widely distributed throughout the brain, and the contribution of each chemosensitive site or the relative importance of each region in situations of hypercapnia seems to be variable, depending on the state of alert as well as other physical or behavioral conditions. In fact, evidence suggests that throughout the sleep-wake cycle there is a variation of the central chemoreflex, as well as the predominance of chemosensitive sites and neurochemical switches involved, however such mechanisms are still poorly known. Thus, the present project had as its general objective to study the participation of suprabulbar regions in the control of the hypercapnic ventilatory response, and to provide unprecedented information on the neural switches underlying the control of the central chemoreflex during the sleep-wake cycle. Therefore, the objectives of this project were: 1) To investigate the possible participation of melatonin in the lateral hypothalamus and perifornital area (LH/PFA) in the modulation of CO2 chemosensitivity and hypercapnic ventilatory response during the sleep-wake cycle. 2) To study the possible role of melanin-concentrated hormones (MCH) in the Lateral Hypothalamus/Perifornitial Area and in the Locus Coeruleus in modulating the ventilatory response to hypercapnia during sleep and wakefulness. 3) To investigate whether melatonin and MCH are involved in body temperature control during central chemoreflex activation during sleep and wakefulness. 4) Evaluate the role of orexinergic neurotransmission in the nucleus tractus solitarius (NTS) and in the nucleus tegmental peduncle pontine (PPTg) on breathing under conditions of normocapnia and hypercapnia during sleep and wakefulness.

For this purpose, we used techniques such as microinjections in the CNS, reverse central microdialysis, recording of pulmonary ventilation, EEG, EMG and body temperature in non-anesthetized Wistar rats.