Abstract
The broad distribution of serotonin (5-HT) in various organisms indicates that this is a phylogenetically ancient system. In the nervous system, 5-HT is involved in several functions, including circadian rhythms, diet, emotional state, control of sleep and respiratory control. In mammals, respiration is a rhythmic process, initiated in the central nervous system (CNS). At rest, expiration is a passive process, however, mammals recruit expiratory muscles (such as abdominal) under conditions of increased respiratory drive, such as during hypercapnia. Studying active expiration is critical, as it constitutes an important defense mechanism, activated under conditions essential to generate forced expiration. It also may be involved in pathological conditions. Studies have suggested that the RTN/pFRG is the main generator site of this activity. There are few studies on motor control and respiratory-related activity of the abdominal muscles (expiration), and there is no description of any other brainstem regions that may modulate this activity. In particular, medullary raphe 5-HT neurons, which are involved in the central CO2/pH chemoreception, since hypercapnia is a condition in which active expiration is present. The medullary raphe 5-HT neurons are considered to be an important component of CO2/pH chemoreception and through excitatory projections to RTN may influence and modulate active expiration. This type of serotonergic modulation on active expiration during hypercapnia has never been demonstrated, particularly in non-anesthetized animals and during sleep and wakefulness. In addition, the project will also address comparative aspects of 5-HT and respiratory control in vertebrates. In mammals, the role and involvement of 5-HT neurons in central chemoreception is well known. While this topic has been focused in mammals, few studies have been conducted in other vertebrate classes. Therefore, this project also aims to study the role of 5-HT neurons in the ventilatory response to hypercapnia, using two animal models: the lungfish (Lepidosiren paradoxa, known as Pirambóia) and birds (chicken, Gallus gallus). The evaluation of the involvement of 5-HT system in central chemoreception in these two classes of animals is unprecedented in the literature. All experiments will be performed in non-anesthetized animals and 5-HT receptors agonist and antagonist as well as specific chemical lesion of 5-HT neurons will be applied to test the involvement of 5-HT system on the respiratory variables proposed in the study presently. (AU)
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