Neural mechanisms involved in expiratory rhythm generator: possible involvement of the retrotrapezoid nucleus and the parafacial region

Abstract

The eupnoeic pattern of respiration consists of three phases: inspiration, post-inspiration (passive expiration, stage 1) and stage 2 of expiration. These studies demonstrated that, during respiration, phasic discharges are generated within the ventral respiratory column without the need for peripheral feedback, involving a neuronal network co-ordinated by synaptic interactions (Smith and cols., 1991) that was called ventral respiratory column. Moreover the neural mechanisms for respiratory control are carefully organized by a complex neuron system localized into the medulla oblongata. This system is highly sensitive to CO2 and maintains the CO2 and O2 in the blood into physiological level, controlling the ventilation cycle by cycle. During breathing at rest, air is expired passively by recoil forces. Augmenting expiratory activity during the second phase of expiration (E2) is always present in the brainstem during eupnoea. An expressed phasic expiratory activity in this motor outflow is observed only during increased ventilatory demand such as during exercise in man (Abraham and cols., 2002), hipercapnia or hypoxia in the cat (Fregosi and Bartlett, 1988, Fregosi, 1994, Iizuka and Fregosi, 2007). The origins and mechanisms of generation of this late expiratory activity remain poorly understood and several currently proposed concepts appear controversial. This question constitutes in one of the aims of this project. Recent evidences suggest the involvement of chemosensitive neurons of the retrotrapezoid nucleus (RTN) in the control of expiratory activity of premotor neurons of the caudal ventral respiratory group. In this way, it is important to investigate a real connection between RTN and the caudal ventral respiratory group neurons and, if it really exists, what are the physiological conditions in which such pathway emerges. In this study, we will use anatomical and electrophysiological approaches to investigate the existence of a projection from RTN to caudal ventral respiratory group neurons and the phenotype of the neurotransmitters involved in this projection. We also will study the involvement of the RTN neurons on the activation of caudal ventral respiratory group neurons. (AU)