Participation of the noradrenergic neurons of locus coeruleus in the central generation of inspiratory and expiratory activities in response to the activation of the central chemoreceptors of rats

Abstract

In rest conditions, inspiration is an active phenomenon while expiration is a passive phenomenon, that is, the activity of the abdominal expiratory muscles is not very expressive. Under conditions of metabolic challenges, such as conditions of increased CO2 partial pressure and [H +] in arterial blood (hypercapnia/acidosis), there is an increase in inspiratory activity and expiration becomes active, producing increases in the activity of the abdominal muscles (activation of central chemoreceptors). Locus Coeruleus (LC) contains noradrenergic neurons that increase their frequency of action potentials when exposed to high CO2/[H+] levels and communicate with brainstem respiratory neurons to make compensatory adjustments in lung ventilation during conditions of hypercapnia/acidosis. From this, the hypothesis of this project is that the noradrenergic neurons of the LC participate of the inspiratory response and the central generation of the active expiration in response to the activation of the central chemoreceptors. To test it, noradrenergic neurons from LC will be selectively acutely and reversibly silenced by the application of the insect alatostatin peptide after selective cell transfection of these neurons in rats with a lentiviral vector to express Drosophila inhibitory G protein coupled receptors for alatostatin. Using in situ preparations of rats, we will determine the contribution of the noradrenergic neuronal population of LC in the central generation of inspiratory and expiratory motor nerve activities under basal conditions and in response to the activation of central chemoreceptors using hypercapnia/acidosis, as well as to characterize the electrophysiological changes and the respiratory modulation of the noradrenergic neurons of LC. Therefore, the results to be obtained with this project can bring important information about the neural substrates involved in the generation and modulation of the central motor inspiratory and expiratory activities of rats. (AU)