Astrocytic modulation on brainstem neurons involved with generation and control of...
| Grant number: | 19/11863-6 |
| Support type: | Regular Research Grants |
| Duration: | February 01, 2020 - January 31, 2022 |
| Field of knowledge: | Biological Sciences - Biophysics - Cellular Biophysics |
| Principal Investigator: | Davi José de Almeida Moraes |
| Grantee: | Davi José de Almeida Moraes |
| Home Institution: | Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil |
Abstract
The parasympathetic efferent innervation to the respiratory system controls mainly the contraction of the smooth muscle and mucous secretion in the lower airways. It is well known that the parasympathetic pre-ganglionic motoneurons, that project to the respiratory system, are found in the medulla, specifically in the Nucleus Ambiguus (NA) and in the Dorsal Motor Nucleus of the Vagus (DMV). The parasympathetic activity for the respiratory system is also modulated by sensorial neurons located throughout the respiratory airways, and such vagal afferences are transmitting information related the physical and chemical conditions of the airways and lungs to the central nervous system. However, our understanding of how vagal afferences are processed and integrated into the brainstem leading to respiratory changes (bronchospasm and mucous secretions) required for cough and dyspnea remains limited. Furthermore, it is not clear what are the neurotransmitters and cellular mechanisms underlining the central generation of parasympathetic activity to the bronchi by NA and DMV motoneurons in response to vagal afferent stimulation. The study of these mechanisms is critical considering that the symptoms of the most common respiratory diseases (viral infections of the respiratory tract, rhinitis, bronchitis, asthma, COPD, chronic cough) are a consequence of changes in the nervous system. Thus, in order to improve our understanding of central cellular mechanisms involved in these pathological conditions, it is necessary to describe how motoneurons in the brainstem integrate the vagal sensorial afferences and control vagal motor bronchoconstrictor responses. For this purpose, we will apply the whole cell patch clamp technique, retrograde labelling and genetic manipulation (optogenetics) on brainstem slices and on in situ preparations from rats to evaluate: I) the electrophysiological properties of the DMV parasympathetic bronchial motoneurons, with emphasis on the control of their resting membrane potential and cellular excitability; II) how DMV parasympathetic bronchial motoneurons integrate the spontaneous synaptic transmission, that evoked by the stimulation of vagal afferents, and the neurotransmitters involved, and III) what is the role of DMV parasympathetic motoneurons in the control of lower airway resistance. The elucidation of these electrophysiological properties can promote a greater understanding about the cellular mechanisms involved in the central generation of the parasympathetic activity to the bronchi under physiological and pathological conditions, and even in the development of possible therapies aimed at the treatment of pathologies associated with dysfunctions in the afferent and efferent control of lower airways. (AU)