Grant: Operating Grant

In mammals, either direct or indirect perturbations of both peripheral and central respiratory control centres result in drastic breathing disturbances leading to cardiovascular and respiratory disorders (such as chronic obstructive pulmonary disease-COPD, heart failure, sudden infant death syndrome-SIDS, persistent hypertension etc). Despite recent advances in our understanding of neural and chemosensory basis of respiratory control, the fundamental mechanisms that regulate breathing remain however largely unknown. A number of questions regarding the identity, location and the organization of mammalian respiratory pattern generating neurons (CPG) and their chemosensory counterparts in both adults and newborns remain unanswered. In this context, our approach is to develop a simple model system where cellular and molecular mechanisms by which hypoxia modulates respiratory activity in both in vitro reconstructed networks and intact animals can be elucidated at the level of individual neurons. In our snail model system, we have not only identified CPG networks that control its respiratory behaviour, but also the peripheral chemosensory cells that regulate hypoxia-driven breathing. We will now use our novel brain-chip recording technologies to define mechanisms of neural control of respiration - from ion channels to single genes. This research would also help design future implantable, bionic devices for the respiratory dysfunction.