This project investigated the role of chemical sensing neurons in the brainstem which are crucial for normal regulation of breathing. These neurons are responsible for ‘respiratory chemoreception’ which is a bodily mechanism that stimulates breathing in response to elevated levels of carbon dioxide in the blood. Since they control breathing, these neurons (‘RTN neurons’) are crucial for life, however, the mechanisms that underlie their activity in health humans and determining what goes wrong in humans with respiratory disorders, remain to be clarified. The function of RTN neurons changes in respiratory disorders including sleep apnea, obesity hypoventilation syndrome, apnea of prematurity & chronic obstructive pulmonary disease. In respiratory disorders, chronic build-up of carbon dioxide in the bloodstream impairs breathing, and neurons are very sensitive to this build up, so they do not function as well in that environment. New knowledge about this ‘resetting’ of respiratory chemoreception will assist translational research into respiratory disorders & lead to advances in drug treatment. Considerable data has accumulated in the literature concerning neuropeptide neurotransmitters in central chemoreceptor function in mammals but much less is known about the roles of central neuropeptides on ventilatory regulation. Dr Kumar uses innovative & cutting-edge basic research techniques to refine neurobiological approaches & identify new neuronal breathing circuitry. To follow is a summary of research results according to the aims of the Project:
Aim 1 Results: A commercially available biomarker targeting technique called ‘RNAscope’ to characterise the location of Galanin receptors 1, 2 and 3 within a brainstem region called the respiratory pattern generator (RPG) was developed. RPG neurons control respiratory muscles including the diaphragm, to facilitate breathing.
Aim 2 Results: 5 brain regions (NTS, RTN, amygdala, preoptic area and hypothalamus) were identified that provide galaninergic projections to the ventral respiratory column. Out of these regions only the RTN was activated in response to acute hypercapnia.
Aim 3 Results: It was discovered that the galani protein is trafficked to the nerve terminals. Therefore, instead of investigating galanin levels in the RTN, galanin levels in neuronal populations that receive innervation by the RTN are currently being investigated. These include the VRC and the NTS; the results are currently being analysed.