? ? This proposal describes a 5-year training program to develop an academic career in the field of developmental respiratory neurobiology as it pertains to respiratory control. The program provides a unique opportunity to build on the principal investigator's clinical expertise and to combine structured learning, course work and laboratory techniques into a multidisciplinary approach to studying immaturity of respiratory control. Dr. Richard Martin who will mentor the PI's scientific progress is a recognized leader in the field of neonatal apnea and control of breathing. He is the Head of the Division of Neonatology and has trained numerous fellows and graduate students. To enhance the training, the program will enlist the expertise of an advisory committee that consists of established investigators with extensive experience in applying physiology, immunohistochemistry, and retrograde tracing techniques to identify the neural pathways involved in control of breathing. The advisory committee will provide guidance and oversee the training of the PI during the proposed application. ? ? Recent work of the PI has characterized the involvement of gamma-Aminobutyric acid (GABA) in apnea induced through stimulation of the superior laryngeal nerve (SLN). The neural pathway(s) that mediate this reflex has not been established. We hypothesize that stimulation of the SLN activates specific GABAergic pathways that are key to the generation of reflex apnea in early life.
The specific aims of this proposal are to identify: 1) the inspiratory neurons inhibited, 2) the GABAergic neurons activated during SLN stimulation, and 3) to characterize the expression of GABAA receptors on inspiratory neurons. The proposed studies will entail medullary microinjection of GABAA receptor blockers to identify the inspiratory region inhibited through release of GABA during SLN stimulation. We will also identify the GABAergic neurons that project to these inspiratory neurons using c-fos expression and retrograde tracing, and characterize the expression of GABAA receptor subunits on inspiratory neurons using labeling and molecular techniques. ? ? The Pediatric Department at Case Western Reserve University provides an ideal setting for the training of physician-scientists by incorporating multidisciplinary expertise into customized programs. Such an environment maximizes the potential for the PI to establish an independent academic career. ? (End of Abstract) ? ? ? ?
| Abu-Shaweesh, Jalal M (2007) Activation of central adenosine A(2A) receptors enhances superior laryngeal nerve stimulation-induced apnea in piglets via a GABAergic pathway. J Appl Physiol 103:1205-11 |
