RESEARCH INTERESTS: My primary research interests include the cellular and molecular characteristics of neurons involved in cardio-respiratory control and the mechanisms underlying neuronal sensitivity to gases (CO2, O2, and inert gases), hyperbaric pressure, acid-base disturbances and redox stress. Ongoing research in my laboratory focuses on understanding how redox stress (increased production of reactive oxygen and nitrogen species, ROS/RNS), hypercapnia and intracellular pH (pHi) interact and alter the electrophysiological properties of putative central CO2/H+-chemoreceptor neurons in the brainstems cardio-respiratory centers. Comparisons of neuronal sensitivity of cardio-respiratory neurons to hyperoxia, hypercapnia and redox stress are made with neurons in other CNS regions such as the CA1 hippocampus. This research has relevance to understanding normal and abnormal function in cardio-respiratory control, the central effects of episodic hypoxia and reoxygenation (e.g., disordered breathing or sleep apnea), and in understanding neurological problems arising from the use of oxygen (hyperoxia) in clinical medicine and combat operations. More recently, we have expanded our technical approach to include atomic force microscopy (AFM) as a research tool to identify how gases over a physiologically relevant range of pressures affects the plasma membrane and underlying cytoskeleton of neurons, which we predict is key to understanding the deleterious effects of hyperbaric gases on CNS function.

Technical approaches and methods commonly used in my lab include the followingelectrophysiological and fluorescence measurements of central neurons using in vitro (rat brain) animal preparations. Specific techniques include: whole-cell/perforated-patch recordings with patch-clamp micropipettes; intracellular recording with microelectrodes; intracellular dye injection and reconstruction of neuronal morphology; stereotaxic neurosurgery; immunohistochemistry; fluorescence/light microscopy; ratiometric fluorescence imaging of pHi and intracellular ROS/RNS in living tissue slices (brain slices); atomic force microscopy; polarographic measurements of tissue slice PO2, extracellular pH and ROS/RNS; and hyperbaric/hypobaric technology and methods: conducting intracellular recordings and measuring pHi and ROS/RNS from neurons in rat brain slices during compression and decompression and exposure to hyperbaric/hypobaric gases; hyperbaric atomic force microscopy; and whole-animal exposure to hyperbaric/hypobaric gases as a means of oxidative preconditioning. Currently, we are developing an in vivo animal model for studying cardio-respiration during changes in oxygen tension and barometric pressure.