This proposal examines the central processing of pulmonary vagal afferent activity and the functioning of medullary and supramedullary structures in the neural control of ventilation. Studies are based primarily upon application of the 14C-2-deoxyglucose technique which provides quantitative information on changes in neural function of discrete areas of the brain in response to specific stimuli. The issue of a functional topographical organization of the nucleus tractus solitarius (NTS), the area of the first synapse of vagal afferents, including those from pulmonary mechanoreceptors, will be examined. In addition, analysis will be extended to other medullary and supramedullary areas with respect to this concept of functional topograpical organization. Stimulation of afferents will be effected electrically and mechanically. In the first study proposed we will investigate whether there is a different organization in the topography of the central projections of large myelinated afferents in the vagus and those that are non-myelinated. For those studies selective electrical stimulation of the vagus will be employed. We postulate that such a difference exists and explains apparently discordant data in the literature. We will then investigate which areas in both the medulla and supramedullary structures are activated by stimuli applied in the different phases of the respiratory cycle, since evidence indicates that there is gating of this afferent input; i.e. certain neural pathways are activated in only one phase of the respiratory cycle. Following studies with electrical vagal stimulation, we will employ a mechanical stimulus to determine the functional topography of the central connections of one specific afferent, that from pulmonary stretch receptors. This afferent input has an important role in respiratory control since it affects respiratory timing mechanisms and also the efferent activity to the respiratory muscles. In these studies we will examine the functional topography when mechanical stimuli are applied in either inspiration or expiration because of the gating phenomenon. Finally, studies will be done in animals in which lung disease is induced. Each disease state is one which is associated with dyspnea in man. Interpretation of these studies will depend heavily on the results from earlier studies employing stimulation of vagal afferents. The studies are intended to provide the functional and neuroanatomical foundations for a future quantitative evaluation of altered respiratory sensations in man.
