Understanding the basis of dyspnea and the mechanisms that produce apnea requires knowledge of the neural circuits that control the breathing rhythm. Currently, however, the neural mechanisms that are the basis for respiration are uncertain. The current investigative approach is primarily a reductionist one. This is based on the concept that the neural circuits involved can be unravelled if the component parts are identified as well as how they interact. The obvious difficulty of this approach leads to consideration of alternative strategies. One such approach is to develop an understanding of the evolution of the respiratory pattern generator by studying its behavior in more primitive species and then following its development. This has led other to extensive study of the pattern generator for gill ventilation in lampreys and fish. But there is no proof that the mammalian respiratory pattern generator and that for gill ventilation are related. The presence of both pulmonary and gill ventilation in species such as the lungfish challenge this concept. In preliminary studies it has been demonstrated that the response characteristics of the circuits controlling pulmonary ventilation in the lungfish have many of the same features as in mammals. Thus study of neural control of ventilation in this species seems a more appropriate starting point for investigation of the evoluntionary development of the respiratory pattern generator. An additional advantage of the species is that its central nervous system contains high concentrations of TRH thereby facilitating study of the role of this neuropeptide in respiratory neural control. Thus, the aims of this proposal are to establish the response characteristics of the pattern generators for both pulmonary and gill ventilation so as to relate these to those described for lamprey and mammals. The neural mechanisms mediating these rhythms will be studied by both extracellular recording of neuronal activity and by intracellular recording of synaptic input into respiratory motoneurons. This will permit concepts to be developed as to how respiratory rhythm is generated and serve as a focus for comparison to other species. The electro-physiology studies will be complimented by study of the role of TRH in respiratory rhythmogenesis. Neurophysiological results will be related to those from neuroanatomical studies on the distribution of receptors for TRH and TRH-containing neurons. The hypothesis that TRH mediates its effect on respiration by causing alterations in state will be studied by taking advantage of the natural state of dormancy - estivation.