Our major objective is to enhance understanding of the control of breathing. A related objective is to gain insight into mechanisms which determine O2 transport during exercise. The 1st specific aim is to determine whether afferents from exercising limbs are critical to the exercise hyperpnea. In pilot studies under anesthesia, the ventilatory (V-E) response to electrically induced exercise was attenuated by lesioning the dorsal lateral sulcus (DLS) & dorsal lateral funiculus (DLF) spinal pathways at the L2 level. Except for the 1st of 4 dogs & the 1st of 2 ponies, lesioning did not compromise ambulation. Accordingly, during treadmill exercise, V-E and blood gases will be studied in 8 awake ponies before and 2-4 weeks after DLS and DLF lesions or sham surgery. A 2nd aim is to determine whether spinal lesioning in carotid body denervated (CBD), hilar nerve denervated (HND), and CBD+HND ponies affects the exercise hyperpnea differently than spinal lesions alone. Studies before and after multiple lesions are a means of testing the hypothesis that multiple mechanisms are capable of mediating the exercise hyperpnea, and therefore the hyperpnea may not be attenuated unless most or all mechanisms are eliminated. A 3rd aim is to test the hypothesis that breathing periodicity at high altitude is due to the increased carotid chemoreceptor gain due to hypoxia combined with the hypocapnia-induced apnea threshold. Breathing, blood gases, and EEG will be monitored in 8 ponies before and after CBD or sham CBD in awake and sleeping states at sea level and during 3 days of hypobaria (PaO2 = 40 mmHg). A 4th aim is to determine whether upper airway, lung, or carotid sensory mechanisms alter respiratory neural output to defend tidal volume when inspiratory muscle length is altered to an unfavorable portion of the length-tension curve. V-E, blood gases, and respiratory muscle EMG will be studied in normal, CBD, HND, and tracheostomized ponies before and during positive pressure breathing (+10CM H2O) which increases lung volume and alters muscle length. A 5th aim is to determine whether the 25% overshoots in heart rate and cardiac output of ponies in the 1st min of work are due to mobilization of splenic erythrocytes or peripheral afferent information. These responses will thus be studied before and after DLS and DLF spinal lesions and in other ponies before and after splenectomy. The pony is a proven model for chronic studies requiring maintenance of physiologic conditions. Accordingly, use of the awake pony provides unique tests of theoretical models and hypotheses developed using other species under conditions of anesthesia.