Abrupt neurotoxic destruction of >70% of the pre-Botzinger complex (preBotzC) in awake goats results in respiratory and cardiac failure (51). However, in reduced preparations, rhythmic respiratory activity has been found in other areas of the brainstem (15, 17, 19, 42); thus, we hypothesized that when the preBotzC is destroyed incrementally over weeks, time-dependent plasticity within the respiratory network will result in a respiratory rhythm capable of maintaining normal blood gases. Microtubules were bilaterally implanted into the presumed preBotzC of 7 goats. After recovery from surgery, studies were completed to establish baseline values for respiratory parameters. At weekly intervals, increasing volumes (in order 0.5, 1, 5, and 10uL) of ibotenic acid (IA) (50mM) were then injected into the preBotzC. All IA injections resulted in a tachypnea and dysrhythmia featuring augmented breaths, apneas, and increased breath-to-breath variation in breathing. In studies at night, apneas were nearly all central and occurred in the awake state. Breath-to-breath variation in breathing was greater (P < 0.05) during wakefulness than during NREM sleep. One week after the final IA injection, the breathing pattern, breath-to-breath variation, and arterial blood gases and pH were unchanged from baseline, but there was a 20% decrease in respiratory frequency and CO₂ sensitivity (P < 0.05), as well as a 40% decrease in the ventilatory response to hypoxia (P < 0.001). In subsequent histological analysis of the presumed preBotzC region of lesioned goats, it was determined that there was a 90% and 92% reduction from control goats in total and neurokinin-1 receptor neurons, respectively. Therefore, it was concluded that: 1) the dysrhythmic effects on breathing are state-dependent, and 2) after incremental, near total destruction of the presumed preBotzC region, time-dependent plasticity within the respiratory network provides a rhythm capable of sustaining normal arterial blood gases.