A hallmark feature of the neural system controlling breathing is its ability to adapt through plasticity; a persistent change in system performance following a previous experience. Two well-studied models of respiratory plasticity are inactivity-induced phrenic motor facilitation (iPMF) and hypoxia-induced phrenic long-term facilitation (pLTF). To date, these forms of plasticity have only been studied independently — however, clinically relevant reductions in respiratory neural activity often occur with concomitant hypoxia. While intermittent neural apnea and intermittent hypoxia elicit plasticity in isolation, I demonstrate that concurrent induction of iPMF and pLTF constrains plasticity. Recent advancements have defined distinct signaling pathways for iPMF and pLTF, yet little is known of how intermittent neural apnea with hypoxia limit the capacity for respiratory plasticity; a phenomenon termed “dual stimulus cross-talk inhibition”. The purpose of this thesis was to define mechanisms giving rise to dual stimulus cross-talk inhibition in the control of breathing. Specifically, I describe how complex experiences may give rise to contending signaling cascades that undermine expression of respiratory plasticity. Further, I have identified several approaches for bypassing cross-talk inhibition, thus enabling compensatory respiratory plasticity for enhanced breathing control during central sleep apnea; a disease characterized by recurrent apneas/hypopneas with concomitant hypoxia. Advancing our understanding of how distinct experiences are encoded into interactive signaling networks is an important goal as we translate basic science discoveries into novel therapeutic strategies for incurable neural disorders.