17The brainstem pre-Bötzinger complex (preBötC) generates inspiratory breathing rhythms, but 18 which neurons comprise its rhythmogenic core? Dbx1-derived neurons may play the preeminent 19 role in rhythm generation, an idea well founded at perinatal stages of development but not in 20 adulthood. We expressed archaerhodopsin or channelrhodopsin in Dbx1 preBötC neurons in 21 intact adult mice to interrogate their function. Prolonged photoinhibition slowed down or stopped 22 breathing, whereas prolonged photostimulation sped up breathing. Brief inspiratory-phase 23 photoinhibition evoked the next breath earlier than expected, whereas brief expiratory-phase 24 photoinhibition delayed the subsequent breath. Conversely, brief inspiratory-phase 25 photostimulation increased inspiratory duration and delayed the subsequent breath, whereas 26 brief expiratory-phase photostimulation evoked the next breath earlier than expected. Because 27 they govern the frequency and precise timing of breaths in awake adult mice with sensorimotor 28 feedback intact, Dbx1 preBötC neurons constitute an essential core component of the 29 inspiratory oscillator, knowledge directly relevant to human health and physiology. 30
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