Medullary tachykinin precursor 1 neurons promote rhythmic breathing.

Rhythmic breathing is generated by neural circuits located in the brainstem. At its core is the preBötzinger Complex (preBötC), a region of the medulla, necessary for the generation of rhythmic breathing in mammals. The preBötC is comprised of various neuronal populations expressing neurokinin-1 receptors, the cognate G-protein-coupled receptor of the neuropeptide substance P (encoded by the tachykinin precursor 1 or ). Neurokinin-1 receptors are highly expressed in the preBötC and destruction or deletion of neurokinin-1 receptor-expressing preBötC neurons severely impair rhythmic breathing. Although, the application of substance P to the preBötC stimulates breathing in rodents, substance P is also involved in nociception and locomotion in various brain regions, suggesting that neurons found in the preBötC may have diverse functional roles. Here, we characterized the role of -expressing preBötC neurons in the generation of rhythmic breathing in vivo, as well as motor behaviors. Using a cre-lox recombination approach, we injected adeno-associated virus containing the excitatory channelrhodopsin-2 ChETA in the preBötC region of -cre mice. Employing a combination of histological, optogenetics, respiratory, and behavioral assays, we showed that stimulation of glutamatergic or preBötC neurons promoted rhythmic breathing in both anesthetized and freely moving animals, but also triggered locomotion and overcame respiratory depression by opioid drugs. Overall, our study identified a population of excitatory preBötC with major roles in rhythmic breathing and behaviors.