Spinal interneurons (SpINs) are pivotal to the function of neural circuits, orchestrating motor, sensory, and autonomic functions in the healthy, intact central nervous system. These interneurons (INs) are heterogeneous, with diverse types contributing to various neural systems, including those that control respiratory function. Research in the last few decades has highlighted the complex involvement of SpINs in modulating motor control. SpINs also partake in motor plasticity by aiding in adapting and rewiring neural circuits in response to injury or disease. This plasticity is crucial in the context of spinal cord injury (SCI), where damage often leads to severe and long-term breathing deficits. Such deficits are a leading cause of morbidity and mortality in individuals with SCI, emphasizing the need for effective interventions. This review will focus on SpIN circuits involved in the modulation of breathing and explore current and emerging approaches that leverage SpINs as therapeutic targets to promote respiratory recovery following SCI.

The rhythm for each breath is generated by a specialized brainstem region called the preBötzinger complex. Many brain areas influence this region, but the sources of these inputs—and whether they excite or inhibit breathing—have not been systematically mapped. Here, we present an atlas identifying where excitatory and inhibitory signals to the preBötzinger complex arise across the mouse brain, providing a framework for understanding how breathing is shaped by sensory signals, behavior, and brain state.