Monosynaptic Projections to Excitatory and Inhibitory preBotzinger Complex Neurons

The key driver of breathing rhythm is the preBotzinger Complex (preBotC) whose activity is modulated by various functional inputs, e.g., volitional, physiological, and emotional. While the preBotC is highly interconnected with other regions of the breathing central pattern generator (bCPG) in the brainstem, there is no data about the direct projections to either excitatory and inhibitory preBotC subpopulations from other elements of the bCPG or from suprapontine regions. Using modified rabies tracing, we identified neurons throughout the brain that send monosynaptic projections to identified excitatory and inhibitory preBotC neurons in mice. Within the brainstem, neurons from sites in the bCPG, including the contralateral preBotC, Botzinger Complex, the nucleus of the solitary tract (NTS), parafacial region (pF(L)/pF(V)), and parabrachial nuclei (PB), send direct projections to both excitatory and inhibitory preBotC neurons. Suprapontine inputs to the excitatory and inhibitory preBotC neurons include the superior colliculus, red nucleus, amygdala, hypothalamus, and cortex; these projections represent potential direct pathways for volitional, emotional, and physiological control of breathing.