Abstract
The key driver of breathing rhythm is the preBötzinger Complex (preBötC) whose activity is modulated by various functional inputs, e.g., volitional, physiological, and emotional. While the preBötC 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 preBötC 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 preBötC neurons in mice. Within the brainstem, neurons from sites in the bCPG, including the contralateral preBötC, Bötzinger Complex, the nucleus of the solitary tract (NTS), parafacial region (pFL/pFV), and parabrachial nuclei (PB), send direct projections to both excitatory and inhibitory preBötC neurons. Suprapontine inputs to the excitatory and inhibitory preBötC 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.
Highlights
Breathing is a remarkable behavior that sustains a robust and precisely modulated rhythmic movement appropriate across all behaviors and states, including for: (i) homeostatic regulation of blood gas and pH levels, (ii) volitional control of airflow for speech, breath-holding, etc., (iii) emotional control of airflow for laughing, crying, sighing, etc., and (iv) sleep and wakefulness
We found that within the brainstem, preBötzinger Complex (preBötC) neurons receive inputs from other brainstem breathing central pattern generator (bCPG) regions including contralateral preBötC, Bötzinger Complex, intermediate reticular region, the nucleus of the solitary tract (NTS), and parabrachial nuclei/Kölliker-Fuse (PB/KF)
We first identified a panel of regions that project to the preBötC using a non-genetic tracer, allowing us to subsequently focus on regions most likely to contain retrogradely labeled cells using the modified rabies strategy
Summary
Breathing is a remarkable behavior that sustains a robust and precisely modulated rhythmic movement appropriate across all behaviors and states, including for: (i) homeostatic regulation of blood gas and pH levels, (ii) volitional control of airflow for speech, breath-holding, etc., (iii) emotional control of airflow for laughing, crying, sighing, etc., and (iv) sleep and wakefulness. Substrates for such modulation are subpopulations of preBötC neurons that receive signals from regulatory brain centers such as the hypothalamus, which monitors and controls many important aspects of physiological state, e.g., temperature, arousal, and pregnancy, the limbic system related to emotional control of breathing, and cortical structures that control volitional movements that involve breathing, e.g., speech, breathholding. The regions of the brain that project to and innervate the preBötC have been broadly identified. Brain regions such as the lateral and paraventricular hypothalamus, the central amygdala, orbital cortex, and various raphe and brainstem nuclei, are sources of afferent projections to the bCPG (Gang et al, 1995). Retrograde tracers used in these studies were not specific to neuronal subtypes, e.g., excitatory vs. inhibitory neurons, and could have been taken up by fibers of passage that could underlie false positives, motivating the present study
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
