Medullary GABAergic Neurons Constitute a Neural Brake Coordinating Respiratory Rhythm In Vivo
Year: 2026
Type: article
Abstract: Motor behaviors, such as walking and breathing, depend on neural circuits combining excitatory and inhibitory neurons to produce rhythmic motor activities. Breathing is a critical autonomic motor function that requires excitatory and inhibitory circuits to orchestrate inhalation and exhalation. Inspiration is produced by excitatory medullary neurons of the preBötzinger complex (preBötC), a small region of the ventral medulla dedicated to breathing. Expiration is characterized by passive recoil of the lungs and thorax and is a critical phase of the respiratory cycle allowing air to be exhaled until the next inspiration happens. The brain circuits regulating the timing and pattern of expiration and determining when the next inspiration is produced have not been identified. Here, we propose that inhibitory gamma-aminobutyric acid (GABA)-ergic preBötC neurons act as a neural brake to prevent the next inspiration to be produced until expiration is fully completed. Using optogenetic tools to modulate GABAergic neurons in male and female mice in vivo, we showed that photostimulation of GABAergic preBötC neurons prevented the next inspiration to occur and considerably prolonged expiration. On the other hand, photoinhibition of GABAergic neurons quickly produced inspiration therefore aborting expiration. Collectively, GABAergic preBötC neurons are pivotal in orchestrating the transition from expiration to inspiration to properly complete exhalation. Importantly, understanding inhibitory circuits in the context of rhythmic breathing may be relevant to comprehend the universal properties of other rhythmic motor behaviors, such as walking, that also require alternating motor activity.
Source: Journal of Neuroscience
Institutions: St. Michael's Hospital, University of Toronto
Language: English
Subfield: Endocrine and Autonomic Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W7204070302