Elucidating Emotional Control of Breathing: Monosynaptic projections from the central amygdala to the preBötzinger complex

Breathing behaviour is subject to emotional regulation, but the underlying mechanisms remain unclear. Here, we demonstrate a direct relationship between the central amygdala, a major output hub of the limbic system associated with emotional brain function, and the brainstem preBötzinger complex, which generates the fundamental rhythm and pattern for breathing. Here, we show that the connection between these two sites is monosynaptic and inhibitory, involving GABAergic central amygdala neurons whose axonal projections act predominantly via ionotropic GABAA receptors to produce inhibitory postsynaptic currents in preBötzinger neurons. We also demonstrate that stimulation of the central amygdala slows breathing rhythm in vivo. This pathway may provide a mechanism to inhibit breathing in the context of “freezing” behavior to assess threats and plan defensive action. The existence of this pathway may further explain how epileptic seizures invading the amygdala cause long-lasting apnea, which can be fatal. These results elucidate a link between emotional brain function and the well established brainstem nucleus for breathing generation and control. The existence of this heretofore uncharacterized link may help explain survival-related behavior in mammals and pertains to human anxiety disorders. Lastly, it may explain the etiology of a rare but fatal seizure-related disorder.