Central amygdala-to-pre-Bötzinger complex neurotransmission is direct and inhibitory

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 pre-Bötzinger complex, which generates the fundamental rhythm and pattern for breathing. The connection between these two sites is monosynaptic and inhibitory, involving GABAergic central amygdala neurons whose axonal projections act predominantly via ionotropic GABA_A receptors to produce inhibitory postsynaptic currents in pre-Bötzinger neurons. This pathway may provide a mechanism to inhibit breathing in the context of freezing 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. Although their ultimate importance awaits further behavioural tests, these results elucidate a link between emotional brain function and breathing, which underlies survival-related behaviour in mammals and pertains to human anxiety disorders.