Acute perturbation of Pet1- neuron activity in neonatal mice impairs cardiorespiratory homeostatic recovery

Cardiorespiratory recovery from apneas requires dynamic responses of brainstem circuitry. One implicated component is the raphe system of -expressing (largely serotonergic) neurons, however their precise requirement neonatally for homeostasis is unclear, yet central toward understanding newborn cardiorespiratory control and dysfunction. Here we show that acute in vivo perturbation of neuron activity, via triggering cell-autonomously the synthetic inhibitory receptor hM4D , resulted in altered baseline cardiorespiratory properties and diminished apnea survival. Respiratory more than heart rate recovery was impaired, uncoupling their normal linear relationship. Disordered gasp recovery from the initial apnea distinguished mice that would go on to die during subsequent apneas. Further, the risk likelihood of apnea-related mortality associated with suppression of neurons was higher for animals with baseline elevated ventilatory equivalents for oxygen. These findings establish that neurons play an active role in neonatal cardiorespiratory homeostasis and provide mechanistic plausibility for the serotonergic abnormalities associated with SIDS.