In this paper, we are the first to show at early stages of disease in a mouse model of ALS, the mice use accessory respiratory muscles, but that they are not activated at late stages of disease when ventilation begins to decline. Further, we demonstrate that one particular class of neuron in the spinal cord and brainstem (the V2a class) are able to activate accessory respiratory muscles in healthy mice, but degenerate in ALS model mice. Our results suggest that therapies to prevent V2a degeneration or replace V2a neurons may improve breathing and motor function in ALS patients.