Cervical spinal V2a neurons pattern respiratory muscle activity and enhance ventilation

Our prior studies suggested that one subset of V2a neurons activates accessory respiratory muscles whereas another subset of V2a neurons actively prevents their activation at rest. However, since these studies altered V2a neuron excitability throughout the spinal cord and brainstem, it was not clear whether the V2a neurons that activate accessory respiratory muscles are located in the same region of the neuraxis as V2a neurons that prevent activation of accessory respiratory muscles at rest. Therefore, we used a Cre‐dependent AAV virus injected into a Chx10 Cre/+ mouse to selectively target either the excitatory (G q )‐ or inhibitory (G i )‐DREADD receptor to cervical spinal V2a neurons on one side or both sides of the cord in order to alter V2a neuron excitability. Whole breath plethysmography (WBP) and electromyography (EMG) were recorded in conscious mice at rest to measure ventilation and respiratory muscle activity before and after altering V2a neuron excitability. We found that bilaterally increasing the excitability of cervical spinal V2a neurons increases accessory respiratory muscle (scalene) activity, diaphragm EMG peak amplitude, and ventilation. Although V2a neurons project ipsilaterally, increasing their excitability on one side of the cord is able to synchronously activate scalene muscles on both sides of the body. Bilaterally silencing cervical spinal V2a neurons also activates scalene muscle activity, but does not impair diaphragm function. Our results are consistent with the hypothesis that one subset of V2a neurons in the cervical spinal cord activates accessory respiratory muscles whereas another subset of cervical V2a neurons inhibits accessory respiratory muscles at rest. Support or Funding Information 1RO1NS112255T32NS5007453University of Cincinnati Dean’s Dissertation Completion Fellowship