A Latent Propriospinal Network Can Restore Diaphragm Function after High Cervical Spinal Cord Injury

作者：Cregg Jared M; Chu Kevin A; Hager Lydia E; Maggard Rachel S J; Stoltz Daimen R; Edmond Michaela; Alilain Warren J; Philippidou Polyxeni; Landmesser Lynn T; Silver Jerry^*

来源：Cell Reports, 2017, 21(3): 654-665.

DOI：10.1016/j.celrep.2017.09.076

Spinal cord injury (SCI) above cervical level 4 disrupts descending axons from the medulla that innervate phrenicmotor neurons, causing permanent paralysis of the diaphragm. Using an ex vivo preparation in neonatal mice, we have identified an excitatory spinal network that can direct phrenic motor bursting in the absence of medullary input. After complete cervical SCI, blockade of fast inhibitory synaptic transmission caused spontaneous, bilaterally coordinated phrenic bursting. Here, spinal cord glutamatergic neurons were both sufficient and necessary for the induction of phrenic bursts. Direct stimulation of phrenic motor neurons was insufficient to evoke burst activity. Transection and pharmacological manipulations showed that this spinal network acts independently of medullary circuits that normally generate inspiration, suggesting a distinct non-respiratory function. We further show that this "latent" network can be harnessed to restore diaphragm function after high cervical SCI in adult mice and rats.

• 出版日期2017-10-17