A Latent Propriospinal Network Can Restore Diaphragm Function after High Cervical Spinal Cord Injury
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A Latent Propriospinal Network Can Restore Diaphragm Function after High Cervical Spinal Cord Injury. / 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.
In: Cell Reports, Vol. 21, No. 3, 17.10.2017, p. 654-665.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - A Latent Propriospinal Network Can Restore Diaphragm Function after High Cervical Spinal Cord Injury
AU - Cregg, Jared M
AU - Chu, Kevin A
AU - Hager, Lydia E
AU - Maggard, Rachel S J
AU - Stoltz, Daimen R
AU - Edmond, Michaela
AU - Alilain, Warren J
AU - Philippidou, Polyxeni
AU - Landmesser, Lynn T
AU - Silver, Jerry
N1 - Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.
PY - 2017/10/17
Y1 - 2017/10/17
N2 - Spinal cord injury (SCI) above cervical level 4 disrupts descending axons from the medulla that innervate phrenic motor 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.
AB - Spinal cord injury (SCI) above cervical level 4 disrupts descending axons from the medulla that innervate phrenic motor 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.
KW - Animals
KW - Animals, Newborn
KW - Cervical Vertebrae/physiopathology
KW - Diaphragm/innervation
KW - Interneurons/pathology
KW - Light
KW - Lumbar Vertebrae/physiopathology
KW - Mice
KW - Motor Neurons/pathology
KW - Nerve Net/physiopathology
KW - Paralysis/physiopathology
KW - Phrenic Nerve/physiopathology
KW - Respiration
KW - Spinal Cord Injuries/physiopathology
KW - Synaptic Transmission/physiology
KW - Thoracic Vertebrae/physiopathology
U2 - 10.1016/j.celrep.2017.09.076
DO - 10.1016/j.celrep.2017.09.076
M3 - Journal article
C2 - 29045834
VL - 21
SP - 654
EP - 665
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 3
ER -
ID: 248114012