V2a neurons restore diaphragm function in mice following spinal cord injury

• 成果类型: Article
• 署名作者: Jensen, Victoria N.; Huffman, Emily E.; Jalufka, Frank L.; Pritchard, Anna L.; Baumgartner, Sarah; Walling, Ian; Gibbs, Holly C.; Mccreedy, Dylan A.; Alilain, Warren J.; Crone, Steven A.
• 署名单位: University System of Ohio; University of Cincinnati; University of Kentucky; University of Kentucky; Texas A&M University System; Texas A&M University College Station; Texas A&M University System; Texas A&M University College Station; Cincinnati Children's Hospital Medical Center; University System of Ohio; University of Cincinnati; Texas A&M University System; Texas A&M University College Station; Texas A&M University System; Texas A&M University College Station; Cincinnati Children's Hospital Medical Center; University System of Ohio; University of Cincinnati
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8880
• DOI: 10.1073/pnas.2313594121
• 发表日期: 2024-03-12
• 关键词: crossed-phrenic phenomenon; respiratory plasticity; genetic ablation; motor behaviors; RECOVERY; interneurons; reorganization; motoneurons; pathways; regeneration

摘要

The specific roles that different types of neurons play in recovery from injury is poorly understood. Here, we show that increasing the excitability of ipsilaterally projecting, excitatory V2a neurons using designer receptors exclusively activated by designer drugs (DREADDs) restores rhythmic bursting activity to a previously paralyzed diaphragm within hours, days, or weeks following a C2 hemisection injury. Further, decreasing the excitability of V2a neurons impairs tonic diaphragm activity after injury as well as activation of inspiratory activity by chemosensory stimulation, but does not impact breathing at rest in healthy animals. By examining the patterns of muscle activity produced by modulating the excitability of V2a neurons, we provide evidence that V2a neurons supply tonic drive to phrenic circuits rather than increase rhythmic inspiratory drive at the level of the brainstem. Our results demonstrate that the V2a class of neurons contribute to recovery of respiratory function following injury. We propose that altering V2a excitability is a potential strategy to prevent respiratory motor failure and promote recovery of breathing following spinal cord injury.