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- Title
Thoracic VGluT2<sup>+</sup> Spinal Interneurons Regulate Structural and Functional Plasticity of Sympathetic Networks after High-Level Spinal Cord Injury.
- Authors
Noble, Benjamin T.; Brennan, Faith H.; Yan Wang; Zhen Guan; Xiaokui Mo; Schwab, Jan M.; Popovich, Phillip G.
- Abstract
Traumatic spinal cord injury (SCI) above the major spinal sympathetic outflow (T6 level) disinhibits sympathetic neurons from supraspinal control, causing systems-wide "dysautonomia." We recently showed that remarkable structural remodeling and plasticity occurs within spinal sympathetic circuitry, creating abnormal sympathetic reflexes that exacerbate dysautonomia over time. As an example, thoracic VGluT2+ spinal interneurons (SpINs) become structurally and functionally integrated with neurons that comprise the spinal-splenic sympathetic network and immunological dysfunction becomes progressively worse after SCI. To test whether the onset and progression of SCI-induced sympathetic plasticity is neuron activity dependent, we selectively inhibited (or excited) thoracic VGluT2+ interneurons using chemogenetics. New data show that silencing VGluT2+ interneurons in female and male mice with a T3 SCI, using hM4Di designer receptors exclusively activated by designer drugs (Gi DREADDs), blocks structural plasticity and the development of dysautonomia. Specifically, silencing VGluT2+ interneurons prevents the structural remodeling of spinal sympathetic networks that project to lymphoid and endocrine organs, reduces the frequency of spontaneous autonomic dysreflexia (AD), and reduces the severity of experimentally induced AD. Features of SCI-induced structural plasticity can be recapitulated in the intact spinal cord by activating excitatory hM3Dq-DREADDs in VGluT2+ interneurons. Collectively, these data implicate VGluT2+ excitatory SpINs in the onset and propagation of SCI-induced structural plasticity and dysautonomia, and reveal the potential for neuromodulation to block or reduce dysautonomia after severe high-level SCI.
- Subjects
SPINAL cord injuries; INTERNEURONS; DESIGNER drugs; SPINAL cord; DYSAUTONOMIA
- Publication
Journal of Neuroscience, 2022, Vol 42, Issue 17, p3659
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.2134-21.2022