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 plastici...