Sympathetic nervous system and locomotor integration from V3 spinal neurons
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Approximately 80,000 individuals live with spinal cord injury (SCI) in Canada. Dysregulation of sympathetic function is common after SCI because communication between autonomic centres and spinal sympathetic outflow is lost due to the intervening injury. However, sympathetic preganglionic neurons (SPNs) located in the intermediate lamina (IML) of T1-L2 spinal cord (SC) retain spontaneous activity, and lumbar electrical stimulation appears to increase thoracic sympathetic output and cardiovascular function after cervical SCI. The source of this excitatory neuronal input to SPNs is unknown. We hypothesized that ascending propriospinal interneurons (INs) located in the lumbar SC synapse with and provide excitatory drive to thoracic SPNs (tSPNs). We tested our hypothesis examining innervation patterns from lumbar V3 INs on tSPNs in Sim1CreTdTomato mice. To characterize the distribution of V3 INs, we counted and determined soma location in transverse sections of thoracic and lumbar SC. To determine if lumbar V3 INs show distinct innervation patterns to tSPNs, BDA was injected near the central canal into L1-L5 segments. To investigate which V3 IN populations were responsible for input to T8 (mediating sympathetic output to adrenal glands), CTB was injected targeting the IML. One-week post-surgery, mice were euthanized, SCs were harvested and processed for immunohistochemistry. IMARIS Bitplane was used to generate and quantify 3-dimensional reconstructions of tSPNs and synaptic contacts. Of all excitatory VGlut2 input apposing tSPNs, ~20% arose from V3 IN projections (TdTom+/VGlut2+, n = 4 mice). L2 BDA injections resulted in 2x more contacts in T1-6 versus T7-T12, whereas L4/5 BDA injections resulted in 2.6x more contacts in T7-T12 (BDA+/TdTom+). Injections of CTB targeting T8 IML revealed that ipsilateral (74%, 55%, 63%) and contralateral (67%, 55%, 67%; V3D, V3intermediate, V3V respectively) V3 INs in L1-6 provided input to T8 (n = 4 mice). This is the first demonstration that spinal neurons involved in locomotion provide direct synaptic input to SPNs and may suggest locomotor function is intrinsically integrated with sympathetic autonomic functions at the level of the SC. In future, these findings may help direct spinal electrical stimulation studies aimed at improving not only locomotor function, but autonomic function and life quality in SCI individuals.
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