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bioRxiv · 10.1101/2023.04.06.535901

Lumbar locomotor-related V3 interneurons provide direct excitatory synaptic input onto thoracic sympathetic preganglionic neurons

Chacon, C.·Nwachukwu, C. V.·Shahsavani, N.·Cowley, K. C.·Chopek, J. W.
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Abstract

Spinal cord injury (SCI) is a life-altering event causing sensation loss, motor paralysis and impaired autonomic function. Electrical spinal cord stimulation has shown promise for restoring lost motor, and impaired autonomic function, despite targeting lumbar locomotor networks. Sympathetic preganglionic neurons (SPNs), primarily located in the intermediate laminae of thoracic and upper lumbar segments (T1-L2), provide neural input to excite sympathetic tissues and organs that provide homeostatic and metabolic support during movement and exercise. We hypothesized that ascending propriospinal neurons located in the lumbar spinal cord provide synaptic input to thoracic SPNs, providing a spinal neural mechanism explaining improved motor and autonomic function in response to spinal cord stimulation. Here, we demonstrate that synaptic contacts from locomotor-related V3 interneurons (INs) are present in all thoracic laminae. Injection of an anterograde tracer into lumbar segments demonstrated that 8-20% of glutamatergic input onto SPNs originated from lumbar V3 INs and displayed a somatotopographical organization of synaptic input to thoracic SPNs, with rostral lumbar V3 INs projecting to rostral thoracic, and caudal lumbar V3 INs projecting to caudal thoracic SPNs. Whole cell patch clamp recording in SPNs demonstrated prolonged depolarizations or action potentials in response to optical activation of either lumbar V3 INs in spinal cord preparations or in response to optical activation of V3 terminals in thoracic slice preparations. This work demonstrates a direct intraspinal connection between lumbar locomotor and thoracic sympathetic networks and suggests communication between motor and autonomic systems may be a general function of the spinal cord. Key pointsO_LIWe provide direct anatomical and electrophysiological evidence of an ascending intraspinal synaptic connection between lumbar motor and thoracic sympathetic autonomic neural systems. C_LIO_LIThese connections are formed between lumbar locomotor related V3 interneurons and thoracic sympathetic preganglionic neurons (SPNs) C_LIO_LIV3 synaptic input accounts for [~] 20% of glutamatergic input to SPNs. C_LIO_LIOptical activation of lumbar V3 interneurons elicit action potentials in thoracic SPNs. C_LIO_LIThis intraspinal pathway may explain why electrical stimulation of the lumbar region in persons with long-standing motor complete spinal cord injury improves both motor and sympathetic function. C_LIO_LIThese findings suggest communication between motor and autonomic systems may be a general feature of spinal cord function and await further research to explore this concept. C_LI

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Chacon, C., Nwachukwu, C. V., Shahsavani, N., Cowley, K. C., Chopek, J. W.. 2023-04-07. Lumbar locomotor-related V3 interneurons provide direct excitatory synaptic input onto thoracic sympathetic preganglionic neurons. https://doi.org/10.1101/2023.04.06.535901

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