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bioRxiv · 10.1101/2025.10.14.681171

Ascending propriospinal modulation of thoracic sympathetic preganglionic neurons during lumbar locomotor activity

Dominguez-Rodriquez, L. E.·Nwachukwu, C. V.·Shahsavani, N.·Garcia, J.·Chopek, J. W.·Cowley, K. C.
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Abstract

Although the autonomic sympathetic system is activated in parallel with locomotion, the underlying neural mechanisms mediating this coordination are not completely understood. Descending exercise or central command signals from hypothalamic and brainstem regions are thought to activate thoracic spinal sympathetic neurons in parallel with descending locomotor commands. In turn, subsets of thoracic sympathetic preganglionic neurons (SPNs) then increase activation of a constellation of tissues and organs that provide homeostatic and metabolic support during movement and exercise. It is known that neurons within the spinal cord (propriospinal networks) can generate well-coordinated and sustained locomotor activity but whether these propriospinal networks contribute to coordination between locomotor and autonomic systems is unknown. To investigate this, we applied neurochemicals to elicit whole-cord or lumbar-evoked locomotor activity in an in vitro spinal cord preparation, simultaneously recording lumbar ventral root (VR) activity and changes in calcium fluorescence of pre-labelled SPNs in thoracic segments. Using whole-bath drug application to elicit hindlimb locomotor activity, recorded SPN responses were increased in rostral (T4 - T7) compared to caudal (T8 - T11) segments. When locomotor-inducing neurochemicals were applied only to the lumbar region using a split-bath configuration, SPN population responses were increased in rostral (T4-7) but not caudal (T8-9) segments during both tonic and rhythmic VR activity. In both approaches, the greatest numbers of SPNs with increased fluorescence during rhythmic activity were in T6/7, whereas the greatest numbers with unchanged or decreased fluorescence were in caudal segments (T8-T11). Together these findings reveal a strong ascending lumbar to thoracic integrating communication pathway and may represent a key feature of spinal neural network function normally. Such communication pathways should be further investigated for targeted autonomic function(s) activation and therapeutic benefit after spinal cord injury.

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Dominguez-Rodriquez, L. E., Nwachukwu, C. V., Shahsavani, N., Garcia, J., Chopek, J. W., Cowley, K. C.. 2025-10-15. Ascending propriospinal modulation of thoracic sympathetic preganglionic neurons during lumbar locomotor activity. https://doi.org/10.1101/2025.10.14.681171

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