RT Journal Article T1 Spontaneous regeneration of cholecystokinergic reticulospinal axons after a complete spinal cord injury in sea lampreys A1 González Llera, Laura A1 Santos Durán, Gabriel Nicolás A1 Sobrido Cameán, Daniel A1 Núñez-González, Carmen A1 Pérez-Fernández, Juan A1 Barreiro Iglesias, Antón K1 Spinal cord injury K1 Axonal regeneration K1 Cholecystokinin K1 Synaptic vesicles K1 Lampreys K1 Locomotor performance AB In contrast to humans, lampreys spontaneously recover their swimming capacity after a complete spinal cord injury (SCI). This recovery process involves the regeneration of descending axons. Spontaneous axon regeneration in lampreys has been mainly studied in giant descending neurons. However, the regeneration of neurochemically distinct descending neuronal populations with small-caliber axons, as those found in mammals, has been less studied. Cholecystokinin (CCK) is a regulatory neuropeptide found in the brain and spinal cord that modulates several processes such as satiety, or locomotion. CCK shows high evolutionary conservation and is present in all vertebrate species. Work in lampreys has shown that all CCKergic spinal cord axons originate in a single neuronal population located in the caudal rhombencephalon. Here, we investigate the spontaneous regeneration of CCKergic descending axons in larval lampreys following a complete SCI. Using anti-CCK-8 immunofluorescence, confocal microscopy and lightning adaptive deconvolution, we demonstrate the partial regeneration of CCKergic axons (81% of the number of axonal profiles seen in controls) 10 weeks after the injury. Our data also revealed a preference for regeneration of CCKergic axons in lateral spinal cord regions. Regenerated CCKergic axons exhibit colocalization with synaptic vesicle marker SV2, indicative of functional synaptic connections. We also extracted swimming dynamics in injured animals by using DeepLabCut. Interestingly, the degree of CCKergic reinnervation correlated with improved swimming performance in injured animals, suggesting a potential role in locomotor recovery. These findings open avenues for further exploration into the role of specific neuropeptidergic systems in post-SCI spinal locomotor networks. PB Elsevier SN 2001-0370 YR 2024 FD 2024 LK https://hdl.handle.net/10347/44567 UL https://hdl.handle.net/10347/44567 LA eng NO Computational and Structural Biotechnology Journal Volume 23, December 2024, Pages 347-357 NO Grant PID2020–115121 GB-I00 funded by MCIN/AEI/10.13039/501100011033 to A. Barreiro-Iglesias. Grant ED431C 2021/18 funded by Xunta de Galicia. Long-term EMBO fellowship ALTF 62–2021 to D.S.-C. by European Molecular Biology Organization. The Ramón y Cajal grant RYC2018–024053-I funded by MCIN/AEI/ 10.13039/501100011033 and by “ESF Investing in your Future” to J.P.-F. Xunta de Galicia (ED431B 2021/04 to J.P.-F. and ED481A 2022/433 to C.N.-G). DS Minerva RD 22 may 2026