title: Functional changes in deep dorsal horn interneurons following spinal cord injury are enhanced with different durations of exercise training.
abstract: Exercise training after spinal cord injury (SCI) enhances collateral sprouting from axons near the injury and is thought to promote intraspinal circuit reorganisation that effectively bridges the SCI. The effects of exercise training, and its duration, on interneurons in these de novo intraspinal circuits are poorly understood. In an adult mouse hemisection model of SCI, we used whole-cell patch-clamp electrophysiology to examine changes in the intrinsic and synaptic properties of deep dorsal horn interneurons in the vicinity of a SCI in response to the injury, and after 3 and 6 weeks of treadmill exercise training. SCI alone exerted powerful effects on the intrinsic and synaptic properties of interneurons near the lesion. Importantly, synaptic activity, both local and descending, was preferentially enhanced by exercise training, suggesting that exercise promotes synaptic plasticity in spinal cord interneurons that are ideally placed to form new intraspinal circuits after SCI. Following incomplete spinal cord injury (SCI), collaterals sprout from intact and injured axons in the vicinity of the lesion. These sprouts are thought to form new synaptic contacts that effectively bypass the lesion epicentre and contribute to improved functional recovery. Such anatomical changes are known to be enhanced by exercise training; however, the mechanisms underlying exercise-mediated plasticity are poorly understood. Specifically, we do not know how SCI alone or SCI combined with exercise alters the intrinsic and synaptic properties of interneurons in the vicinity of a SCI. Here we use a hemisection model of incomplete SCI in adult mice and whole-cell patch-clamp recording in a horizontal spinal cord slice preparation to examine the functional properties of deep dorsal horn (DDH) interneurons located in the vicinity of a SCI following 3 or 6 weeks of treadmill exercise training. We examined the functional properties of local and descending excitatory synaptic connections by recording spontaneous excitatory postsynaptic currents (sEPSCs) and responses to dorsal column stimulation, respectively. We find that SCI in untrained animals exerts powerful effects on intrinsic, and especially, synaptic properties of DDH interneurons. Plasticity in intrinsic properties was most prominent at 3 weeks post SCI, whereas synaptic plasticity was greatest at 6 weeks post injury. Exercise training did not markedly affect intrinsic membrane properties; however, local and descending excitatory synaptic drive were enhanced by 3 and 6 weeks of training. These results suggest exercise promotes synaptic plasticity in spinal cord interneurons that are ideally placed to form new intraspinal circuits after SCI.
authors.affiliation: School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan 2308, NSW, Australia.
authors.forename: M M
authors.initials: MM
authors.lastname: Rank
authors.forename: J R
authors.initials: JR
authors.lastname: Flynn
authors.forename: C R
authors.initials: CR
authors.lastname: Battistuzzo
authors.forename: M P
authors.initials: MP
authors.lastname: Galea
authors.forename: R
authors.initials: R
authors.lastname: Callister
authors.forename: R J
authors.initials: RJ
authors.lastname: Callister
mesh_terms: D000818:Animals; D007395:Interneurons / Q000502:physiology*; D008297:Male; D008810:Mice, Inbred C57BL; D010805:Physical Conditioning, Animal / Q000502:physiology*; D066148:Spinal Cord Dorsal Horn / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000503:physiopathology*