Changes in Spinal Neural Circuit Plasticity in a Rat Sciatic Nerve Transection Model.

Abstract

BACKGROUND AND AIM: Changes in neural plasticity crucially modulate functional recovery after central nerve injury. To describe morphological peripheral nerve injury-related changes, we comprehensively elucidated post-sciatic nerve transection (post-SNT) plasticity changes in the lumbar spinal corticospinal tract (CST), motor neurons, and cholinergic interneurons (CINs). METHODS: In a rat SNT model, we compared post-SNT changes in lumbar spinal cord plasticity at 2, 4, and 6 weeks with those in the Sham group. Using neural tracers and immunohistochemistry, we labeled and analyzed the CST axonal number and volume, motor neuron cell-body volume and synaptic inputs, and cholinergic interneuron (CIN) (medial and lateral, based on the distance from the central canal) number and synaptic inputs. RESULTS: Compared to the Sham group, the SNT groups showed no significant post-SNT changes in CST axonal number and volume. Motor neuron cell-body volume decreased by 29% at 6 weeks post-SNT, and vesicular glutamate transporter 1 (vGlut1) and vesicular acetylcholine transporter (vAchT) synaptic inputs decreased by 82-93% and 27-42%, respectively, from 2 weeks post-SNT onward. From 2 weeks post-SNT onward, cell numbers were maintained, although vGlut1 synaptic inputs increased by 98%-68% in lateral CINs. At 6 weeks post-SNT, a 44% reduction in cell numbers and a simultaneous 107% increase in vGlut1 synaptic inputs were noted in medial CINs. CONCLUSION: Following SNT, although CST axonal numbers remained unchanged, plasticity changes were observed in motor neurons and in CINs. CINs exhibited distinct plasticity changes depending on their localization.