Abstract: BACKGROUND: The recovery of function after spinal cord injury depends on the functional remodeling of the motor cortex. However, the anatomical evidence underlying the functional remodeling of the motor cortex is still illusive. Analyzing the anatomical changes in the motor cortex after spinal cord injury can provide new ideas and research directions for regulating functional recovery and rehabilitation after spinal cord injury.
OBJECTIVE: To analyze the neural circuit structural basis of functional remodeling of the primary motor cortex after spinal cord injury.
METHODS: C57BL/6J mice were randomly divided into a sham operation group and a spinal cord injury group. The adeno-associated virus vectors expressing the fusion protein of Cre recombinase were injected into C4 of mice of both groups. The adeno-associated virus vectors with Cre recombinase-inducible expression of avian sarcoma/leukosis envelope glycoprotein receptor TVA and rabies glycoprotein were injected into the primary motor cortex. Fourteen days later, a C6 dorsal hemisection mice model was established in the spinal cord injury group. The pseudotyped rabies virus was injected into the primary motor cortex of mice of both groups. After 7 days, brain samples were collected and frozen sections were made. The distribution of input neurons innervating corticospinal motor neurons in the brain was observed and analyzed quantitatively. 
RESULTS AND CONCLUSION: Fluorescence microscopy observation and quantitative analysis found that input neurons innervating corticospinal motor neurons of the primary motor cortex in mice of both groups were distributed in the cerebral cortex, thalamus and midbrain. Among them, in the sham operation group, the number of input neurons in the mouse cerebral cortex accounted for (84.0±3.6)% of total brain input neurons; that in the thalamus accounted for (10.6±2.3)%, and that in the midbrain accounted for (0.7±0.4)%. Direct synaptic input neurons in the spinal cord injury group accounted for (81.7±1.0)%, (13.1±0.5)%, and (1.6±0.8)% in the cerebral cortex, thalamus and midbrain, respectively. The proportion and number of primary motor cortex input neurons in the three regions of the spinal cord injury group did not differ significantly from that of the sham operation group. After spinal cord injury, the number of input neurons innervating corticospinal pyramidal motor neurons in various brain regions did not change significantly, suggesting that functional remodeling of the motor cortex after spinal cord injury may not only depend on changes in synaptic input related to injured corticospinal motor neurons, but also on transcriptional regulation changes within the injured neurons themselves.

Key words: spinal cord injury, corticospinal tract, primary motor cortex, whole brain inputs, pseudorabies rabies virus