Semaphorin 7A restricts serotonergic innervation and ensures recovery after spinal cord injury

Descending serotonergic (5-HT) projections originating from the raphe nuclei form an important input to the spinal cord that control basic locomotion. The molecular signals that control this projection pattern are currently unknown. Here, we identify Semaphorin7A (Sema7A) as a critical cue that restricts serotonergic innervation in the spinal cord. Sema7A deficient mice show a marked increase in serotonergic fiber density in all layers of the spinal cord while the density of neurons expressing the corresponding 5-HTR2 alpha receptor remains unchanged. These alterations appear to be successfully compensated as no obvious changes in rhythmic locomotion and skilled stepping are observed in adult mice. When the system is challenged with a spinal lesion, serotonergic innervation patterns in both Sema7A-deficient and -competent mice evolve over time with excessive innervation becoming most pronounced in the dorsal horn of Sema7A-deficient mice. These altered serotonergic innervation patterns correlate with diminished functional recovery that predominantly affects rhythmic locomotion. Our findings identify Sema7A as a critical regulator of serotonergic circuit formation in the injured spinal cord.

Automated summary

In this study, the researchers identified Semaphorin7A (Sema7A) as a critical regulator of serotonergic circuit formation in the injured spinal cord, with Sema7A deficiency leading to an increase in serotonergic fiber density. While these alterations seem to be compensated in adult mice, spinal lesion challenge revealed changes in serotonergic innervation patterns, correlating with diminished functional recovery.