Abstract
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-HTR2α 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.
Highlights
Serotonin (5-HT) is a monoamine neurotransmitter synthesized by a subclass of neurons termed serotonergic neurons that are present in the brainstem
To analyze the integration of those 5-HT boutons and determine whether this increased serotonergic innervation of the spinal cord results in excessive contacts onto the neurons that execute motor behaviour i.e. motoneurons, we focused on two additional analysis in the ventral horn
In contrast to 5-HT fibers, 5-HT2R2α expression is similar in control and Sema7A deficient animals (Fig. 1f) again supporting the concept that homeostatic regulation preserves similar levels of serotonergic transmission despite a marked increase in serotonergic innervation
Summary
Serotonin (5-HT) is a monoamine neurotransmitter synthesized by a subclass of neurons termed serotonergic neurons that are present in the brainstem. Sema7A signaling was recently reported to induce activity-dependent olfactory synapse formation during the neonatal period [19] In addition to these well-established roles in promoting axon outgrowth and in regulating synapse formation and elimination, Sema7A was recently shown to control the precise targeting of monoaminergic axons, in particular, the segregation of nigrostriatal and mesolimbic dopaminergic pathways [20]. Because Sema7A is expressed in the developing spinal cord [21], but is present in adulthood all through the different laminae of the spinal cord [22], we hypothesized that Sema7A signaling could be an important molecular cue that instructs the patterning of monoaminergic inputs to spinal locomotor networks
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
