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

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.

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Combining task-based rehabilitative training with PTEN inhibition promotes axon regeneration and upper extremity skilled motor function recovery after cervical spinal cord injury in adult mice

Behavioural Brain Research ◽

10.1016/j.bbr.2021.113197 ◽

2021 ◽

Vol 405 ◽

pp. 113197

Author(s):

Lu Pan ◽

Botao Tan ◽

Weiwei Tang ◽

Meiling Luo ◽

Yuan Liu ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Upper Extremity ◽

Motor Function ◽

Axon Regeneration ◽

Cervical Spinal Cord ◽

Adult Mice ◽

Function Recovery ◽

Cord Injury ◽

Pten Inhibition

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Brain-wide quantification of the supraspinal connectome

10.1101/2021.06.10.447885 ◽

2021 ◽

Author(s):

Zimei Wang ◽

Adam Romanski ◽

Vatsal Mehra ◽

Yunfang Wang ◽

Benjamin C. Campbell ◽

...

Keyword(s):

Spinal Cord ◽

Web Based ◽

Locomotor Recovery ◽

Adult Mice ◽

Comprehensive Information ◽

Normal Behavior ◽

Wide Range ◽

Cord Injury ◽

Functional Consequences ◽

Intuitive Manner

The supraspinal connectome is essential for normal behavior and homeostasis and consists of a wide range of sensory, motor, and autonomic projections from brain to spinal cord. Extensive work spanning a century has largely mapped the cell bodies of origin, yet their broad distribution and complex spatial relationships present significant challenges to the dissemination and application of this knowledge. Fields that study disruptions of supraspinal projections, for example spinal cord injury, have focused mostly on a handful of major populations that carry motor commands, with only limited consideration of dozens more that provide autonomic or crucial motor modulation. More comprehensive information is essential to understand the functional consequences of different injuries and to better evaluate the efficacy of treatments. Using viral retrograde labeling, 3D imaging, and registration to standard neuro-anatomical atlases we now provide a platform to profile the entire supraspinal connectome by rapidly visualizing and quantifying tens of thousands of supraspinal neurons, each assigned to more than 60 identified regions and nuclei throughout the brains of adult mice. We then use this tool to compare the lumbar versus cervically-projecting connectomes, to profile brain-wide the sensitivity of supraspinal populations to graded spinal injuries, and to correlate locomotor recovery with connectome measurements. To share these insights in an intuitive manner, we present an interactive web-based resource, which aims to spur progress by broadening understanding and analyses of essential but understudied supraspinal populations.

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