Brain-wide transcriptional profiling after spinal cord injury

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PROJECT SUMMARY The brain communicates with the spinal cord through a diverse set of neurons, collectively termed the supraspinal connectome. The supraspinal connectome carries a broad range of motor, sensory, and autonomic functions, and damage to descending tracts by spinal cord injury (SCI) thus results in a wide array of functional challenges: loss of fine motor control, loss of locomotion and balance, loss of sensation, neuropathic pain, bladder, bowel, temperature, and blood pressure dysregulation, loss of sexual function, and more. Addressing these myriad functional deficits will require a detailed understanding of the underlying cellular complexity. Here, using a mouse model, we will take advantage of advances in single sequencing technologies, combined with a barcoding strategy recently developed by our lab, to comprehensively profile the patterns of gene transcription that typify diverse classes of supraspinal neurons. We will then challenge descending neurons with spinal injury and monitor the resulting changes in gene expression population-by-population, yielding first-ever insight into commonalities and differences in the cellular damage response across the supraspinal connectome. Finally, we will treat diverse supraspinal cell types with Sox11, a transcription factor that has been shown to variably promote axonal repair or trigger cell death in different cell types, and profile its population-specific effects. Combined, this work will yield new insights into baseline molecular differences in supraspinal cell types, provide novel marker genes to simplify analysis of understudied cell types, and reveal populations that are innately sensitive to injury and/or attempted intervention.