Anatomical Diversity of the Adult Corticospinal Tract Revealed by Single-Cell Transcriptional Profiling

The Journal of Neuroscience, 2023 · DOI: https://doi.org/10.1523/JNEUROSCI.0811-22.2023 · Published: November 22, 2023

Simple Explanation

The corticospinal tract (CST) is a key motor pathway, and damage to it can cause lasting functional impairments. Current repair strategies are not optimal due to a limited understanding of the molecular differences within the adult CST. This study combines retrograde tracing with single-cell RNA sequencing to identify different types of corticospinal neurons (CSNs) that connect to forelimbs and hindlimbs. The research uses machine learning to differentiate CSNs from other cortical neurons, which could help in studying CST development, targeting repair strategies, and screening for growth activators after spinal cord injury.

Study Duration

Not specified

Participants

Adult male and female mice

Evidence Level

Not specified

Key Findings

1
CSNs segregate along the forelimb and hindlimb axis and by supraspinal axon collateralization.
2
Intact adult CSNs express genes previously thought to be unique to nonspinally terminating projection neurons.
3
Forelimb and hindlimb CSNs differentially innervate supraspinal structures, indicating that CSNs influence motor output beyond spinal motor circuitry.

Research Summary

This study combines retrograde tracing and scRNAseq to identify and characterize CSN subtypes based on their spinal and supraspinal projections. Machine learning tools were used to classify CSNs and limb-specific CSNs, revealing that CSNs are more similar to nonspinal L5 neurons than layer 2/3 neurons. The research demonstrates that FL and HL CSNs differ in their supraspinal innervation patterns and gene expression, providing insights for targeted repair strategies after spinal cord injury.

Practical Implications

Targeted Repair Strategies

The identification of unique molecular characteristics of CSN subtypes can inform more precise therapeutic interventions for spinal cord injury.

Drug Screening

The CSN gene lists can be leveraged for in vitro and in vivo screening to identify factors that promote axon growth and survival in specific CSN subtypes.

Understanding Motor Control

The discovery of supraspinal connectivity of CSNs provides new insights into how the CST influences motor processing beyond spinal motor circuitry.

Study Limitations

1
Potential undersampling of CSNs from the rostral forelimb area (RFA).
2
The identified spinal enlargement level transcriptional resolution resolves broad FL and HL-level functional differences; however, there could also be within and between spinal segment specificity.
3
Study limited to adult mice.

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