Spinal cord maturation and locomotion in mice with an isolated cortex

Area of Science:

• Neuroscience
• Developmental Biology
• Motor Control

Background:

• The spinal cord is crucial for motor behavior, integrating sensory information and motor output from supraspinal centers.
• Corticofugal pathways, including the corticospinal tract (CST), control spinal motor output, but the impact of their congenital absence on spinal cord development and function is not well understood.
• Spinal cord plasticity is recognized in adult models for functional recovery, but developmental dependence on cortical input requires further investigation.

Purpose of the Study:

• To investigate the role of corticofugal connections in the maturation of the spinal motor network.
• To determine the extent of spinal cord function preservation in the congenital absence of corticospinal and thalamocortical tracts.

Main Methods:

• Utilized Celsr3/Foxg1 mutant mice with genetically ablated cortico-subcortical connections during early development.
• Assessed motor behaviors through open-field tests, including locomotion, climbing, and swimming.
• Conducted histological analyses of spinal motor neurons and interneurons, alongside electromyography to evaluate motor output.

Main Results:

• Celsr3/Foxg1 mice exhibited hyperactivity in open-field tests but retained basic motor abilities like walking and swimming.
• Mutant animals showed a reduced number of spinal motor neurons with atrophic dendritic trees and decreased motor axon terminals.
• Specific interneuron populations (cholinergic, calbindin, calretinin) were increased, while others (reelin, parvalbumin) remained unchanged.

Conclusions:

• Provides the first genetic evidence that the spinal motor network requires corticofugal connections for full maturation.
• Demonstrates that significant motor function can be preserved despite the congenital absence of the corticospinal tract (CST).
• Highlights the complex interplay between descending pathways and spinal cord development in establishing motor control.