Cholinergic mechanisms in spinal locomotion—potential target for rehabilitation approaches

Frontiers in Neural Circuits, 2014 · DOI: 10.3389/fncir.2014.00132 · Published: November 6, 2014

Spinal Cord Injury Neurology Rehabilitation

Simple Explanation

This study investigates the role of cholinergic systems in controlling locomotion, both in normal conditions and after spinal cord injury. It explores the potential of the spinal cholinergic system as a target for rehabilitation approaches. The research examines the involvement of brainstem and spinal cholinergic systems in initiating and coordinating movement. It also looks at how the spinal cholinergic system might contribute to recovery after spinal cord injury. The study uses a combination of in vitro experiments on neonatal rat spinal cords, experiments on decerebrate cats, and experiments on spinalized cats and rats to investigate the effects of cholinergic agonists and antagonists on locomotion.

Study Duration

Not specified

Participants

Neonatal rats, decerebrate cats, spinal cats, chronic spinal rats

Evidence Level

Not specified

Key Findings

1
Enhancing the propriospinal cholinergic system in neonatal rats can produce well-coordinated locomotor activity in vitro.
2
In adult decerebrate cats, cholinergic systems do not appear to be required for the initiation or coordination of locomotion.
3
After spinal cord injury, a hyper-cholinergic state may develop that interferes with locomotion, and cholinergic antagonists can improve locomotor activity.

Research Summary

The study found that enhancing the effects of the endogenous cholinergic propriospinal system in neonatal rats can lead to well-coordinated locomotion in vitro, mediated by M2 and M3 muscarinic receptors. Experiments in adult decerebrate cats showed that blocking cholinergic neurotransmission, either muscarinic or nicotinic, did not abolish MLR-evoked treadmill locomotion, suggesting that cholinergic systems are not essential for locomotion in adult mammals. Contrary to expectations, the study found that cholinergic antagonists could facilitate locomotion after spinal cord injury in both cats and rats, suggesting the development of a hyper-cholinergic state that suppresses locomotor activity. This effect seems to involve the control of afferent input to the spinal cord.

Practical Implications

Rehabilitation Strategies

Cholinergic antagonists may be a potential therapeutic strategy for improving locomotor recovery after spinal cord injury by counteracting a hyper-cholinergic state.

Targeted Therapies

Future research should focus on identifying and targeting specific cholinergic neurons and receptors involved in the suppression of locomotion after SCI.

Understanding Plasticity

Further investigation is needed to understand the mechanisms underlying the development of the hyper-cholinergic state after SCI and the role of afferent input control.

Study Limitations

1
The precise mechanisms by which cholinergic systems influence locomotor networks after SCI are not fully understood.
2
The study focuses on animal models, and further research is needed to determine the applicability of these findings to human SCI.
3
The specific contributions of different types of cholinergic neurons to the observed effects require further investigation.

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