Mesencephalic locomotor region stimulation—cuneiform or pedunculopontine?

Cell Reports Medicine, 2023 · DOI: https://doi.org/10.1016/j.xcrm.2023.100948 · Published: February 21, 2023

Spinal Cord Injury Neurology Rehabilitation

Simple Explanation

The mesencephalic locomotor region (MLR) is a midbrain structure that, when stimulated, can elicit stepping and even running. Researchers are exploring whether stimulating the MLR can help treat spinal cord injuries. There are differential roles for neuronal populations within the cuneiform (CnF) and pedunculopontine nuclei (PPN) within the MLR. CnF orchestrates fast-escape responses, whereas PPN acts mostly downstream of basal ganglia during slower exploratory behavior. Ablation of CnF had a more profound impact than deletion of PPN. Excitatory CnF, but not PNN, stimulation correlated with spontaneous improvement in locomotor score over time. It looks like CnF could mediate aspects of spontaneous recovery.

Study Duration

Not specified

Participants

Murine model of chronic spinal cord injury

Evidence Level

Not specified

Key Findings

1
Excitatory CnF, but not PNN, stimulation correlated with spontaneous improvement in locomotor score over time.
2
CnF stimulation modulates spatiotemporal muscle recruitment and improves coordination and walking speed overground.
3
CnF stimulation improved performance. Thus, mechanistically, these results suggest that the CnF is important for spontaneous locomotor recovery, and its stimulation can modulate muscle ﬁring to improve locomotion farther than occurs spontaneously in chronic spinal injured mice.

Research Summary

Roussel et al.1 provide new insight into mecencephalic locomotor region (MLR) stimulation to treat spinal cord injury in mice. Previously, it was unclear which part of the MLR to target. Now, evidence converges on cuneiform nucleus activation. Taken together, CnF stimulation modulates spatiotemporal muscle recruitment and improves coordination and walking speed overground. Thus, the convergence of these two studies provides evidence that CnF stimulation could prove an effective therapeutic target for improvement in lower limb function, espe- cially in the population of individuals re- cruited for the current clinical trial8 who have some intact motor function below the level of lesion.

Practical Implications

Therapeutic Target

Cuneiform nucleus (CnF) stimulation could be an effective therapeutic target for improving lower limb function in individuals with spinal cord injury.

Clinical Trial Relevance

Findings are relevant to ongoing clinical trials using MLR-DBS, particularly for patients with some intact motor function below the lesion.

Spontaneous Recovery Insights

CnF plays a key role in spontaneous locomotor recovery following spinal cord injury.

Study Limitations

1
Whether the reasonably extensive sparing in this particular lateral hemisection model could inﬂuence relative contribution of CnF and PNN could still be questioned.
2
Not specified
3
Not specified

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