Recovery from serious neurological injury requires substantial rewiring of neural circuits. Precisely-timed electrical stimulation could be used to restore corrective feedback mechanisms and promote adaptive plasticity after neurological insult, such as spinal cord injury (SCI) or stroke. This study provides the first evidence that closed-loop vagus nerve stimulation (CLV) based on the synaptic eligibility trace leads to dramatic recovery from the most common forms of SCI. The addition of CLV to rehabilitation promoted substantially more recovery of forelimb function compared to rehabilitation alone following chronic unilateral or bilateral cervical SCI in a rat model. Triggering stimulation on the most successful movements is critical to maximize recovery. CLV enhances recovery by strengthening synaptic connectivity from remaining motor networks to the grasping muscles in the forelimb. The benefits of CLV persist long after the end of stimulation because connectivity in critical neural circuits has been restored.

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Background Behavioral models relevant to stroke research seek to capture important aspects of motor skill typically impaired in human patients, such as coordination of distal musculature. Such models may focus on mice since many genetic tools are available for use only in that species, and since the training and behavioral demands of mice can differ from rats even for superficially similar behavioral readouts. However, current mouse tests are time consuming to train and score, especially in a manner producing continuous quantification. An automated assay of mouse forelimb function may provide advantages for quantification and speed, and may be useful for many applications including stroke research. New Method We present an automated assay of distal forelimb function. In this task, mice reach forward, grip and pull an isometric handle with a prescribed force. The apparatus partially automates the training process so that mice can be trained quickly and simultaneously. Results Using this apparatus, it is possible to measure long-lasting impairment in success rate, force pulled, latency to pull, and latency to success up to 22 weeks following photothrombotic cortical strokes in mice. Comparison with Existing Method(s) This assessment measures forelimb function as do pellet reach tasks, however it utilizes a different motion and provides automatic measures that can ease and augment the research process. Conclusions This high-throughput behavioral assay can detect long-lasting motor impairments, eliminates the need for subjective scoring, and produces a rich, continuous data set from which many aspects of the reach and grasp motion can be automatically extracted.

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