Plasticity of spinal rhythm generating interneurons after injury and training
Funded in: 2015, 2016, 2017, 2018
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Problem: The spinal locomotor network might be a prominent therapeutic target after SCI, but is not fully understood.
Target: Evaluate the consequences of injury and subsequent exercise training on rhythm generating neurons.
Goal: It might lead to discovery of targets for boosting spinal locomotor excitability, allowing for more refined therapeutic strategies.
Although the spinal locomotor network is not fully understood, it has been a prominent therapeutic target following spinal cord injury (SCI). Importantly, most injuries occur above the level of the spinal locomotor circuitry. Therefore, it is accessible for improving motor control and function.
Impressive outcomes in both SCI patients and animal models have been shown using stimulation and/or exercise training strategies designed to target this system. Spinal rhythm generating neurons receive a steady input from the brain and convert it into a rhythmic signal. In injured patients, these spinal neurons are still present; however, the inputs they receive from the brain are severely reduced. Therefore, these neurons and their communications to downstream neurons are an obvious entry point for studying SCI and treatment effects.
Little is known about the connectivity of rhythm generating neurons and there is no data showing the effects of SCI and training on these neurons or their connections. This project will utilize a mouse model of SCI to evaluate the consequences of injury and subsequent exercise training on rhythm generating neurons and their connections to downstream targets. This will be accomplished using a combination of electrophysiological and optogenetic techniques.
The results will provide targets for boosting spinal locomotor excitability and will reveal mechanisms for the beneficial effects of exercise training, a treatment currently used in humans, allowing for more refined therapeutic strategies.