Brett Hilton, German Centre for Neurodegenerative Diseases (DZNE), Bonn, Germany

Dissecting the Role of Neuronal Activity in CNS Axon Regeneration and Functional Recovery following Spinal Cord Injury

Funded in: 2017, 2018, 2019


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Problem: Axons fail to regenerate after SCI

Target: Stimulating and/or inhibiting electrical activity to promote axon growth

Goal: New insights in the mechanisms of axon growth to develop clinically relevant strategies for regeneration

 

After spinal cord injury, the processes of nerve cells (axons) fail to regenerate, disrupting communication between the brain and the rest of the body. Why axons fail to regenerate is still not well understood.

A basic property of nerve cells is that they are electrically excitable. This property is the basis of virtually every function of the brain and spinal cord. Despite its fundamental importance, how electrical activity influences the capacity of nerve cells to regenerate following spinal cord injury is unclear. Some research indicates that stimulating electrical activity promotes axon growth whereas other research indicates that electrical silencing serves as an injury signal that allows growth to start.

New technologies, termed optogenetics and chemogenetics, allow precise control of nerve cell activity using laser light or drugs. In this project, we will combine optogenetics and chemogenetics with live imaging of axons to determine how electrical activity influences regeneration after spinal cord injury. Doing so, we will determine the role of electrical activity at both acute and chronic stages of injury, and also assess whether the role of activity changes over time.

After determining the most effective way to promote regeneration, we will assess whether manipulating nerve cell electrical activity promotes hand recovery in a mouse model of cervical (neck region) spinal cord injury.

This work will inform clinically relevant strategies of regulating nerve cell activity to influence regeneration and recovery following spinal cord injury. In addition, clinical trials have begun using optogenetics to treat certain eye disorders, and it may be possible to develop similar treatments for spinal cord injury.