Spinal cord injury: how neurons could reconnect

Spinal cord injuries can cause lesions to the nerves of the motor circuit, causing devastating effects on limb movement. However, in cases of incomplete spinal cord injury, patients can regain partial basic motor ability under certain conditions. The theory is that the uninjured part of the spinal cord tissue helps to form new neuronal circuits that bypass the injured site. However, how this re-routing occurs was unclear until now.

The lab of Gregoire Courtine at the EPFL Brain Mind Institute and Silvia Arber’s group at the FMI and the University of Basel, have shown in a mouse model that the re-organizing of the neuronal motor circuit is triggered and promoted through a sensory feedback channel connecting to sensors inside skeletal muscles called “muscle spindles”. Embedded in muscle tissue, muscle spindles stretch or contract along with muscle movement (e.g. in the arms and legs), gathering direct information about the position of the body, which is then transmitted to the spinal cord through sensory neurons that connect to the muscle spindles. This feedback circuit allows us to know where every part of our body is positioned, even with our eyes closed.

Using high-resolution motion analysis and neuron-tracing techniques, the researchers found that limb movement in mice activates this sensory feedback loop. This, in turn, promotes repairing and reorganization in the damaged spinal network after injury and resulting in the restoration of basic motor functions. "The sensory feedback loops from muscle spindles are therefore a key factor in the recovery process," says Silvia Arber.

The work shows that muscle spindles are critical in reversing the devastating impact of spinal cord injury. Consequently, it suggests that activation of muscle spindles is essential to promote the recovery process of damaged neuronal networks following spinal cord injury. This means that therapeutic approaches with the most potential for success should aim to use the muscles extensively, since the more intensely muscles are used, the higher the stimulation of muscle spindle feedback circuits. This therapeutic approach is the focus of Gregoire Courtine’s lab, specifically targeting these feedback pathways to improve recovery following spinal cord injury.

This work represents a collaboration between EPFL’s Brain Mind Institute and Silvia Arber’s group at the Friedrich Miescher Institute Centre for Biomedical Research and the University of Basel Biozentrum.

Publication
Takeoka A, Vollenweider I, Courtine G, Arber S. Muscle Spindle Feedback Directs Locomotor Recovery and Circuit Reorganization after Spinal Cord Injury. Cell 159(7):1626-1639. 18 December 2014. DOI: http://dx.doi.org/10.1016/j.cell.2014.11.019