Guillermo Garcia Alias, University of California Los Angeles, Los Angeles, USA

Promoting plasticity of reticulospinal axons to control forelimb reaching and grasping movements in rats depleted of corticospinal and rubrospinal tract axons

Funded in: 2011, 2012

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Of all the descending motor pathways, two tracts of axons, the corticospinal and rubrospinal tract, play a prominent role in controlling skilled movements, particularly of the more distal musculature of the forelimbs. If these tracts are damaged, reaching and grasping are severely impaired .

Damaged axons have a limited ability to regrow, sprout, and reinnervate target neurons in the spinal cord, creating chronic disconnection between supraspinal centres and the spinal cord. Pharmacological and rehabilitation therapies in animals have shown some potential in overcoming some of these limitations by promoting axonal plasticity which, in turn, can enhance the recovery of hand function. The present project will determine whether the recovery of skilled hand function after corticospinal and rubrospinal tract damage can be attributed to plastic changes in other spared descending spinal tracts.

We hypothesize that application of chondroitinase ABC (chABC) within the cervical spinal cord will remove inhibitory molecules and allow reticulospinal axonal sprouts to elongate and innervate the target interneurons of the corticospinal and rubrospinal tracts. In addition, task specific rehabilitation will reduce aberrant newly formed synaptic contacts in an activity-dependent manner and will promote the recovery of reaching and grasping.