Spinal Cord Injury: The Lamprey Model

Following severe spinal cord injury (SCI), brain locomotor command systems are disconnected from spinal motor networks, resulting in paralysis caudal to the lesion. In higher vertebrates, such as birds and mammals, the CNS is a restrictive environment for axonal regeneration. As a result, axons of descending brain neurons, including reticulospinal (RS) neurons, are unable to grow through a spinal injury site, and there is virtually no behavioral recovery. In contrast, the CNS of lampreys and certain other lower vertebrates is permissive for axonal growth. Thus, following SCI, descending brain neurons regenerate their axons and reconnect with spinal targets caudal to a healed spinal lesion site, resulting in recovery of locomotion and other behavioral functions in a few weeks. The lamprey has a number of very powerful advantages that make it ideally suited for investigating the mechanisms that support axonal regeneration and result in behavioral recovery. The present review will focus on the benefits and unique findings from SCI studies using the lamprey, particularly with regard to recovery of locomotor behavior. Potentially, the lamprey can provide a set of cellular conditions that are required for substantial axonal regeneration and recovery of behavioral functions. These conditions, if created in mammals following SCI, presumably would support axonal regeneration and result in behavioral recovery. Finally, even though the lamprey CNS is permissive for axonal outgrowth following SCI, neural regeneration has some limitations in this animal that reveal potential problems which might occur in the future if the mammalian CNS can be modified to be substantially permissive for axonal regeneration, perhaps closer to that in the lamprey. A better understanding of the mechanisms that support, as well as limit, axonal regeneration in the lamprey could provide insights into methods for improving recovery of function in spinal cord-injured higher vertebrates, including perhaps humans.