Learning Within the Spinal Cord: Clinical Implications

描述（由申请人提供）：传统上，脊髓一直是

DESCRIPTION (provided by applicant): Traditionally, the spinal cord has been viewed as a conduit between the brain and the periphery, organizing some simple reflexes but otherwise contributing little to learning and behavior. However, recent studies suggest that a great deal of information processing occurs within the spinal cord, and that this system not only tunes the afferent and efferent input/output at the brain's bidding but also adapts on its own to new environmental relations. Learning within the spinai cord can be studied using rats that have had the spinal cord cut at the second thoracic vertebra. A response-outcome contingency is established by applying shock to one hindleg whenever the leg falls below a preset criterion. Spinal neurons appear sensitive to this instrumental contingency, for subjects quickly learn to maintain their leg in a flexed position, effectively minimizing exposure to shock. This instrumental learning is facilitated by prior exposure to contingent shock and disrupted by noncontingent shock. It appears contingent training enables behavioral potential while noxious noncontingent stimuli undermine behavioral potential. The proposed experiments focus on the mechanisms that foster and preserve behavioral plasticity within the spinal cord and the implications of this work for the recovery of function after spinal cord injury. Studies proposed will examine the retention of the facilitory effect, the impact of Pavlovian contingencies, and whether clinically relevant stimuli (nerve injury, inflammation) affect behavioral potential. It is suggested that some neurochemical systems (noradrenergic, and/or serotonergic) may help preserve behavioral potential. Experiments will examine whether engaging these systems protects the spinal cord from the deleterious effects of noncontingent noxious stimuli. Finally, studies will explore the underlying mechanisms using immunocytochemical techniques (c-fos) and whether the experimental manipulations affect the recovery of locomotor behavior after a contusion injury. It is hoped that discovering the mechanisms that promote and protect behavioral plasticity within the spinal cord will lead to new behavioral and pharmacological treatments that foster recovery of function after spinal cord injury.