AMPA-receptor mediated plasticity within the rat spinal cord

Previous research from our laboratory has demonstrated that the spinal cord is capable of a simple form of instrumental learning. In this instrumental learning paradigm, rats typically receive a complete spinal transection at the second thoracic vertebra, and are tested 24 hours after surgery. Subjects that receive shock to a hind leg quickly learn to maintain the leg in a flexed position, reducing net shock exposure whenever that leg is extended (controllable shock). Subjects that receive shock that is independent of leg position do not exhibit an increase in flexion duration (uncontrollable shock). This behavioral deficit can be induced with shock to the leg or tail and as little as 6 minutes of uncontrollable shock impairs learning for up to 48 hours. The present thesis explores how the related ?-amino-3-hydroxy-5-methyl-4- isoxazole propionic acid-receptor (AMPAR) ionotropic glutamate receptor affects spinal instrumental learning. Experiment 1 showed that inactivation of the AMPAR by administration of an antagonist blocks the acquisition of instrumental learning in a dose dependant fashion. Experiment 2 demonstrated that blocking the AMPAR after the acquisition of the instrumental response subsequently blocked the maintenance of that response. Experiment 3 revealed that antagonizing the AMPAR during uncontrollable shock blocked the acquisition of the learning deficit. Experiments 4-6 demonstrated that the activation of the AMPAR at high levels could acutely block the acquisition spinal instrumental learning. Understanding how the AMPAR influences learning in the spinal cord will lead us to develop therapeutic strategies for recovery of function after spinal cord injury.