Contribution of the Peripheral Nervous System to Instrumental Learning and Performance

Previous research 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, which reduces net shock exposure (Grau et al., 1998). Prior studies have examined the mechanisms that mediate this learning, but little is known about how or where the consequences of learning are stored (memory). The goal of this dissertation proposal is to examine the neural modification(s) that preserve learned behavioral effects over time. It is clear that the central nervous system plays an essential role in instrumental learning. During the acquisition of instrumental learning, the connections between the peripheral nervous system (PNS) and the central nervous system must remain intact (Crown et al., 2002a). Acquisition is also disrupted by intrathecal application of pharmacological agents (lidocaine) that inhibit spinal reflexes (Crown et al., 2002a). The experiments outlined in this dissertation are motivated by an unexpected observation: while application of lidocaine to the spinal cord prior to training blocks acquisition of the instrumental response, inactivating spinal neurons has no effect on the maintenance of the instrumental response. These data suggest that, after the instrumental response is acquired, a peripheral component is capable of maintaining the instrumental response. Aim 1 examined how inhibiting the spinal cord influenced the maintenance of instrumental learning. Intrathecal lidocaine inhibited a spinal withdrawal reflex and instrumental learning, but did not affect the maintenance of the learned response. Expanding on these results, Aim 2 examined how disconnecting the PNS from the spinal cord would influence the maintenance of instrumental learning. If a PNS to spinal cord connection is needed for the maintenance of instrumental learning, then removing that connection by a sciatic transection should disrupt performance of the instrumental response. Together, the results of Aims 1 & 2 confirm that a peripheral alteration contributions to the maintenance of instrumental behavior.
In Aim 3, I developed a procedure that would allow for drug delivery directly to the tibialis anterior muscle. If the neuromuscular junction is capable of influencing a spinal reflex, then blocking the neuromuscular junction with an antagonist (curare) should disrupt the acquisition and maintenance of the instrumental response. Based on the results of Aim 3, Aim 4 investigated how other pharmacological manipulations at the neuromuscular junction can influence the acquisition and maintenance of the instrumental response. Using glutamate receptor antagonists (CNQX and MK-801), I showed that glutamatergic signaling plays an essential role.