Motor-Skill Learning in a Novel Running-Wheel Paradigm: Long-Term Memory Consolidated by D1 Receptors in the Striatum

Abstract

The sensorimotor striatum mediates procedural learning. Our previous studies revealed molecular changes in the sensorimotor striatum associated with motor-skill learning in a running-wheel task. In the present series of studies, we developed a novel test to measure the motor skill learned during running-wheel training and investigated mechanisms of wheel-skill learning in the striatum. Our results show that even a short wheel training (two daily sessions) produces robust long-term memory that lasts for months. Studies using systemic and intrastriatal D1 dopamine receptor antagonism in conjunction with cocaine treatment indicate that the acquisition of this wheel skill is dependent on optimal D1 receptor signaling in the striatum. Moreover, these studies demonstrate that striatal D1 receptors are critical for the formation of late, but not early, long-term skill memory. Further studies show that striatal processing after the training mediates consolidation of this long-term skill memory, as this memory formation was disrupted by posttrial drug infusions into the striatum. Interestingly, pretrial administration of cocaine prevented this posttrial interference, suggesting that cocaine stabilizes processes of memory formation, possibly by enhancing learning-related molecular changes. Together, these findings demonstrate that this running-wheel paradigm is an efficient model to investigate mechanisms of procedural learning and memory formation.