Tuesday, April 1, 2025
4/1/2025
Motor Skill and the Cortical Motor Areas - PROJECT SUMMARY The acquisition and retention of skilled sequential movements is a fundamental part of human behavior. We still know little about where and when plastic changes occur in the cortical motor areas to learn and maintain skilled sequential movements. Here, we propose to study the temporal evolution of the learning and maintenance of skilled sequential movements in primary motor cortex (M1) and dorsal premotor cortex (PMd) by pharmacologically manipulating information storage in these areas. We will train monkeys to perform two tasks. In one task, the monkeys perform sequential reaching movements guided by memory. Skill on the memory-guided sequential movements task is acquired through considerable practice. For a control task, the monkeys perform reaching movements guided by visual cues. Our preliminary data showed that an injection of an inhibitor for protein synthesis or an inhibitor for DNA methylation into M1 of monkeys disrupted the performance of acquired sequential movements without affecting the performance of visually guided reaching. We will apply these approaches to examine the nature and time course of plasticity processes in M1 and PMd that support the learning and maintenance of extensively practiced motor skills. First, to determine whether the neural trace for sequential movements is gradually consolidated in M1 with extended practice, we will inject an inhibitor of protein synthesis into M1 at multiple time points during learning of sequential movements. We hypothesize that the motor skill is repetitively consolidated through protein synthesis every time a subject practice, and that the rate of consolidation declines as learning proceeds. Second, to determine when PMd is involved in learning the associations between movement elements in a sequence, we will inject an inhibitor of protein synthesis into PMd at multiple time points during learning of sequential movements. We hypothesize that learning processes in M1 and PMd operate in different time frames. Third, to determine whether M1 and PMd become sites of long-term storage for the acquired sequential movements and remain critical for the maintenance of the acquired sequential movements, we will inject an inhibitor of DNA methylation into these areas. We postulate that the injection will disrupt the maintenance of memory-guided sequential movements after long term practice and that the monkey will need to relearn the sequence to recover his performance after the injection. Completion of the proposed studies will expand our understanding of the temporal evolution of the learning, as animals slowly become highly skilled with ongoing long-term practice and consolidation. That level of motor sequence expertise is never studied in rodents and rarely in monkeys, yet it is a common feature of everyday human motor performance. The results will provide information to develop new strategies for acquiring motor skills and enhance functional recovery following stroke or traumatic brain injury.
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