Inhibition of protein synthesis in M1 of monkeys disrupts performance of sequential movements guided by memory

The production of action sequences is a fundamental aspect of motor skills. To examine whether primary motor cortex (M1) is involved in maintenance of sequential movements, we trained two monkeys (Cebus apella) to perform two sequential reaching tasks. In one task, sequential movements were instructed by visual cues, whereas in the other task, movements were generated from memory after extended practice. After the monkey became proficient with performing the tasks, we injected an inhibitor of protein synthesis, anisomycin, into M1 to disrupt information storage in this area. Injection of anisomycin in M1 had a marked effect on the performance of sequential movements that were guided by memory. In contrast, the anisomycin injection did not have a significant effect on the performance of movements guided by vision. These results suggest that M1 of non-human primates is involved in the maintenance of skilled sequential movements.


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The ability to perform a sequence of movements is a key component of motor skills, such as 18 typing and playing a musical instrument. How the brain binds elementary movements together 19 into meaningful actions has been a topic of much interest. The preparation for and generation 20 of sequential movements is classically thought to depend on the supplementary motor area 21 (SMA) and the pre-SMA (Roland et al., 1980;Tanji and Shima, 1994;Gerloff et al., 1997; 22 Shima and Tanji, 1998;Nakamura et al., 1998;Hikosaka et al., 2002;Picard and Strick, 2001; 23 Dayan and Cohen, 2011). According to this view, the primary motor cortex (M1) is thought to 24 produce the patterns of muscle activity that are necessary to implement the motor plans 1 generated by the premotor areas. There is growing evidence, however, that M1 of humans and 2 non-human primates is involved in the acquisition and retention of sequential movements. For 3 example, the activity of some M1 neurons appears to reflect the serial order of potential target 4 stimuli (Pellizzer et al., 1995;Carpenter et al., 1999). Similarly, a large number of M1 neurons 5 (~40%) and metabolic activity reflected aspects of learned movement sequences (Lu and Ashe,   Kleim et al., 2003). In these studies, local injection of an inhibitor for protein synthesis,

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We trained two monkeys (Cebus apella) on two tasks. In one task, the monkeys performed 4 sequential movements guided by memory (Repeating task) ( Fig. 1 a, b). As a control task, the 5 monkeys also were trained to perform reaching movements guided by visual cues (Random 6 task, for details see Methods). After the monkeys became proficient with performing the two 7 tasks (> 100 training sessions), we made injections of the protein synthesis inhibitor, 8 anisomycin, in M1. The injections of aniomycin solution (100 mg/ml) were placed at sites in 9 which intracortical stimulation evoked shoulder or elbow movements ( Fig. 1c-f, for details see 10 Methods). We analyzed the monkey's behavior before and after the injection separately for 11 each movement in each task. A movement from one target to the next is defined as a trial.

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The anisomycin injections had a significant effect on the performance of the movements during

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The incorrect responses during the Repeating task can be categorized as two types: errors of 21 accuracy and errors in direction. An accuracy error is a reach performed in the correct direction 22 (e.g., to the right in move 1-5), but to an endpoint outside of the correct target (e.g., short of 23 target 5). As shown in Fig. 2a, before the injection, the monkey made correct contact to target 24 5 on 96% of the trials in the Repeating task (sequence 5-3-1). After the anisomycin injection,

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In the present study, localized inhibition of protein synthesis in M1 resulted in a selective deficit 21 in the performance of internally generated sequential movements during the Repeating task.

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This observation emphasizes the importance of M1 for the generation of sequential movements 23 that are memory guided. Our results suggest that, although M1 is critical for movement 24 production, it also is involved in the maintenance of skilled sequential movements. the surgery (Fig 1d). When task performance returned to the pre-surgical level, we performed 20 a craniotomy to expose the cortex in the chamber.