Distinct neural substrates for flexible and automatic motor sequence execution

Abstract

The ability to flexibly sequence movements into longer actions enables our rich behavioral repertoire. However, this feat can be cognitively demanding, leading to slow and error-prone performances. To achieve fast and fluid performance, the same motor sequence is practiced extensively until it is automatic. The neural circuits underlying automatic motor execution are thought to differ from those for executing flexible ones, but this distinction is not well understood. To address this, we trained rats to perform sequences of three lever presses in both flexible sessions – where cues instructed the sequence order – and in automatic ones – where a single uncued sequence was repeated. We found that neural activity in sensorimotor striatum primarily encodes low-level movement kinematics, regardless of the execution mode or sequence, whereas motor cortex activity reflects more high-level sequence information. Consequently, lesions to sensorimotor striatum affect the movement kinematics across both flexible and automatic movement sequences. This disrupted high-level sequence structure for only the automatic, but not visually-guided flexible behavior, which were rescued by the external cues, mirroring results from Parkinsonian patients. Lesions to motor cortex disrupted flexible sequence execution, indicating its vital role in high-level sequencing of motor elements. Interestingly, motor cortex lesions also affected automatic sequences when animals trained on both automatic and flexible modes execution modes, but for animals trained only on the automatic task, performance was largely spared, suggesting flexible performance interferes with subcortical consolidation of automatic sequences. This work provides important insights into the hierarchical and distributed control of flexible and automatic motor sequences and characterizes the circumstances under which the motor cortex is essential for sequence execution.