Task-specific modulation of corticospinal neuron activity during motor learning in mice

Abstract

Motor skill learning relies on the plasticity of the primary motor cortex as task acquisition drives cortical motor network remodeling. Large-scale cortical remodeling of evoked motor outputs occurs during the learning of corticospinal-dependent prehension behavior, but not simple, non-dexterous tasks. Here we determine the response of corticospinal neurons to two distinct motor training paradigms and assess the role of corticospinal neurons in the execution of a task requiring precise modulation of forelimb movement and one that does not. In vivo calcium imaging in mice revealed temporal coding of corticospinal activity coincident with the development of precise prehension movements, but not more simplistic movement patterns. Transection of the corticospinal tract and optogenetic regulation of corticospinal activity show the necessity for patterned corticospinal network activity in the execution of precise movements but not simplistic ones. Our findings reveal a critical role for corticospinal network modulation in the learning and execution of precise motor movements.

Neuropathic pain in a chronic CNS injury model is mediated by CST-targeted spinal interneurons

“…Pyramidotomy was performed as previously described 12 . Briefly, mice were deeply anaesthetized with isoflurane, the fur was shaved, bupivacaine (5 mg/mL) was injected, and a 1cm incision was made over the ventral midline.…”

“…The corticospinal tract (CST) is a critical descending pathway for modulating dexterous motor control and afferent fiber inhibition 9–11 . Damage to the CST results in immediate loss of precise motor control 12–14 , and impairs behavioral responses to light touch and mechanical allodynia 15 . These multifaceted roles in control of both movement and sensory processing rely on its anatomical connections with distinct populations of interneurons within the spinal cord 16–18 .…”

Corticospinal Modulation of Precision Movements

“… 1 These structural changes are also reflected in an increase in newly formed task-related spines on excitatory layer 2/3 neurons. 2 Our recent study (Serradj et al) 3 sought to define the role of corticospinal neuron activity during the learning of a prehension task that requires precise movement modulation.…”

“… 15 Further study is necessary to determine how perturbation of S1 or related circuits affect the adaptive and precision tasks used in our recent study. 3 However, both tasks require the use of similar prehension movements and thus likely engage similar M1 and S1 neurons. Therefore, these two versions of the isometric pull task may prove useful in dissociating motor and sensory aspects of automated gross movement execution from precise control.…”

Effects of noninvasive neuromodulation targeting the spinal cord on early learning of force control by the digits

“… 21 One consideration as it pertains motor skill (re)acquisition is how neuromodulation targeting synapses linking descending motor commands onto the final common pathway might interact with task repetition to influence learning. Distinct patterns of temporal coding by corticospinal neurons underlie acquisition of task‐specific limb movements in rodent models, 22 and invasive neuromodulatory strategies shown to enhance re‐learning of functions compromised by neurological injury involve plasticity mechanisms unique to circuits engaged during task‐specific behavior. 23 It therefore stands to reason that administering PCMS against the backdrop of task‐specific activity may have some effect on early motor skill learning in humans; at least in those who show an upregulation of corticospinal transmission with the same dose of stimulation.…”