Deconstruction of Corticospinal Circuits for Goal-Directed Motor Skills

Abstract

SUMMARY Corticospinal neurons (CSNs) represent the direct cortical outputs to the spinal cord and play important roles in motor control across different species. However, their organizational principle remains unclear. By using a retrograde labeling system, we defined the requirement of CSNs in the execution of a skilled forelimb food-pellet retrieval task in mice. In vivo imaging of CSN activity during performance revealed the sequential activation of topographically ordered functional ensembles with moderate local mixing. Region-specific manipulations indicate that CSNs from caudal or rostral forelimb area control reaching or grasping, respectively, and both are required in the transitional pronation step. These region-specific CSNs terminate in different spinal levels and locations, therefore preferentially connecting with the premotor neurons of muscles engaged in different steps of the task. Together, our findings suggest that spatially defined groups of CSNs encode different movement modules, providing a logic for parallel-ordered corticospinal circuits to orchestrate multistep motor skills.

Context-dependent limb movement encoding in neuronal populations of motor cortex

“…In everyday life we have to generate dexterous movements of limb joints to purposefully interact with variable environments. The mammalian primary motor cortex (M1) is known to contribute to control of dexterous limb movements [1][2][3][4][5][6][7][8] and gait modifications [9][10][11] . Moreover, M1 has recently been shown to have a pivotal function in learning nondexterous movement sequences in rats 12 , and has been suggested to be necessary for progressing though the steps of learned skilled forelimb movements in mice 7 .…”

Global connectivity and function of descending spinal input revealed by 3D microscopy and retrograde transduction

“…Coordinated activity in multiple tracts often converges on the same motor output. For example, distinct phases of targeted forelimb movement are controlled by different sets of corticospinal tract distributed through motor cortex, in coordination with other nuclei including the red nucleus and reticular formation (Alstermark et al, 2004;Esposito et al, 2014;Kuypers H. and Martin, 1982;Lemon, 2008;Siegel et al, 2015;Wang et al, 2017).…”

In-depth characterization of layer 5 output neurons of the primary somatosensory cortex innervating the mouse dorsal spinal cord

“…This finding is consistent with previous reports of labelling spinal interneurons targeted by CST neurons, showing that tracing from the motor cortex labels terminals mainly in the ventral and intermediate spinal cord, whereas tracing from S1 labels terminals in lamina III and IV of the dorsal horn. (Kamiyama T et al 2015;Wang X et al 2017;Ueno M et al 2018). The dorsal horn laminae III and IV contain interneurons that process touch and proprioceptive information.…”

“…In addition to the hindbrain, the cerebral cortex is a major source of descending input to the spinal cord (Lemon RN and J Griffiths 2005;Abraira VE et al 2017;Wang X et al 2017;Liu Y et al 2018;Ueno M et al 2018). Layer 5 pyramidal neurons of several cortical areas project to this site, including neurons residing in the motor and premotor cortices as well as in the somatosensory cortex (S1).…”