Corticospinal Tract Development and Spinal Cord Innervation Differ between Cervical and Lumbar Targets

Abstract

The corticospinal (CS) tract is essential for voluntary movement, but what we know about the organization and development of the CS tract remains limited. To determine the total cortical area innervating the seventh cervical spinal cord segment (C7), which controls forelimb movement, we injected a retrograde tracer (fluorescent microspheres) into C7 such that it would spread widely within the unilateral gray matter (to Ͼ80%), but not to the CS tract. Subsequent detection of the tracer showed that, in both juvenile and adult mice, neurons distributed over an unexpectedly broad portion of the rostral two-thirds of the cerebral cortex converge to C7. This even included cortical areas controlling the hindlimbs (the fourth lumbar segment, L4). With aging, cell densities greatly declined, mainly due to axon branch elimination. Whole-cell recordings from spinal cord cells upon selective optogenetic stimulation of CS axons, and labeling of axons (DsRed) and presynaptic structures (synaptophysin) through cotransfection using exo utero electroporation, showed that overgrowing CS axons make synaptic connections with spinal cells in juveniles. This suggests that neuronal circuits involved in the CS tract to C7 are largely reorganized during development. By contrast, the cortical areas innervating L4 are limited to the conventional hindlimb area, and the cell distribution and density do not change during development. These findings call for an update of the traditional notion of somatotopic CS projection and imply that there are substantial developmental differences in the cortical control of forelimb and hindlimb movements, at least in rodents.

Differential innervation within a transverse plane of spinal gray matter by sensorimotor cortices, with special reference to the somatosensory cortices

“…A solution of AAV was injected into each cortical area, and after 2–3 weeks, the mice were sacrificed and cortical and spinal sections were cut. In each cortical area, strong native FP fluorescence was observed in the deep layers containing the C7‐projecting neurons (Kamiyama et al, ) (Figure b–f). In the cerebral cortex of rodents, motor and sensory representations of the forelimb areas partially overlap (Hall & Lindholm, ).…”

“…The heat map indicates the distribution area of C7‐projecting neurons. The map was modified from Kamiyama et al (). Each circle indicates an injection site.…”

“…This entailed analyzing the axonal distribution from CS neurons located in five cortical areas in mice after injecting replication-incompetent adeno-associated virus (AAV) serotype 1 vectors, which expressed membrane-tagged fluorescent proteins in the infected cells. Moreover, the results of a previous study (Kamiyama et al, 2015) enabled us to identify the precise boundary of the cortical areas containing CS neurons. The targeted cortical areas included both motor-related and somatosensory regions, but to avoid multiple labeling of axonal projections, we excluded the areas most densely packed with CS neurons in M1/S1 (Kamiyama et al, 2015).…”

The corticospinal tract: Evolution, development, and human disorders

“…Cortical Areas Contributing to the CST The majority of CST axons originate from pyramidal cells located in the inferior part of cortical layer V in the primary motor and sensory cortex (M1 and S1), while other cortical regions make smaller contributions (Nudo and Masterton, 1990). In rodents, CST axons originate from motor, somatosensory, parietal, cingulate, visual, and prefrontal regions (Miller, 1987;Akintunde and Buxton, 1992;Tennant et al, 2011;Kamiyama et al, 2015). In cats, M1, S1, as well as the secondary sensorimotor cortices (S2), make major contributions to the CST (Armand and Kuypers, 1980).…”

Deconstruction of Corticospinal Circuits for Goal-Directed Motor Skills

“…However, in both primates and rodents, only a subset of neurons in cortical layer V are CSNs. Moreover, they are distributed over multiple cortical regions such as M1, M2 and S1, and in clusters such as the rostral forelimb area (RFA) and the caudal forelimb area (CFA) (Kamiyama et al, 2015; Nudo and Masterton, 1990). With conventional methods, previous studies could only analyze mixed subsets of cortical neurons including both CSNs and other cortical neurons.…”