Faculty Opinions recommendation of Ephrin-B3 is the midline barrier that prevents corticospinal tract axons from recrossing, allowing for unilateral motor control.

Although motor deficits in humans with diabetic neuropathy have been extensively researched, its effect on the motor system is thought to be lesser than that on the sensory system. Therefore, motor deficits are considered to be only due to sensory and muscle impairment. However, recent clinical and experimental studies have revealed that the brain and spinal cord, which are involved in the motor control of voluntary movement, are also affected by diabetes. This review focuses on the most important systems for voluntary motor control, mainly the cortico-muscular pathways, such as corticospinal tract and spinal motor neuron abnormalities. Specifically, axonal damage characterized by the proximodistal phenotype occurs in the corticospinal tract and motor neurons with long axons, and the transmission of motor commands from the brain to the muscles is impaired. These findings provide a new perspective to explain motor deficits in humans with diabetes. Finally, pharmacological and non-pharmacological treatment strategies for these disorders are presented.

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Motor Control Via Spared Peri-infarct Corticospinal Tract in Patients With Pontine Infarct

Journal of Computer Assisted Tomography ◽

10.1097/rct.0b013e31814cf231 ◽

2008 ◽

Vol 32 (1) ◽

pp. 159-162 ◽

Cited By ~ 2

Author(s):

Ji-Won Park ◽

Seong Ho Kim ◽

Yong Woon Kim ◽

Jong Yeon Kim ◽

So Young Park ◽

...

Keyword(s):

Motor Control ◽

Corticospinal Tract ◽

Pontine Infarct

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In Vivo Recordings of Bulbospinal Excitation in Adult Mouse Forelimb Motoneurons

Journal of Neurophysiology ◽

10.1152/jn.00092.2004 ◽

2004 ◽

Vol 92 (3) ◽

pp. 1958-1962 ◽

Cited By ~ 47

Author(s):

Bror Alstermark ◽

Jun Ogawa

Keyword(s):

Motor Control ◽

Adult Mouse ◽

Corticospinal Tract ◽

Genetic Manipulation ◽

Medial Longitudinal Fasciculus ◽

Intracellular Recordings ◽

Descending Systems ◽

Monosynaptic Excitation

Here we report on pyramidal and reticulospinal excitation in forelimb motoneurons in the adult mouse using intracellular recordings in vivo. The results have been obtained in BALB/C mice, which were anesthetized with midazolam fentanyl/fluanison. In contrast to the rat, only weak and infrequent pyramidal excitation could be evoked with a minimal trisynaptic linkage. Disynaptic reticulospinal excitation could always be evoked, as well as monosynaptic excitation from the medial longitudinal fasciculus. The results suggest that the reticulospinal pathway in the mouse is important in voluntary motor control of the forelimbs and that the role of the corticospinal tract might be different in mouse compared with rat. Our study provides an opening for studying the effect of genetic manipulation on specified descending systems in the mouse in vivo.

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Motor command for precision grip in the macaque monkey can be mediated by spinal interneurons

Journal of Neurophysiology ◽

10.1152/jn.00089.2011 ◽

2011 ◽

Vol 106 (1) ◽

pp. 122-126 ◽

Cited By ~ 49

Author(s):

B. Alstermark ◽

L. G. Pettersson ◽

Y. Nishimura ◽

K. Yoshino-Saito ◽

F. Tsuboi ◽

...

Keyword(s):

Motor Control ◽

Sweet Potato ◽

Corticospinal Tract ◽

Index Finger ◽

Precision Grip ◽

Motor Command ◽

Macaque Monkey ◽

General View ◽

Macaque Monkeys ◽

Spinal Interneurons

In motor control, the general view is still that spinal interneurons mainly contribute to reflexes and automatic movements. The question raised here is whether spinal interneurons can mediate the cortical command for independent finger movements, like a precision grip between the thumb and index finger in the macaque monkey, or if this function depends exclusively on a direct corticomotoneuronal pathway. This study is a followup of a previous report (Sasaki et al. J Neurophysiol 92: 3142–3147, 2004) in which we trained macaque monkeys to pick a small piece of sweet potato from a cylinder by a precision grip between the index finger and thumb. We have now isolated one spinal interneuronal system, the C3-C4 propriospinal interneurons with projection to hand and arm motoneurons. In the previous study, the lateral corticospinal tract (CST) was interrupted in C4/C5 (input intact to the C3-C4 propriospinal interneurons), and in this study, the CST was interrupted in C2 (input abolished). The precision grip could be performed within the first 15 days after a CST lesion in C4/C5 but not in C2. We conclude that C3–C4 propriospinal interneurons also can carry the command for precision grip.

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Restoration of Direct Corticospinal Communication Across Sites of Spinal Injury

10.1101/546374 ◽

2019 ◽

Cited By ~ 2

Author(s):

Naveen Jayaprakash ◽

David Nowak ◽

Erik Eastwood ◽

Nicholas Krueger ◽

Zimei Wang ◽

...

Keyword(s):

Spinal Cord ◽

Motor Control ◽

Neural Progenitor Cells ◽

Corticospinal Tract ◽

Spinal Injury ◽

Combined Treatment ◽

Fine Motor ◽

Spinal Neurons ◽

Injury Site ◽

A Site

Injury to the spinal cord often disrupts long-distance axon tracts that link the brain and spinal cord, causing permanent disability. Axon regeneration is then prevented by a combination of inhibitory signals that emerge at the injury site and by a low capacity for regeneration within injured neurons. The corticospinal tract (CST) is essential for fine motor control but has proven refractory to many attempted pro-regenerative treatments. Although strategies are emerging to create relay or detour circuits that re-route cortical motor commands through spared circuits, these have only partially met the challenge of restoring motor control. Here, using a murine model of spinal injury, we elevated the intrinsic regenerative ability of CST neurons by supplying a pro-regenerative transcription factor, KLF6, while simultaneously supplying injured CST axons with a growth-permissive graft of neural progenitor cells (NPCs) transplanted into a site of spinal injury. The combined treatment produced robust CST regeneration directly through the grafts and into distal spinal cord. Moreover, selective optogenetic stimulation of regenerated CST axons and single-unit electrophysiology revealed extensive synaptic integration by CST axons with spinal neurons beyond the injury site. Finally, when KLF6 was delivered to injured neurons with a highly effective retrograde vector, combined KLF6/NPC treatment yielded significant improvements in forelimb function. These findings highlight the utility of retrograde gene therapy as a strategy to treat CNS injury and establish conditions that restore functional CST communication across a site of spinal injury.Significance StatementDamage to the spinal cord results in incurable paralysis because axons that carry descending motor commands are unable to regenerate. Here we deployed a two-pronged strategy in a rodent model of spinal injury to promote regeneration by the corticospinal tract, a critical mediator of fine motor control. Delivering pro-regenerative KLF6 to injured neurons while simultaneously transplanting neural progenitor cells to injury sites resulted in robust regeneration directly through sites of spinal injury, accompanied by extensive synapse formation with spinal neurons. In addition, when KLF6 was delivered with improved retrograde gene therapy vectors, the combined treatment significantly improved forelimb function in injured animals. This work represents important progress toward restoring regeneration and motor function after spinal injury.

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