The Cortical "Upper Motoneuron" in Health and Disease.

Area of Science:

• Neuroscience
• Motor Control
• Evolutionary Biology

Background:

• Upper motoneurons (UMNs) control spinal and cranial mechanisms via the corticospinal tract (CST) and brainstem pathways.
• The primate corticospinal system exhibits diverse origins and fiber sizes, with large fibers unique to larger primates.
• Direct cortico-motoneuronal (CM) projections to arm/hand motoneurons are an advanced evolutionary trait, prominent in humans.

Purpose of the Study:

• To review the organization and evolutionary aspects of the corticospinal system.
• To highlight the role of the corticospinal system, particularly CM projections, in Amyotrophic Lateral Sclerosis (ALS).
• To emphasize the need for appropriate animal models reflecting human corticospinal system function in disease.

Main Methods:

• Review of existing literature on corticospinal tract (CST) and cortico-motoneuronal (CM) projections.
• Analysis of evolutionary development of primate motor pathways.
• Examination of evidence linking corticospinal system dysfunction to early stages of ALS.

Main Results:

• CM projections originate from specific cortical areas ('new' M1, area 3a) and involve neurons with varying axon conduction velocities.
• Corticospinal neurons exhibit distinct organization and recruitment patterns during movement compared to lower motoneurons.
• Strong evidence suggests the corticospinal system, especially CM projections to limb muscles, is involved in early ALS pathogenesis.

Conclusions:

• The human corticospinal system, with its unique CM projections, plays a significant role in fine motor control and is implicated in ALS.
• Species-specific differences in corticospinal system organization necessitate careful consideration when selecting animal models.
• Further research using relevant animal models is essential for understanding and treating human corticospinal disorders like ALS.