Abstract
Corticospinal motor neurons (CSMN) have a unique ability to receive, integrate, translate, and transmit the cerebral cortex's input toward spinal cord targets and therefore act as a “spokesperson” for the initiation and modulation of voluntary movements that require cortical input. CSMN degeneration has an immense impact on motor neuron circuitry and is one of the underlying causes of numerous neurodegenerative diseases, such as primary lateral sclerosis (PLS), hereditary spastic paraplegia (HSP), and amyotrophic lateral sclerosis (ALS). In addition, CSMN death results in long-term paralysis in spinal cord injury patients. Detailed cellular analyses are crucial to gain a better understanding of the pathologies underlying CSMN degeneration. However, visualizing and identifying these vulnerable neuron populations in the complex and heterogeneous environment of the cerebral cortex have proved challenging. Here, we will review recent developments and current applications of novel strategies that reveal the cellular and molecular basis of CSMN health and vulnerability. Such studies hold promise for building long-term effective treatment solutions in the near future.
Highlights
Our expertise in the precise control of fine movement sets us apart from other mammals
Among all other neuron types in the cerebral motor cortex, one neuron population stands out with its unique abilities and function. These neurons are characterized by: (1) a large pyramidal cell body, (2) a single apical dendrite that extends toward layer I displaying major branching and arborization, especially within layer II/III, (3) numerous basal dendrites arising from the basolateral surface, and most impressively (4) a very long axon that projects toward spinal cord targets (Molnar and Cheung, 2006; Ozdinler and Macklis, 2006; Molyneaux et al, 2007)
Injection of AAV1-eGFP into the motor cortex resulted in visualization of green fluorescent protein (GFP)+ axon fibers within corticospinal tract (CST), suggesting that a subset of corticospinal motor neurons (CSMN) were transduced, and the identity of transduced neurons were further demonstrated with paired retrograde labeling (Hutson et al, 2011)
Summary
Our expertise in the precise control of fine movement sets us apart from other mammals. Among all other neuron types in the cerebral motor cortex, one neuron population stands out with its unique abilities and function These neurons are characterized by: (1) a large pyramidal cell body, (2) a single apical dendrite that extends toward layer I displaying major branching and arborization, especially within layer II/III, (3) numerous basal dendrites arising from the basolateral surface, and most impressively (4) a very long axon that projects toward spinal cord targets (Molnar and Cheung, 2006; Ozdinler and Macklis, 2006; Molyneaux et al, 2007). The heterogeneity of these neurons in terms of somatodendritic morphology, axonal
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