Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer).
Motor neurons project from the central nervous system to innervate muscle cells to either directly or indirectly control their activity. Contact between a motor neuron and muscle cell is usually via a specialized synapse called a neuromuscular junction.
Volitional motor control involves not only the initiation of desired movements but also the suppression of undesired movements. In this Opinion article, Ebbesen and Brecht argue that motor cortex neurons have a role in both aspects of motor control.
Amyotrophic lateral sclerosis (ALS) leads to selective loss of motor neurons. Using motor neurons derived from induced pluripotent stem cells from patients with ALS and FUS mutations, the authors demonstrate that axonal transport deficits that are observed in these cells can be rescued by HDAC6 inhibition.
The authors show that in a mouse model of spinal muscular atrophy (SMA), there is a reduction in sensory synaptic drive that leads to motor neuron dysfunction and motor behavior impairments. SMA motor neurons showed a lower surface expression of Kv2.1 potassium channels and reduced spiking ability. Increasing neuronal activity pharmacologically led to the normalization of Kv2.1 surface expression and an improvement in motor function.
The subtype of motor neurons that is most likely to degenerate early in amyotrophic lateral sclerosis is prone to endoplasmic reticulum (ER) stress in mice, owing to low levels of SIL1, an ER-associated protein.