Figure 3.

Interneuron pathology leads to an impaired excitation/inhibition balance in ALS. Lower motoneurons execute voluntary movements by integrating central descending and peripheral commands, and local inhibitory (GABAergic or glycinergic interneurons and Renshaw cells) and modulatory (cholinergic and serotonergic neurons) inputs. During the natural course of the disease, including prior to the first signs of clinical symptoms, dysfunctions and loss of the different classes of interneurons have been documented in the motor cortex and spinal cord of ALS patients and mouse models of the disease.