ALS has been modeled in mice that are transgenic for a variety of mutant forms of SOD1, allowing for the study of the trajectory of the condition at various time points (5, 6).
Among the studies conducted to date are a number addressing electrophysiological changes.
For the ex vivo alternative, slice physiology is challenging because most mouse models develop disease after 1 mo of age, a time when spinal cord tissue becomes more sensitive to ischemia (11, 12), making isolation of viable slices difficult.
In addition, the spinal cord becomes heavily myelinated in the first few weeks of postnatal life (13), making visualization of individual neurons difficult.
A major challenge to understanding spinal cord physiology of the mouse models of ALS arises from difficulty in distinguishing the individual features of neurons in the anatomically and physiologically heterogeneous motor system.
For example, the usefulness of in vivo recordings requires ensuring adequate sampling of anatomically and functionally heterogeneous spinal cord MNs.
In a G85R SOD1YFP transgenic mouse model of ALS, which becomes paralyzed by 5–6 mo, where MN cell bodies are fluorescent, enabling the same type of recording from spinal cord tissue slices, we observed that all four MN subtypes were present at 2 mo of age.