New Study Reveals Key Differences Between Human and Mice Neuron-Muscle Connections

Scientists at the University of Edinburgh discovered that the human neuromuscular junction (NMJ) — a cell connection between neurons and muscle that enables motion — is different in size and structure than other mammals, including mice, which are routinely used in research.

“Our findings provide unique insights into the structure of the human nervous system, identifying features that set us apart from other mammals,” Tom Gillingwater, professor of anatomy at the University of Edinburgh’s Centre for Discovery Brain Sciences, who co-led the study, said in a press release.

This has not been reported previously and has the potential to deepen scientists’ understanding of diseases in which the function of NMJs is compromised.

The research, titled “Cellular and Molecular Anatomy of the Human Neuromuscular Junction,” was published in the scientific journal Cell Reports.

The central nervous system controls body movement by transmitting electrical and chemical signals from motor neurons to muscles, and the latter are responsible for eliciting motion that the signal codes for.

The cell connection between nerve cells and muscles is known as the neuromuscular junction.

Due to ethical reasons, it’s difficult to obtain human biopsy samples suitable for high-resolution cellular and molecular analysis. In this study, scientists developed an approach that allowed them to do just that.

Researchers used tissue samples from 20 patients, whose ages ranged from 34-92, and who underwent lower limb amputation due to a variety of clinical indications. The samples were obtained from healthy regions of the limb, and 2,860 NMJs from four different types of muscle — extensor digitorum longus, soleus, peroneus longus, and peroneus brevis  — were harvested.

Using high-resolution imaging techniques, the team compared human NMJs with those of mice. They found that human NMJs were significantly smaller, less complex, and more fragmented than in mice. Human NMJs also showed no signs of age-related degeneration.

Additionally, human NMJ proteins and molecular pathways exhibited different patterns of expression.

“The age-old adage of ‘seeing is believing’ is particularly fitting for this study. The human nerve connections that we saw – using new microscopy methods crucial for this study – were very different from what was previously thought,” said Christian Soeller, professor of physical cell biology at the University of Exeter’s Physics Department and Living Systems Institute, who co-led the study.

In future studies, the team will work to shed light on how the neuromuscular junction is compromised in movement disorders, such as amyotrophic lateral sclerosis.