Integrating postsynaptic morphology and dynamics to evaluate neuromuscular synapse status: Insights from...

The neuromuscular junction (NMJ) is a crucial peripheral synapse that controls muscle contraction. It consists of a presynaptic motor terminal, a postsynaptic muscle domain, and associated cells, such as terminal Schwann cells and kranocytes. Its larger size compared to central synapses has allowed detailed analyses of NMJ morphology that have been widely used as a reliable parameter of synaptic formation, maturation, function, and decline. Due to its high affinity for postsynaptic acetylcholine receptors (AChRs), the snake venom-derived α-bungarotoxin (BTX) has been pivotal in advancing our understanding of NMJ organization, enabling a detailed mapping of postsynaptic morphologies associated to distinct functional outcomes. Although certain morphological features are often associated with NMJ worsening, some of these cellular changes also occur in biological contexts where synaptic function remains intact. In this review, we draw on previous studies and our recent findings using BTX-based pulse-chase assays to suggest that combining morphological analyses with assessments of postsynaptic stability offers a more comprehensive understanding of NMJ function and regenerative potential. We propose that integrating diverse BTX-based tools into studies of NMJ morphology and stability will provide particularly valuable insights in contexts such as aging, injury, and neuromuscular diseases, where these combined parameters may serve as robust predictors of functional outcomes.