Zebrafish neuromuscular junction: The power of N

In the early 1950s, Katz and his colleagues capitalized on the newly developed intracellular microelectrode recording technique to investigate synaptic transmission. For study they chose frog neuromuscular junction (NMJ), which was ideally suited due to the accessibility and large size of the muscle cells. Paradoxically, the large size precluded the use of next generation patch clamp technology. Consequently, electrophysiological study of synaptic function shifted to small central synapses made amenable by patch clamp. Recently, however, the unique features offered by zebrafish have rekindled interest in the NMJ as a model for electrophysiological study of synaptic transmission. The small muscle size and synaptic simplicity provide the singular opportunity to perform in vivo spinal motoneuron-target muscle patch clamp recordings. Additional incentive is provided by zebrafish lines harboring mutations in key synaptic proteins, many of which are embryonic lethal in mammals, but all of which are able to survive well past synapse maturation in zebrafish. This mini-review will highlight features that set zebrafish NMJs apart from traditional NMJs. We also draw into focus findings that offer the promise of identifying features that define release sites, which serve to set the upper limit of transmitter release. Since its conception several candidates representing release sites have been proposed, most of which are based on distinctions among vesicle pools in their state of readiness for release. However, models based on distinctions among vesicles have become enormously complicated and none adequately account for setting an upper limit for exocytosis in response to an action potential (AP). Specifically, findings from zebrafish NMJ point to an alternative model, positing that elements other than vesicles per se set the upper limits of release.