Removing a single neuron in a vertebrate brain forever abolishes an essential behavior

Significance The Mauthner cell is the largest neuron known in the vertebrate brain and, in fish, mediates rapid escape behavior. Ablating this neuron has repeatedly failed to eliminate rapid escapes, a survival role of these escapes has not been supported experimentally, and it is unknown which advantage the enormous size and complexity of the cell conveys. By taking care to ensure ablations remove not only the soma but also the giant axon, we find that rapid escapes are lost forever and that this loss directly affects survival in predator–prey assays. The Mauthner cell thus is an example in which a survival-critical function depends on an individual neuron whose axon appears to have unusual capacities to remain functional after severe injury.

The giant Mauthner (M) cell is the largest neuron known in the vertebrate brain. It has enabled major breakthroughs in neuroscience but its ultimate function remains surprisingly unclear: An actual survival value of M cell-mediated escapes has never been supported experimentally and ablating the cell repeatedly failed to eliminate all rapid escapes, suggesting that escapes can equally well be driven by smaller neurons. Here we applied techniques to simultaneously measure escape performance and the state of the giant M axon over an extended period following ablation of its soma. We discovered that the axon survives remarkably long and remains still fully capable of driving rapid escape behavior. By unilaterally removing one of the two M axons and comparing escapes in the same individual that could or could not recruit an M axon, we show that the giant M axon is essential for rapid escapes and that its loss means that rapid escapes are also lost forever. This allowed us to directly test the survival value of the M cell-mediated escapes and to show that the absence of this giant neuron directly affects survival in encounters with a natural predator. These findings not only offer a surprising solution to an old puzzle but demonstrate that even complex brains can trust vital functions to individual neurons. Our findings suggest that mechanisms must have evolved in parallel with the unique significance of these neurons to keep their axons alive and connected.