| Scientists have long been fascinated by how anatomical structures in the brain can generate the diversity of behaviors apparent in the animal kingdom. While the ultimate goal of neuroscience is to understand complex brain function, the detailed mechanisms of even basic operational principles remain elusive. Larval zebrafish are an ideal system to investigate how ensembles of neurons integrate sensory information to produce simple behaviors. Among the most vital behaviors for the larvae's survival is the ability to evade predators. The escape response is mediated by a specialized neural circuit, which requires exceptional speed, robustness and flexibility. At the heart of its computation is a pair of giant neurons in the fish's hindbrain, the Mauthner cells.;When faced with aversive stimuli, a single action potential in the Mauthner cell is transmitted directly to motoneurons, producing a stereotyped escape sequence. Reliable activation of the Mauthner cell is a challenge due to its unusual biophysical properties. The main source of excitation was thought to originate directly from sensory nerves. My work identifies a secondary, convergent excitatory pathway composed of spiral fiber interneurons, which is essential for the robust activation of the Mauthner-cell-mediated escape circuit. Using functional imaging, I found that spiral fiber neurons respond to aversive sensory stimuli that can elicit escape responses. Laser-mediated ablations of the spiral fiber neurons largely eliminate Mauthner-cell-mediated escapes, suggesting that spiral fiber neurons play a pivotal role in this behavior. Conversely, activating these interneurons using optical techniques enhances the probability of escapes.;By exciting the Mauthner cell at the axon hillock, the site of action potential generation, spiral fiber neurons solve the challenge of overcoming the Mauthner cell's activation barrier. Additionally, this anatomically indirect, slower input may help to filter noise and prevent unnecessary firing of the Mauthner cell.;My research is the first to show the central role of a convergent excitatory pathway for a startle behavior. This motif, which can enhance the controllability and flexibility of behavior, is likely to be prevalent in other neural networks. |
