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(l) Alex Schier, and Alix Lacoste

Knock on a tank of fish and you may observe that the animals suddenly change position. Blink, and you missed it. When fish perceive a threat in their environment, they produce an extraordinarily fast escape behavior: initial movement occurs within 5 milliseconds of a stimulus, and the entire escape sequence is over in just 1/3 of a second. This startle response is a common strategy among invertebrate and vertebrate species that enables them to avoid predatory attacks. Understanding how the brain mediates escape behaviors can provide clues into the architecture and logic of neural circuits in general: that is, how ensembles of neurons are organized to process sensory information and produce a particular behavioral output.
In zebrafish, the escape response is mediated by a neural circuit that requires exceptional speed, robustness and flexibility. At the heart of the escape network is a pair of giant neurons in the fish’s hindbrain, the Mauthner cells. A single firing event, or spike, in the Mauthner cell is correlated with an escape sequence away from aversive stimuli. Previous studies had suggested that sensory nerves are the main source of Mauthner excitation but research in the Schier and Engert labs has now identified a parallel and convergent pathway that is essential for Mauthner-cell-mediated escape.
In an article in Current Biology, Alix Lacoste with David Schoppik, Drew Robson, Martin Haesemeyer, Ruben Portugues, Jennifer Li, Owen Randlett and Caroline Wee describes this second pathway: it is composed of interneurons called spiral fiber neurons that excite the Mauthner cell at its axon hillock, a specialized location on a neuron where spikes are initiated. With functional imaging, they found that spiral fiber neurons are active in response to aversive sensory stimuli that can elicit escape responses. High-speed behavioral analysis and laser-mediated ablation experiments demonstrated that removing the spiral fiber neurons from the circuit largely eliminates Mauthner-cell-mediated-escapes. This suggests that spiral fiber neurons play a pivotal role in the escape behavior. Supporting this notion, the authors found that activating these interneurons using optical techniques enhances the probability of fish escaping.
These results indicate that an indirect interneuron pathway converges with a direct sensory pathway on the Mauthner cell to generate escapes. The control by parallel inputs renders the escape system more robust – the fish might only escape consistently when both pathways are activated – and extends the controllability of escapes by allowing the modulation of two separate pathways. Since this direct/indirect pathway architecture is also found in other organisms, the necessity of dual pathways might be a general motif of neural circuits.

Read more in Current Biology or download PDF






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