In the grand scheme of the animal kingdom, insects are often overlooked for their impressive locomotor skills. They can walk forwards, backwards and even upside down, traversing challenging environments with relative ease. But how do insects achieve this coordination? Clare Howard (Columbia University) and colleagues teach us that the insect nervous system employs a multifaceted signalling network to optimize their speed, gait and reaction timing to gracefully navigate through life.

Using the vinegar fly (Drosophila melanogaster), Howard and colleagues surveyed the fly nervous system to establish the sequence of signals involved in locomotion. The neural circuits responsible aggregate in the ventral nerve cord, their equivalent of the vertebrate spinal cord. The ventral nerve cord is the remote control driving the fly's three pairs of legs and it is so in tune with the fly's movements that it can even stimulate typical leg behaviours, such as walking and grooming, after a fly has been decapitated. But how does the ventral nerve cord control fly movements on such a fine scale? The authors looked to the body's built-in messaging system – the neuromodulators – to obtain the answer. Neuromodulators, such as serotonin, dopamine and noradrenaline (norepinephrine), work to transmit signals about the environment to the nervous system for processing, which are then sent back to the limbs to trigger an appropriate response.

First, the authors manipulated the fly's genetics to activate neurons associated with each of the major neuromodulators. Surprisingly, fly walking speed only shifted when the serotonergic system was activated, with no changes observed in any of the other neuromodulators. In the flies with serotonergic activation, walking remained consistently slower and straighter than in normal flies, providing credible evidence for the role of serotonin in their agility. To confirm a direct link between serotonin and locomotion, the authors then altered the fly genes to turn off their serotonergic neurons, which caused them to walk faster and in more circuitous walking paths. Remarkably, the flies continued to walk more slowly when serotonin was activated regardless of the environment in which they were tested, with serotonin activation reducing walking speed even under varying temperatures, terrains, orientations and degrees of hunger.

Efficient movement is especially vital when predators attack. Many animals use their own unique version of ‘fight or flight’ at the first sign of a threat, ready to make a break for safety. Although these complex escape manoeuvres are typically attributed to higher vertebrates, such as mammals and fish, flies also display escape tactics in response to threatening stimuli, often beginning with a short freezing period that allows the fly to initiate the appropriate response. But the role of serotonin in dictating the fly's locomotor response to these threats was unknown. Howard and colleagues found that if serotonin is inhibited, flies fail to ‘freeze’ and think through their response, causing them to take longer to reach an appropriate walking speed when threatened. This change in behaviour when serotonin is lost could greatly increase their chance of being eaten, suggesting that serotonin acts as a locomotor hand-break and is an essential cog in the flies’ threat response machinery.

Excitingly, these findings provide evidence that insects use serotonin in much the same way as fish and mammals. As serotonin dictates movement in complex vertebrates, it is likely that this mechanism developed first in simpler animals, like insects, and subsequently evolved in the more complex species in which it is observed today. Thus, serotonin helps animals from flies to cats walk the straight and narrow through life.