Defects in serotonin regulation in humans have been linked to several behavioural problems such as obesity, depression and addiction. How serotonin affects human behaviours is unclear, but studies on animals might shed some light on this. Reporting in the Proceedings of the National Academy of Sciences, Chao and colleagues show that, in the nervous system of Caenorhabditis elegans, serotonin can signal the presence of food and lead to rapid and reversible changes in the worm's avoidance of the noxious odour of octanol.

Wild-type C. elegans respond to undiluted octanol in three seconds by initiating backward movement regardless of feeding status. When diluted octanol is used, they respond more slowly in the absence of food ('off food') than when food is present ('on food'). The authors found that tph-1 null mutants, which show defects in serotonin biosynthesis, responded poorly to low concentrations of octanol even in the presence of food. Conversely, mod-5 mutants, which have increased serotonin levels, were hypersensitive to diluted octanol off food. Chao et al. then removed subpopulations of sensory neurons by laser microsurgery and found that ASH, but not ADL or AWB, neurons are responsible for detecting diluted octanol both on and off food. Serotonin signalling was mediated by a Gα protein encoded by gpa-11, as gpa-11 null mutants responded poorly to diluted octanol on and off food.

Detecting undiluted octanol, however, is more complicated. Although worms can normally sense undiluted octanol equally well on and off food, mutant worms with ASH neurons removed by laser microsurgery fail to respond to undiluted octanol on food. By contrast, the avoidance of undiluted octanol off food can only be abolished when ADL and AWB neurons are also ablated. These data indicate that ASH neurons are mainly responsible for sensing undiluted octanol on food, and that all three types of neurons are involved when off food. Interestingly, the authors found that serotonin is important under both conditions, although different signalling pathways might be activated depending on feeding status. In the absence of food, serotonin induces avoidance behaviours and requires the postsynaptic glutamate receptor GLR-1. Neither GLR-1 nor GPA-11 is involved in detecting undiluted octanol on food, and Chao and colleagues are still trying to identify the signalling components that are activated by serotonin under this condition.

It is intriguing that worms use different strategies to detect noxious stimuli depending on the strength of the signals and their feeding status. Whether this finding can help to explain serotonin-mediated behaviours in vertebrates remains to be seen.