Serotonin mediates food-odor associative learning in the nematode Caenorhabditis elegans

Abstract

We demonstrate that Caenorhabditis elegans is able to form an association between the presence of the odorant benzaldehyde and the food content of its environment. When exposed to 100% benzaldehyde for 1 h in the absence of food the naive attractive response is reduced, and we have found that this olfactory adaptation is attenuated by the presence of food. Contrary to nonassociative (single stimulus) learning theory, this response is not a function of the total time of exposure to benzaldehyde but rather an associative function of the ability of benzaldehyde to predict a nutrient-deficient environment. Genetic and pharmacological evidence revealed that the effects of food in this learning paradigm are mediated by serotonergic signaling. Food is a powerful motivator for animals, and many behaviors depend on food availability and recent nutritional history. For the nematode Caenorhabditis elegans, the presence of Escherichia coli, the standard laboratory food source, modulates multiple behaviors including locomotion, egg laying, and pharyngeal pumping (1, 2). In addition to these acute modulatory effects, food deprivation has been shown to alter more complex behavioral phenomena such as thermotaxis (3) and chemotaxis (CTX; ref. 4), and prolonged starvation can lead to the expression of an alternative developmental pathway leading to a period of relative metabolic stasis, the dauer larva stage (5). Food also has been used as an unconditioned stimulus (US) in associativelearning paradigms. Differential pairing of food with watersoluble chemoattractants (e.g., Na ϩ or Cl Ϫ ) leads to associative conditioning such that ions recently paired with food (CS ϩ ion) are preferred to ions that have not been paired recently with food (CS Ϫ ion; ref. 6).Food is clearly a salient environmental cue for C. elegans, and it is likely that nematodes use odor cues to locate food and avoid detrimental environments. C. elegans utilizes six primary sensory neurons to respond to more than 40 different volatile attractants and repellents (7). Prolonged exposure to some odorants leads to a decrease in the level of attraction to that specific odorant because of a phenomenon called olfactory adaptation (8). For example, exposure to benzaldehyde for 1 h causes a significant decrease in subsequent chemotactic scores. Adaptation in this context is used to refer to a behavioral response rather than its mechanisms. Previous investigations into this behavioral response have demonstrated that the reduction of CTX is susceptible to dishabituation, confirming that it is not the result of fatigue in sensory or motor systems but rather the result of a learning process (9). Indeed, prolonged exposure to a high concentration of benzaldehyde leads to the development of an aversive response to the odorant such that the animals will actively avoid a point source of benzaldehyde. This behavioral switch is produced by the dynamic interaction of two separate (attractive and aversive) benzaldehyde-responsive motivational systems (9).We investigated the relation...

Ethological analyses of crayfish behavior: a new invertebrate system for measuring the rewarding properties of psychostimulants

“…[12,33,40,45]) and, furthermore, supported the hypothesis that such studies may tap into fundamental neurobiological alterations that underlie drug addictions [7,33,58,65]. It demonstrated that a psychostimulant drug of abuse could be rewarding to an animal that, unlike mammalian species, exhibits a relatively simple neuronal organization.…”

“…Moreover, had crayfish used such contrast features to distinguish between the two environments provided during the CPP experiments, the striped environment may have been perceived as relatively novel (compared to the uniform nature of the other environment in the aquarium or their home container). In this respect, novelty has been strongly implicated in the susceptibility of stimuli to conditioning phenomena [10,16,34,45]. Most importantly, however, the contextual dependence of psychostimulant reward in crayfish can be tested in future experiments.…”

“…Electrical stimulation [5], biogenic amines [40] or food items [45] have served as rewards in past studies of invertebrates and in some cases there has since been considerable advance into understanding the underlying proximate mechanisms of such processes (e.g., ref. [12]).…”

An elegant mind: Learning and memory in Caenorhabditis elegans

“…Consistent with this role, exogenous serotonin inhibited habituation to benzaldehyde in the absence of food. Furthermore, the presence of food had no effect on the habituation of serotonin deficient mutants, cat-4 and tph-1 (Nuttley et al 2002). Following odorant habituation, expression of the learned behavior can be modulated by contextual cues present during conditioning.…”

“…Nuttley et al (2002) showed that habituation to benzaldehyde was inhibited in the presence of food. This suggests a learned association, making worms less likely to ignore benzaldehyde if it is predictive of food.…”