Serotonin has long been regarded as a food signal because serotonin mimics food in controlling behaviors, such as feeding, egg laying, and locomotion. However, serotonin depletion only moderately decreases feeding rate on food and does not noticeably affect development or brood size. This suggests that serotonin may not function as a major food signal, but function to enhance feeding under certain conditions. Here, we report that serotonin from ADF neurons enhances feeding in response to previously experienced food by activating serotonin receptor, SER-7, probably in MC and M4 pharyngeal motor neurons. Feeding rate of
tph-1 , which can''t synthesize serotonin, decreased to 75% of N2.
tph-1 expression in ADF neurons fully restored feeding rates of both
tph-1 and
mod-5;
tph-1, suggesting that ADF neurons release serotonin and activate feeding. Consistent with this, laser ablation of ADF neurons decreased feeding rate comparable to
tph-1. We also found that serotonin from ADF neurons enhances feeding via SER-7. Like
tph-1, feeding rates of both
ser-7 and
tph-1;
ser-7 decreased to 75% of N2, which suggests that SER-7 is the major receptor through which serotonin enhances feeding. SER-7 probably in MC and M4 neurons activate pharyngeal pumping and isthmus peristalsis rate, respectively. Then, under what conditions does serotonin enhance feeding? Previous studies suggested that ADF neurons sense food. Furthermore, it was reported that serotonin from ADF neurons enables worms to remember previously experienced food. It was also shown that serotonin from ADF neurons suppresses DAF-16 mediated stress response, which is crucial for survival on pathogenic bacteria such as PA14. These studies, taken together with our observation that serotonin from ADF enhances feeding, suggest that serotonin enhances feeding only in response to previously experienced and safe food. In fact, our preliminary results strongly support this hypothesis. On previously experienced food, feeding rate of
ser-7 decreased to 75% of N2, suggesting that serotonin signal is on. On the contrary, on previously unexperienced food, feeding rates of N2 and
ser-7 were only marginally different, suggesting that serotonin signal is off. Interestingly, feeding rate of N2 was significantly higher on familiar food than on unfamiliar food, further supporting our hypothesis. From these results, we suggest that only in response to familiar food, serotonin is released from ADF neurons and enhances feeding. We speculate that serotonin serves as a safeguard in the natural habitat filled with possible pathogens by promptly activating feeding only in response to previously experienced- and safe food.