A Conserved Dopamine-Cholecystokinin Signaling Pathway Shapes Context–Dependent Caenorhabditis elegans Behavior

摘要

An organism's ability to thrive in changing environmental conditions requires the capacity for making flexible behavioral responses. Here we show that, in the nematode Caenorhabditis elegans , foraging responses to changes in food availability require nlp-12 , a homolog of the mammalian neuropeptide cholecystokinin (CCK). nlp-12 expression is limited to a single interneuron (DVA) that is postsynaptic to dopaminergic neurons involved in food-sensing, and presynaptic to locomotory control neurons. NLP-12 release from DVA is regulated through the D1-like dopamine receptor DOP-1, and both nlp-12 and dop-1 are required for normal local food searching responses. nlp-12 /CCK overexpression recapitulates characteristics of local food searching, and DVA ablation or mutations disrupting muscle acetylcholine receptor function attenuate these effects. Conversely, nlp-12 deletion reverses behavioral and functional changes associated with genetically enhanced muscle acetylcholine receptor activity. Thus, our data suggest that dopamine-mediated sensory information about food availability shapes foraging in a context-dependent manner through peptide modulation of locomotory output. Author Summary Animal behavior is profoundly affected by contextual information about the internal state of the organism as well as sensory information about the external environment. A class of signaling molecules known as neuropeptides have been implicated in driving transitions between behavioral states (e.g., from food seeking to satiety and back) but we have only a limited understanding of how neuropeptide signaling modulates neural circuit activity and elicits context-dependent behaviors. Here we identify a novel mechanism by which C. elegans modulate their behavior in response to sensory information about food. We show that dopaminergic regulation of NLP-12, a C. elegans homolog of the mammalian neuropeptide cholecystokinin (CCK), shapes behavioral transitions that are central to food searching. Given the conserved nature of these signaling pathways, our work raises the interesting possibility that dopamine modulation of CCK signaling represents a general mechanism by which nervous systems shape context-dependent behavioral changes.