A conserved dopamine-cholecystokinin signaling pathway shapes context-dependent Caenorhabditis elegans behavior

• Published in: PLoS genetics Vol. 10; no. 8; p. e1004584
• Main Authors: Bhattacharya, Raja, Touroutine, Denis, Barbagallo, Belinda, Climer, Jason, Lambert, Christopher M, Clark, Christopher M, Alkema, Mark J, Francis, Michael M
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.08.2014; Public Library of Science (PLoS)
• Subjects: Animal behavior; Animals; Behavior, Animal; Biology and Life Sciences; Caenorhabditis elegans; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Cholecystokinin; Cholecystokinin - genetics; Cholecystokinin - metabolism; Dopamine; Dopamine - genetics; Dopamine - metabolism; Dopamine receptors; Dopaminergic Neurons; Food; Foraging behavior; Genetic aspects; Genetic engineering; Health aspects; Mutation; Nematodes; Neurons; Neuropeptides; Phenols; Physiological aspects; Receptors, Dopamine; Receptors, Dopamine D1 - genetics; Receptors, Dopamine D1 - metabolism; Rodents; Signal Transduction - genetics; Studies; Synaptic Transmission
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1004584

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.