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

Abstract

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.

Locomotion Behavior Is Affected by the GαS Pathway and the Two-Pore-Domain K+ Channel TWK-7 Interacting in GABAergic Motor Neurons in Caenorhabditis elegans

“…Furthermore, hyperactive twk-7(null) and kin-2(cau1) mutants are characterized by reduced wave amplitudes during spontaneous crawling. In sharp contrast, hyperactive animals with elevated presynaptic acetylcholine release, such as egl-30(gf) and goa-1(lf) (Brundage et al 1996;Lackner et al 1999;Huang et al 2008), or increased postsynaptic acetylcholine receptor sensitivity (Bhattacharya et al 2014) moved with enhanced wave amplitudes. Although Ga q (gf) and Ga 0 (lf) animals are characterized by an increased spontaneous body-bending frequency on plates, these worms executed futile back-and-forth movements.…”

Excitatory neurons sculpt GABAergic neuronal connectivity in the C. elegans motor circuit

“…Plasmids were constructed using the two-slot Gateway Cloning system (Invitrogen) as described previously (Bhattacharya et al, 2014). him-4p::mCD8::GFP Entry vector: A him-4p promoter fragment (2156 bp) was amplified from pPRZ138.2 (a gift from Peter Roy, University of Toronto, ON, Canada) and cloned into pENTR-D-TOPO to create pENTR-3′-him4.…”

In the proper context: Neuropeptide regulation of behavioral transitions during food searching

“…[5][6][7][8] Here we will focus on recent work from our laboratory describing a requirement for the cholecystokininlike neuropeptide NLP-12 in a contextdependent C. elegans foraging behavior. 9 Changes in food availability are among the most variable and challenging environmental factors that animals face. Thus, mechanisms that regulate food-seeking behaviors are particularly important for survival.…”

“…Recently, we reported that the C. elegans neuropeptide NLP-12, a homolog of mammalian Cholecystokinin (CCK), coordinates behavioral responses to changes in food availability. 9 Specifically, we discovered that NLP-12 signaling is required for behavioral transitions into a local searching motor program that is triggered by removal from food. Immediately following removal from food wild type C. elegans alter their locomotory pattern by increasing high angle turning and restricting movement to their local environment (local or area-restricted search).…”

“…nlp-12 is solely expressed in the neuron DVA, 9,14,15 an interneuron that is wellpositioned to integrate sensory information and shape locomotory behavior. DVA is postsynaptic to PDE dopaminergic neurons that are involved in food-sensing, and presynaptic to both motor neurons and interneurons previously demonstrated to be involved in the control of movement 16 (Fig.…”