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

Neuromodulation enables transient restructuring of anatomically fixed neural circuits, generating alternate outputs and distinct states that allow for flexible organismal responses to changing conditions. We recently identified a requirement for the neuropeptide-like protein NLP-12, a Caenorhabditis elegans homolog of mammalian Cholecystokinin (CCK), in the control of behavioral responses to altered food availability. We showed that deletion of nlp-12 impairs turning during local food searching while nlp-12 overexpression is sufficient to induce deep body bends and enhance turning. nlp-12 is solely expressed in the DVA interneuron that is located postsynaptic to the dopaminergic PDE neurons and presynaptic to premotor and motor neurons, well-positioned for modulating sensorimotor tasks. Interestingly, DVA was previously implicated in a NLP-12 mediated proprioceptive feedback loop during C. elegans locomotion. Here, we discuss the modulatory effects of NLP-12 with an emphasis on the potential for circuit level integration with olfactory information about food availability. In addition, we propose potential mechanisms by which DVA may integrate distinct forms of sensory information to regulate NLP-12 signaling and mediate context-dependent modulation of the motor circuit.