In order to survive and reproduce, animals have to respond appropriately to changes in their environment by adapting behaviours such as feeding, locomotion, foraging for food and egg-laying. Studies on C. elegans have shown that neuropeptides can signal these changes and so influence the behavioural state of the worm. For example, neuropeptides encoded by the
flp-1 gene have a role in switching off egg-laying in the absence of food. We are interested in the role of Neuropeptide Y-like receptors (NPRs) in the regulation of worm behaviour. Here we present work on the role of NPR-2 in the control of movement.. We have investigated the role of
npr-2 using deletion allele
ok419, a putative null. The
npr-2 mutant moves slowly (~50 % of wild type rate) and is uncoordinated, both on plates and in liquid thrashing assays. Furthermore,
npr-2 animals are resistant to the acetylcholine esterase inhibitor aldicarb. We have carried out reporter expression studies for
npr-2 and these show that the gene is expressed in neurones in the head and nerve cord, probably in a subset of cholinergic motorneurones. This strongly suggests that NPR-2 facilitates movement, probably through facilitation of ACh release at the neuromuscular junction.. We further asked whether a closely related NPY-like receptor, NPR-1, also contributes to the coordination of movement as it is expressed in the GABAergic motorneurones (1). The NPR-1 receptor has been implicated in social feeding behaviour (2). We carried out a genetic analysis of the
npr-2 mutation in combination with different alleles of
npr-1. This analysis showed that the locomotion defects are only apparent in an
npr-1 gain of function (F215V) background found in N2 animals. Thus, NPR-2 and NPR-1 play an antagonisitc role in the regulation of movement. We propose a model where NPR-1 215V inhibits and NPR-2 facilitates movement, either directly or by inhibiting NPR-1 215V. We are currently investigating whether NPR-2 and NPR-1 also have a role in regulating feeding. We would further like to know what the environmental cue is that activates the NPR-2 signalling pathway.. We thank the BBSRC for financial support and the C. elegans Knockout Consortium, CGC and Mario de Bono for strains.