A conserved neuropeptide system links head and body motor circuits to enable adaptive behavior

Abstract

Neuromodulators promote adaptive behaviors in response to either environmental or internal physiological changes. These responses are often complex and may involve concerted activity changes across circuits that are not physically connected. It is not well understood how neuromodulatory systems act across circuits to elicit complex behavioral responses. Here we show that the C. elegans NLP-12 neuropeptide system shapes responses to food availability by selectively modulating the activity of head and body wall motor neurons. NLP-12 modulation of the head and body wall motor circuits is generated through conditional involvement of alternate GPCR targets. The CKR-1 GPCR is highly expressed in the head motor circuit, and functions to enhance head bending and increase trajectory reorientations during local food searching, primarily through stimulatory actions on SMD head motor neurons. In contrast, NLP-12 activation of CKR-1 and CKR-2 GPCRs regulates body bending under basal conditions, primarily through actions on body wall motor neurons. Thus, locomotor responses to changing environmental conditions emerge from conditional NLP-12 stimulation of head or body wall motor neuron targets.

Increased dopaminergic neurotransmission results in ethanol dependent sedative behaviors in Caenorhabditis elegans

“…increased turning frequency for local search, but on prolonged deprivation of food their behavior changes to long runs and dispersal resulting in decreased amplitude [38,69]. We tested a NLP-12(OE) line and found that similar to what was seen previously, the NLP-12(OE) line showed an increase in amplitude of body bends within 30 min off food ( [38,68] Previous studies have shown that NLP-12 peptides function through their receptor CKR-2 in cholinergic motor neurons [37,63,64]. In order to test if CKR-2 is involved in the EIS behavior seen in dop-2 mutants, we tested both ckr-2 and ckr-2; dop-2 double mutants in the EtOH assay.…”

“…These data indicate that the increased dopamine seen in dop-2 mutants, signals through DOP-1, increasing NLP-12 release, which in turn functions through CKR-2. Studies have shown that CKR-2 is expressed in motor neurons in the head and along the body of the animal [37,68]. Here we speculate that DOP-2 could be functioning through CKR-2 present on cholinergic motor neurons that are in proximity to the DVA neuron.…”

“…We found that all three NLP-12 overexpression (OE) lines showed the EIS behavioral phenotype similar to that seen in dop-2 mutants (Fig 5E and 5F and S9 Movie). Previous studies have shown that loss of nlp-12 results in decreased depth of body bends while NLP-12(OE) lines show increased body bend depth in the absence of EtOH [38,[65][66][67][68]. In order to ascertain these contrasting phenotypes shown by overexpression of NLP-12 in the presence and absence of EtOH, we first tested WT and the NLP-12(OE) strains without EtOH and food to ascertain baseline controls.…”

“…In order to test if the EIS phenotype caused by NLP-12(OE) is also functioning through CKR-2, we made mutants of the NLP-12(OE) line with the ckr-2 mutation and tested these animals for the EIS phenotype. Here again we found that ckr-2 suppressed the EIS phenotype caused by NLP-12(OE) (S6E and S6F Fig) . In a recent study by Ramachandran et al (2020), it has been suggested that NLP-12 also functions through the CKR-1 receptor. Hence, we went on to test ckr-1 mutants for suppression of the dop-2 EIS phenotype.…”

Cholecystokinin/sulfakinin peptide signaling: conserved roles at the intersection between feeding, mating and aggression

“…In C. elegans the NPL-12a and 12b peptides only display weak sequence similarities to CCK (see Fig. 1 ), but activate two GPCRs related to CCK receptors (T23B3.4 and Y39A3B.5) [ 25 , 93 ], suggesting the presence of CCK-type signaling in this worm.…”