Neuromodulatory State and Sex Specify Alternative Behaviors through Antagonistic Synaptic Pathways in C. elegans

Abstract

SUMMARY Pheromone responses are highly context-dependent. For example, the C. elegans pheromone ascaroside C9 (ascr#3) is repulsive to wild-type hermaphrodites, attractive to wild-type males, and usually neutral to “social” hermaphrodites with reduced activity of the npr-1 neuropeptide receptor gene. We show here that these distinct behavioral responses arise from overlapping push-pull circuits driven by two classes of pheromone-sensing neurons. The ADL sensory neurons detect C9, and in wild-type hermaphrodites, drive C9 repulsion through their chemical synapses. In npr-1 mutant hermaphrodites, C9 repulsion is reduced by the recruitment of a gap junction circuit that antagonizes ADL chemical synapses. In males, ADL sensory responses are diminished; in addition, a second pheromone-sensing neuron, ASK, antagonizes C9 repulsion. The additive effects of these antagonistic circuit elements generate attractive, repulsive or neutral pheromone responses. Neuronal modulation by circuit state and sex, and flexibility in synaptic output pathways, may permit small circuits to maximize their adaptive behavioral outputs.

Dissection of neuronal gap junction circuits that regulate social behavior in Caenorhabditis elegans

“…ADL neurons were subjected to a series of five ascr#3 pulses, a protocol that assessed sensory adaptation and recovery as well as the initial sensory response. In agreement with previous studies (43), the ADL responses of N2 adapted more quickly than those of npr-1 (t 1/2 ∼3.6 s for N2 vs. 9.2 s for npr-1) and recovered less between successive ascr#3 pulses (Fig. 5A).…”

“…Sensory responses to oxygen levels also involved RMG, URX, and other neurons. Some of these responses are rapidly modified by acute expression of npr-1 from a heat shock u un n nc c c c 1 1 1( ( ( (w w w wt t) t) promoter, suggesting that they are acute and primary readouts of circuit activity (40,43). The results of these experiments help to distinguish between alternative models of RMG circuit function.…”

Genetic mapping of variation in dauer larvae development in growing populations of Caenorhabditis elegans

“…Dauer pheromone, a complex mix of structurally related ascarosides (Jeong et al, 2005;Butcher et al, 2007;Pungaliya et al, 2009;Park et al, 2012), is used by C. elegans to assess population density, with these ascarosides also acting to regulate aggregation, mate recognition and dispersal (Srinivasan et al, 2008;Harvey, 2009;Pungaliya et al, 2009;Izrayelit et al, 2012;Jang et al, 2012). Although there is an extensive and detailed understanding of the genetic pathways that specify dauer and non-dauer larval development in C. elegans (see Hu (2007) for a review), the ecology of the species is still poorly understood.…”

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

“…Several recent studies utilizing invertebrate model organisms have started to address these questions. [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.…”