Pheromones Modulate Learning by Regulating the Balanced Signals of Two Insulin-like Peptides

Abstract

Social environment modulates learning through unknown mechanisms. Here, we report that a pheromone mixture that signals overcrowding inhibits C. elegans from learning to avoid pathogenic bacteria. We find that learning depends on the balanced signaling of two insulin-like peptides (ILPs), INS-16 and INS-4, which act respectively in the pheromonesensing neuron ADL and the bacteria-sensing neuron AWA. Pheromone exposure inhibits learning by disrupting this balance: it activates ADL and increases expression of ins-16, and this cellular effect reduces AWA activity and AWA-expressed ins-4. The activities of the sensory neurons are required for learning and the expression of the ILPs. Interestingly, pheromones also promote the ingestion of pathogenic bacteria while increasing resistance to the pathogen. Thus, the balance of the ILP signals integrates social information into the learning process as part of a coordinated adaptive response that allows consumption of harmful food during times of high population density.

Neuromodulatory pathways in learning and memory: Lessons from invertebrates

“…Besides food context, social context has been widely shown to influence learning in diverse animals. Crowding reduces associative learning in C. elegans and L. stagnalis 119‐121 . In C. elegans , this phenomenon is initiated by pheromone detection and involves insulin‐like peptide signalling, as well as signalling through the C. elegans homologue of the elevenin neuropeptide SNET‐1 (Figure 4A).…”

“…In C. elegans , this phenomenon is initiated by pheromone detection and involves insulin‐like peptide signalling, as well as signalling through the C. elegans homologue of the elevenin neuropeptide SNET‐1 (Figure 4A). 119,120 Social context also affects learning in the honeybee A. mellifera . Queen mandibular pheromone reduces associative learning in worker bees by suppressing juvenile hormone synthesis.…”

“…Crowding reduces associative learning in C. elegans and L. stagnalis. [119][120][121] In C. elegans, this phenomenon is initiated by pheromone detection and involves insulinlike peptide signalling, as well as signalling through the C. elegans homologue of the elevenin neuropeptide SNET-1 ( Figure 4A). 119,120 Social context also affects learning in the honeybee A. mellifera.…”

Feeding state functionally reconfigures a sensory circuit to drive thermosensory behavioral plasticity

“…The odr-2b(3a) promoter was used to drive FLP expression primarily in AIB and AIZ (plasmid pWY046) ( Chou et al, 2001 ; Li et al, 2014 ). To generate pWY016, FRT::STOP::FRT sequences were amplified from sequences in the ser-2(2) p ::FRT::YFP plasmid (gift from Shawn Xu), and inserted into a vector containing GCaMP6s sequences ( Wu et al, 2019 ) by Gibson assembly (New England BioLabs). ser-2(2) p (4.7 kb) sequences were amplified from plasmids derived from ser-2(2) p ::FRT::YFP , and subsequently cloned upstream of FRT::STOP::FRT::GCaMP6s using Gateway (Thermo Fisher Scientific).…”

Feeding state functionally reconfigures a sensory circuit to drive thermosensory behavioral plasticity

“…Plasmids were generated using Gibson assembly (New England BioLabs) or In-Fusion cloning (Takara Bio) unless noted otherwise. To generate WY016, FRT::STOP::FRT sequences were amplified from sequences in the ser-2(2)p::FRT::YFP plasmid (gift from Shawn Xu), and inserted into a vector containing GCaMP6s sequences (Wu et al, 2019) by Gibson assembly (New England BioLabs). ser-2(2)p (4.7 kb) sequences were amplified from plasmids derived from ser-2(2)p::FRT::YFP, and cloned upstream of FRT::STOP::FRT::GCaMP6s to generate WY016 using Gateway (Thermo Fisher Scientific).…”