elegans learning and memory ( Figure
1). Neuropeptides can function as direct or indirect modulators of synaptic output, as primary neuronal signaling molecules, or in a neuroendocrine fashion. Like small neurotransmitters, neuropeptides play key roles RG7420 research buy in a wide variety of processes, and their role in learning and memory is an emerging trend. It is predicted that the C. elegans genome has 119 neuropeptide precursor genes that are processed into over 250 peptides. These can be categorized into three groups: 1) the insulin-like peptides with 40 members; 2) the FMRFamide (Phe-Met-Arg-Phe-amide)-like peptide (flp) family with 31; and 3) the 48 general neuropeptide-like protein (nlp) genes whose only unifying characteristic is that they are this website unlike the previous two families [7•]. In addition to the receptor tyrosine kinase insulin/IGF receptors encoded by daf-2, there are an estimated
128 neuropeptide G protein-coupled receptors, the majority of which remain functionally uncharacterized and orphaned. By reviewing recent findings for the role of neuropeptides in learning and memory we hope to highlight the advantages of behavioral genetics research in C. elegans ( Table 1). Zhang et al.  demonstrated that C. elegans can learn to avoid odorants released by strains of pathogenic bacteria, and to prefer odors released by non-pathogenic strains. Serotonin released from the chemosensory neuron ADF acts on various interneurons to associate infection with specific bacteria . The target of the ADF serotonin signal HSP90 is the serotonin-gated chloride channel MOD-1 . Using known promoters to selectively express MOD-1 in specific neurons of MOD-1 defective mutants, Zhang
et al.  demonstrated that MOD-1 functions in several interneurons to modulate aversive learning. In a recent series of experiments, Chen et al. [9••] examined the potential role of insulin-like peptides (ILPs) in learned aversion to attractive pathogenic bacteria using strains with reduction of function alleles for the gene encoding the insulin/IGF-1 receptor, DAF-2. These mutants were defective in learning to avoid the smell of pathogenic bacteria [9••]. Learning was also disrupted by a semi-dominant mutation in ILP DAF-28 [9••]. DAF-28 has previously been shown to disrupt its own synthesis, as well as the synthesis of structurally related peptides expressed in the same cell . After ruling out a role for DAF-28, further mutant analysis implicated the ILPs INS-6 and INS-7 as influential paracrine mediators of learned aversion to pathogens [9••]. Specifically, a learning deficit caused by loss of ins-6 could be suppressed by loss of ins-7 [9••]. Neuron specific rescue studies revealed that INS-6 is released from ASI sensory neurons to repress transcription of learning-inhibitory INS-7 [9••]. In ins-6 mutants, URX-generated INS-7 disrupts learning via the DAF-2 receptor on the RIA interneurons of the learning circuit [9••].