The Insulin/PI 3-Kinase Pathway Regulates Salt Chemotaxis Learning in Caenorhabditis elegans

Abstract

The insulin-like signaling pathway is known to regulate fat metabolism, dauer formation, and longevity in Caenorhabditis elegans. Here, we report that this pathway is also involved in salt chemotaxis learning, in which animals previously exposed to a chemoattractive salt under starvation conditions start to show salt avoidance behavior. Mutants of ins-1, daf-2, age-1, pdk-1, and akt-1, which encode the homologs of insulin, insulin/IGF-I receptor, PI 3-kinase, phosphoinositide-dependent kinase, and Akt/PKB, respectively, show severe defects in salt chemotaxis learning. daf-2 and age-1 act in the ASER salt-sensing neuron, and the activity level of the DAF-2/AGE-1 pathway in this neuron determines the extent and orientation of salt chemotaxis. On the other hand, ins-1 acts in AIA interneurons, which receive direct synaptic inputs from sensory neurons and also send synaptic outputs to ASER. These results suggest that INS-1 secreted from AIA interneurons provides feedback to ASER to generate plasticity of chemotaxis.

Generation and modulation of chemosensory behaviors in C. elegans

“…A subset of molecules implicated in mediating neuronal circuit plasticity are shown. See text for references and hence ASER functions [170]. These findings on the role of insulin in regulating neuronal functions provides the opportunity to define how internal metabolic state may modulate chemosensory neuron functions.…”

“…Two interesting pathways have been implicated in these associative behavioral paradigms. Both hen-1 mutants and mutants in the insulin signaling pathway, including animals mutant for the daf-2 insulin receptor, show a compromised ability to avoid an attractive salt stimulus when paired with the aversive stimulus of starvation (salt chemotaxis learning) [169,170]. Mutations in these genes do not affect responses to salt in the absence of conditioning.…”

“…3b). The DAF-2 insulin receptor and its effector PI3 kinase have been shown to act only in the ASER neurons to mediate salt chemotaxis learning, possibly via regulation of ASER synaptic output [170] (Fig. 3b).…”

“…3b). The ligand for DAF-2 in this pathway is likely INS-1, which is produced by the AIA postsynaptic interneurons [170]. Thus, a provocative model for salt chemotaxis learning is that upon conditioning, insulin is produced by the AIA interneurons, which in turn feeds back onto the ASER chemosensory neurons to regulate ASER synaptic output, Fig.…”

Insulin-like signaling pathway functions in integrative response to an olfactory and a gustatory stimuli in Caenorhabditis elegans

“…Components of the insulin-like signaling pathway are required for sensory integration learning in C. elegans Several learning paradigms in C. elegans, such as salt chemotaxis learning (Saeki et al, 2001;Tomioka et al, 2006), olfactory adaptation (Colbert and Bargmann, 1995), and temperature learning (Mohri et al, 2005) have been utilized to investigate associative learning and memory. The components of the insulin-like signaling pathway in C. elegans are highly conserved with those in mammals, the mammalian orthologs in C. elegans including DAF-2, a homolog of the insulin receptor; AGE-1, a PI 3-kinase homolog; DAF-18, a PTEN (phosphatase and tensin homolog deleted on chromosome 10) lipid phosphatase homolog; PDK-1, AKT-1/2 and SGK-1, homologs of phosphoinositide-dependent protein kinases; and DAF-16, a FOXO family transcription factor (Fig.…”