Antagonistic regulation of salt and sugar chemotaxis plasticity by a single chemosensory neuron in Caenorhabditis elegans.

The nematode Caenorhabditis elegans memorizes various external chemicals, such as ions and odorants, during feeding. Here we find that C. elegans is attracted to the monosaccharides glucose and fructose after exposure to these monosaccharides in the presence of food; however, it avoids them without conditioning. The attraction to glucose requires a gustatory neuron called ASEL. ASEL activity increases when glucose concentration decreases. Optogenetic ASEL stimulation promotes forward movements; however, after glucose conditioning, it promotes turning, suggesting that after glucose conditioning, the behavioral output of ASEL activation switches toward glucose. We previously reported that chemotaxis toward sodium ion (Na+), which is sensed by ASEL, increases after Na+ conditioning in the presence of food. Interestingly, glucose conditioning decreases Na+ chemotaxis, and conversely, Na+ conditioning decreases glucose chemotaxis, suggesting the reciprocal inhibition of learned chemotaxis to distinct chemicals. The activation of PKC-1, an nPKC ε/η ortholog, in ASEL promotes glucose chemotaxis and decreases Na+ chemotaxis after glucose conditioning. Furthermore, genetic screening identified ENSA-1, an ortholog of the protein phosphatase inhibitor ARPP-16/19, which functions in parallel with PKC-1 in glucose-induced chemotactic learning toward distinct chemicals. These findings suggest that kinase-phosphatase signaling regulates the balance between learned behaviors based on glucose conditioning in ASEL, which might contribute to migration toward chemical compositions where the animals were previously fed.

Involvement of HECT-type E3 ubiquitin ligase genes in salt chemotaxis learning in Caenorhabditis elegans.

The ubiquitin-proteasome system is associated with various phenomena including learning and memory. In this study, we report that E3 ubiquitin ligase homologs and proteasome function are involved in taste avoidance learning, a type of associative learning between starvation and salt concentrations, in Caenorhabditis elegans. Pharmacological inhibition of proteasome function using bortezomib causes severe defects in taste avoidance learning. Among 9 HECT-type ubiquitin ligase genes, loss-of-function mutations of 6 ubiquitin ligase genes cause significant abnormalities in taste avoidance learning. Double mutations of those genes cause lethality or enhanced defects in taste avoidance learning, suggesting that the HECT-type ubiquitin ligases act in multiple pathways in the processes of learning. Furthermore, mutations of the ubiquitin ligase genes cause additive effects on taste avoidance learning defects of the insulin-like signaling mutants. Our findings unveil the consequences of aberrant functions of the proteasome and ubiquitin systems in learning behavior of Caenorhabditis elegans.