The Notch signaling pathway is conserved between species and plays important roles in cell fate determination during development of many tissue types, including the nervous system. Here we describe a non-developmental role for the C. elegans Notch homolog
lin-12 in the adult nervous system. C. elegans predominantly moves forward but intermittently initiates short spontaneous reversals.
lin-12 gain and loss of function mutant animals both had increased spontaneous reversal rates compared to wild type. Overexpressing
lin-12 and knocking down
lin-12 function by RNAi in otherwise wild type animals led to similar results. To rule out cell fate changes, we observed the cellular expression patterns of several reporter genes and saw no significant differences between
lin-12 and wild type animals in AVA, AVB, AVD, AVC, or AIY, interneurons important for locomotion and initiation of reversals. These results suggested that the behavioral defects we observed in
lin-12 mutants were not due to developmental changes in neurons. Instead, using a conditional, cold-sensitive gain of function
lin-12 allele, we found that increasing
lin-12 activity in adults ( i.e. , after nervous system development is complete) was sufficient to confer increased reversal rates. Cellular ablations, cell type specific expression experiments, and epistatic analysis suggested that both gain and loss of function
lin-12 activity in a subset of neurons (AVA, AVB, and AVG) was sufficient to confer increased reversals. Previous studies have implicated AMPA-class glutamate gated cation channels in regulating reversals. We therefore examined the role of the C. elegans AMPA receptor homolog
glr-1 . Reversals caused by
lin-12 gain or loss of function were strongly suppressed in a
glr-1 mutant background. We also observed nose touch defects in
lin-12 gain of function mutants that were consistent with defects in
glr-1 function. However, it is as yet unclear if
lin-12 regulates the function and/or expression of
glr-1 or other glutamate-gated ion channels. Our results demonstrate that
lin-12 Notch signaling regulates behavior and thus neuronal activity in the adult nervous system of C. elegans .