Notch signaling plays important roles in cell fate determination during development. We find that the C. elegans Notch homolog
lin-12 also functions to regulate behavior. C. elegans predominantly moves forward, but initiates short spontaneous reversals. Both gain and loss of
lin-12 function alleles caused increased reversal rates. Overexpressing
lin-12 (lin-12OE) or
lin-12(RNAi) led to similar changes confirming a role for
lin-12 in this behavior. To rule out a developmental role for
lin-12, we temporally increased or decreased
lin-12 activity, and found that reversal rate increases were induced within hours in young adult animals. Thus, altered behavior in
lin-12 animals is not due to developmental defects, but rather physiological changes in adult animals. Although
lin-12 expression has been previously detected in the vulval and somatic gonad lineages, reversal rates in wild type, lin-12OE, and
lin-12(RNAi) animals were unchanged when these tissues were eliminated. In contrast, expression of activated
lin-12 or RNAi knockdown of
lin-12 using the neuron-specific
glr-1 promoter reproduced reversal rate increases. No changes in the morphology of neurons known to control reversal rates were observed in
lin-12 animals.
lin-12 expression was observed in ventral cord neurons and the RIG neurons. The function of RIG neurons is unclear, but they gap junction to the AVB command interneurons that regulate locomotion. Ablation of RIG ameliorated the reversal rate increases of lin-12OE animals, but had no effect in control or
lin-12(RNAi) animals, suggesting that
lin-12 gain of function may act in the RIG neurons, but that
lin-12 loss of function may act in other neurons.
glr-1 encodes a glutamate receptor required for nose touch response that is expressed in command interneurons, RIG neurons and 12 other neurons. Although
glr-1 loss of function has no overt effect on reversal rates,
glr-1;
lin-12 animals had dramatically decreased reversal rates. We also observed nose touch response defects in animals with increased
lin-12 function, consistent with alterations in glutamatergic signaling. Notch has recently been implicated in learning paradigms in Drosophila and mice; we are interested in identifying neuronal downstream effectors of
lin-12 to address a conserved role for Notch signaling in adult neurons.