Dual Excitatory and Inhibitory Serotonergic Inputs Modulate Egg-laying in Caenorhabditis elegans

Serotonin (5-HT) regulates key processes in both vertebrates and invertebrates. Previously, four 5-HT receptors were identified in Caenorhabditis elegans that contributed to the 5-HT modulation of egg-laying. Therefore, to assess potential receptor interactions, we generated animals containing combinations of null alleles for each receptor, especially animals expressing only individual 5-HT receptors. 5-HT stimulated egg-laying and egg-retention correlated well with different combinations of predicted excitatory and inhibitory serotonergic inputs. For example, 5-HT did not stimulate egg-laying in ser-1, ser-7 or ser-7 ser-1 null animals and ser-7 ser-1 animals retained more eggs than wild-type animals. In contrast, 5-HT stimulated egg-laying in ser-4;mod-1 animals was greater than in wild-type animals and ser-4;mod-1 animals retained fewer eggs than wild-type animals. Surprisingly, ser-4;mod-1;ser-7 ser-1 animals retained the same number of eggs as wild-type animals and exhibited significant 5-HT stimulated egg-laying that was dependent on a previously uncharacterized receptor, SER-5. 5-HT stimulated egg-laying was absent in ser-5;ser-4;mod-1;ser-7 ser-1 animals and these animals retained more eggs than either wild-type or ser-4;mod-1;ser-7 ser-1 animals. The 5-HT sensitivity of egg-laying could be restored by ser-5 muscle expression. Together, these results highlight the dual excitatory/inhibitory serotonergic inputs that combine to modulate egg-laying.

Key Words: Caenorhabditis elegans, GPCR, behavior, egg-laying, serotonin

Online ISS 1091-6490
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