Dissecting the Serotonergic Food Signal Stimulating Sensory-Mediated Aversive Behavior in C. elegans

Nutritional state often modulates olfaction and in Caenorhabditis elegans food stimulates aversive responses mediated by the nociceptive ASH sensory neurons. In the present study, we have characterized the role of key serotonergic neurons that differentially modulate aversive behavior in response to changing nutritional status. The serotonergic NSM and ADF neurons play antagonistic roles in food stimulation. NSM 5-HT activates SER-5 on the ASHs and SER-1 on the RIA interneurons and stimulates aversive responses, suggesting that food-dependent serotonergic stimulation involves local changes in 5-HT levels mediated by extrasynaptic 5-HT receptors. In contrast, ADF 5-HT activates SER-1 on the octopaminergic RIC interneurons to inhibit food–stimulation, suggesting neuron-specific stimulatory and inhibitory roles for SER-1 signaling. Both the NSMs and ADFs express INS-1, an insulin-like peptide, that appears to cell autonomously inhibit serotonergic signaling. Food also modulates directional decisions after reversal is complete, through the same serotonergic neurons and receptors involved in the initiation of reversal, and the decision to continue forward or change direction after reversal is dictated entirely by nutritional state. These results highlight the complexity of the “food signal” and serotonergic signaling in the modulation of sensory-mediated aversive behaviors

PAPP paralyzes <i>C</i>. <i>elegans</i> via SER-4 and DOP-3.

<p><b>A-C.</b> Paralysis of wild type, mutant and transgenic <i>C</i>. <i>elegans</i> on hypotonic non-NGM agar plates. <b>A.</b> PAPP (0.5 mM)-dependent paralysis of wild-type, 5-HT <i>quint</i> and 5-HT <i>quint</i> animals expressing SER-4 in the cholinergic motor neurons (P<i>unc-17β</i>). Data are presented as mean ± SE (n = 3). <b>B.</b> Dose-response curves for PAPP-dependent paralysis at 15 min exposure for wild type, 5-HT <i>quint</i> and 5-HT <i>quint</i> animals expressing SER-4 in the cholinergic motor neurons (P<i>unc-17β</i>). <b>C.</b> PAPP (0.5 mM)-dependent paralysis of 5-HT <i>quint</i> and 5-HT <i>quint</i> animals expressing P<i>dop-3</i>::<i>dop-3</i> RNAi. Data are presented as mean ± SE (n = 3). ‘*’ p≤0.001, significantly different from 5-HT <i>quint</i> animals assayed under identical conditions.</p

5-HT and 5-HT receptor agonists selectively paralyze <i>C</i>. <i>elegans</i> 5-HT receptor mutant animals expressing nematode, insect or human 5-HT₁-like receptors in the cholinergic motor neurons.

<p><b>A-C.</b> Paralysis of wild type, mutant and transgenic <i>C</i>. <i>elegans</i> on hypotonic, non-NGM agar plates. <b>A.</b> 5-HT (1 mM)-dependent paralysis of 5-HT <i>quint</i> animals expressing either <i>C</i>. <i>elegans</i> 5-HT₁-like (SER-4), <i>Drosophila</i> 5-HT₁-like, or human 5-HT_1A receptor in cholinergic motor neurons (P<i>unc-17β</i>). Data are presented as mean ± SE (n = 3). <b>B.</b> 8-OH-DPAT (2 mM)-dependent paralysis of 5-HT <i>quint</i> animals expressing either <i>C</i>. <i>elegans</i> 5-HT₁-like (SER-4), <i>Drosophila</i> 5-HT₁-like, or human 5-HT_1A receptor in cholinergic motor neurons (P<i>unc-17β</i>). Data are presented as mean ± SE (n = 3). <b>C.</b> Sumatriptan (1 mM)-dependent paralysis of wild type, 5-HT <i>quint</i> animals expressing either <i>C</i>. <i>elegans</i> 5-HT₁-like (SER-4), <i>Drosophila</i> 5-HT₁-like, or human 5-HT_1A receptor in cholinergic motor neurons (P<i>unc-17β</i>). Data are presented as mean ± SE (n = 3).</p