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. 2018 Mar 19;9:1128. doi: 10.1038/s41467-018-03333-6

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© The Author(s) 2018

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 4 — Sertraline attenuates C. elegans responses to the P. pacificus predator. a Sertraline attenuates C. elegans respnses to predator cue and fructose, whereas copper avoidance is only slightly reduced. b The effect of sertraline is lost in tax-4 and ocr-2 mutants, and modulation is restored when TAX-4 is restored to either ASI or ASJ, or when OCR-2 is restored to ASH or ADL. c Sertraline requires GABA, but not glutamate signaling. Sertraline modulates avoidance responses of eat-4 (glutamate receptor), but not unc-25 (glutamic acid decarboxylase, required for GABA synthesis) mutants. Adding GABA exogenously to plates restores sertraline modulation to unc-25 mutants. d Defective unc-25 response is rescued by expressing wild-type unc-25 cDNA under the unc-25 promoter or a RIS-selective promoter. Knocking down unc-25 specifically in RIS interneuron partially blocks sertraline modulation of predator avoidance. e Sertraline attenuates mutants in multiple GABA transporters including unc-47, snf-11, snf-10, and unc-46 (a transmembrane protein that recruits UNC-47). f Animals were treated with predator cue or predator cue and sertraline for 30 min and egg-laying was monitored for 60 min after removal of these compounds. g C. elegans detects predator cue using sensory circuits consisting of ASI, ASJ, ASH, and ADL neurons that use CNG and TRP channels and act in a redundant manner to generate rapid avoidance. In contrast, CNG channels act in ASI and ASJ neurons to reduce egg laying over many minutes. Sertraline attenuates both predator-induced avoidance behavior and egg-laying behavior downstream of these sensory neurons. Averages of either n > 30 (a–e) or n > 35 (f) and s.e.m. are shown. *p < 0.05 compared to controls obtained using Fisher’s exact t-test with Bonferroni correction (a–e) and *p < 0.05 compared to controls obtained using a two-way ANOVA (f)