INX-18 and INX-19 play distinct roles in electrical synapses that modulate aversive behavior in Caenorhabditis elegans


Autoři: Lisa Voelker aff001;  Bishal Upadhyaya aff001;  Denise M. Ferkey aff003;  Sarah Woldemariam aff004;  Noelle D. L’Etoile aff004;  Ithai Rabinowitch aff001;  Jihong Bai aff001
Působiště autorů: Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America aff001;  Molecular and Cellular Biology Program, University of Washington, Seattle, WA, United States of America aff002;  Department of Biological Sciences, University at Buffalo, The State University of New York, Buffalo, NY, United States of America aff003;  Department of Cell and Tissue Biology, University of California, San Francisco, CA, United States of America aff004;  Department of Medical Neurobiology, Faculty of Medicine Hebrew, University of Jerusalem, Jerusalem, Israel aff005
Vyšlo v časopise: INX-18 and INX-19 play distinct roles in electrical synapses that modulate aversive behavior in Caenorhabditis elegans. PLoS Genet 15(10): e32767. doi:10.1371/journal.pgen.1008341
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008341

Souhrn

In order to respond to changing environments and fluctuations in internal states, animals adjust their behavior through diverse neuromodulatory mechanisms. In this study we show that electrical synapses between the ASH primary quinine-detecting sensory neurons and the neighboring ASK neurons are required for modulating the aversive response to the bitter tastant quinine in C. elegans. Mutant worms that lack the electrical synapse proteins INX-18 and INX-19 become hypersensitive to dilute quinine. Cell-specific rescue experiments indicate that inx-18 operates in ASK while inx-19 is required in both ASK and ASH for proper quinine sensitivity. Imaging analyses find that INX-19 in ASK and ASH localizes to the same regions in the nerve ring, suggesting that both sides of ASK-ASH electrical synapses contain INX-19. While inx-18 and inx-19 mutant animals have a similar behavioral phenotype, several lines of evidence suggest the proteins encoded by these genes play different roles in modulating the aversive quinine response. First, INX-18 and INX-19 localize to different regions of the nerve ring, indicating that they are not present in the same synapses. Second, removing inx-18 disrupts the distribution of INX-19, while removing inx-19 does not alter INX-18 localization. Finally, by using a fluorescent cGMP reporter, we find that INX-18 and INX-19 have distinct roles in establishing cGMP levels in ASK and ASH. Together, these results demonstrate that electrical synapses containing INX-18 and INX-19 facilitate modulation of ASH nociceptive signaling. Our findings support the idea that a network of electrical synapses mediates cGMP exchange between neurons, enabling modulation of sensory responses and behavior.

Klíčová slova:

Animal behavior – Axons – Caenorhabditis elegans – Neurons – Quinine – Synapses – Electrical synapses – cGMP signaling


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Genetika Reprodukční medicína

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