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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. Animals are constantly adjusting their behavior to respond to changes in the environment or to their internal state. This behavior modulation is achieved by altering the activity of neurons and circuits through a variety of neuroplasticity mechanisms. Chemical synapses are known to impact neuroplasticity in several different ways, but the diversity of mechanisms by which electrical synapses contribute is still being investigated. Electrical synapses are specialized sites of connection between neurons where ions and small signaling molecules can pass directly from one cell to the next. By passing small molecules through electrical synapses, neurons may be able to modify the activity of their neighbors. In this study we identify two genes that contribute to electrical synapses between two sensory neurons in C. elegans. We show that these electrical synapses are crucial for proper modulation of sensory responses, as without them animals are overly responsive to an aversive stimulus. In addition to pinpointing their sites of action, we present evidence that they may be contributing to neuromodulation by facilitating passage of the small molecule cGMP between neurons. Our work provides evidence for a role of electrical synapses in regulating animal behavior. [ABSTRACT FROM AUTHOR]

All animals rely on their ability to sense and respond to their environment to survive. However, the suitability of a behavioral response is context-dependent, and must reflect both an animal’s life history and its present internal state. Based on the integration of these variables, an animal’s needs can be prioritized to optimize survival strategies. Nociceptive sensory systems detect harmful stimuli and allow for the initiation of protective behavioral responses. The polymodal ASH sensory neurons are the primary nociceptors in C. elegans. We show here that the guanylyl cyclase ODR-1 functions non-cell-autonomously to downregulate ASH-mediated aversive behaviors and that ectopic cGMP generation in ASH is sufficient to dampen ASH sensitivity. We define a gap junction neural network that regulates nociception and propose that decentralized regulation of ASH signaling can allow for rapid correlation between an animal’s internal state and its behavioral output, lending modulatory flexibility to this hard-wired nociceptive neural circuit. [ABSTRACT FROM AUTHOR]

Summary: Signal transduction through heterotrimeric G proteins is critical for sensory response across species. Regulator of G protein signaling (RGS) proteins are negative regulators of signal transduction. Herein we describe a role for C. elegans RGS-3 in the regulation of sensory behaviors. rgs-3 mutant animals fail to respond to intense sensory stimuli but respond normally to low concentrations of specific odorants. We find that loss of RGS-3 leads to aberrantly increased G protein-coupled calcium signaling but decreased synaptic output, ultimately leading to behavioral defects. Thus, rgs-3 responses are restored by decreasing G protein-coupled signal transduction, either genetically or by exogenous dopamine, by expressing a calcium-binding protein to buffer calcium levels in sensory neurons or by enhancing glutamatergic synaptic transmission from sensory neurons. Therefore, while RGS proteins generally act to downregulate signaling, loss of a specific RGS protein in sensory neurons can lead to defective responses to external stimuli. [Copyright &y& Elsevier]

The effect of the detailed connectivity of a neural circuit on its function and the resulting behavior of the organism is a key question in many neural systems. Here, we study the circuit for nociception in C. elegans , which is composed of the same neurons in the two sexes that are wired differently. We show that the nociceptive sensory neurons respond similarly in the two sexes, yet the animals display sexually dimorphic behaviors to the same aversive stimuli. To uncover the role of the downstream network topology in shaping behavior, we learn and simulate network models that replicate the observed dimorphic behaviors and use them to predict simple network rewirings that would switch behavior between the sexes. We then show experimentally that these subtle synaptic rewirings indeed flip behavior. Interestingly, when presented with aversive cues, rewired males were compromised in finding mating partners, suggesting that network topologies that enable efficient avoidance of noxious cues have a reproductive "cost." Our results present a deconstruction of the design of a neural circuit that controls sexual behavior and how to reprogram it. [Display omitted] • C. elegans exhibits sexually dimorphic responses to nociceptive stimuli • Computational models show that circuit topology accounts for the dimorphic behavior • Model-based rewiring of single neurons or synapses flips sex-specific behavior • Rewired males are compromised in finding mates when presented with aversive cues Pechuk et al. study the circuit for nociceptive sensing and processing in hermaphrodite and male C. elegans. Combining circuit models and experimental characterization, they demonstrate that network topology shapes sexually dimorphic behavior. They show that simple rewiring reprograms behavior and demonstrates its sexual implications. [ABSTRACT FROM AUTHOR]