Sex-specific topology of the nociceptive circuit shapes dimorphic behavior in C. elegans

Abstract

How sexually dimorphic behavior is encoded in the nervous system is poorly understood. Here, we characterize the dimorphic nociceptive behavior in C. elegans and study the underlying circuits, which are composed of the same neurons but are wired differently. We show that while sensory transduction is similar in the two sexes, the downstream network topology markedly shapes behavior. We fit a network model that replicates the observed dimorphic behavior in response to external stimuli, and use it to predict simple network rewirings that would switch the behavior between the sexes. We then show experimentally that these subtle synaptic rewirings indeed flip behavior. Strikingly, 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.

Sexually dimorphic architecture and function of a mechanosensory circuit in C. elegans

“…For example, hermaphrodites detect food-related olfactory cues better than males due to enhanced expression of the odorant receptor ODR-10 in the AWA neuron 1 . Conversely, in the anterior nociceptive circuit, sensory detection of aversive cues seems identical in the two sexes, but the downstream connectivity to interneurons is highly dimorphic 10 . These topographical differences drive sexually dimorphic behavioral responses to nociceptive cues.…”

“…The sexually dimorphic behavior in response to the pheromone ESP1, for example, was shown to be mediated through dimorphic processing in third-and fourth-order brain areas 7,8 . Integration downstream to the sensory level is also evident in aggressive behavior in Drosophila and nociceptive behavior in C. elegans, where sexually dimorphic processing by downstream interneurons regulates the dimorphic behavior 9,10 . These examples demonstrate that for different types of sensory modalities, be it olfactory, auditory or chemo-aversion, sex differences can originate from dimorphism in distinct neuronal layers.The perception of mechanical forces, or mechanosensation, includes the perception of touch, hearing, proprioception and pain, all of which involve the transduction of mechanical forces into a cellular signal 11 .…”

Sexually dimorphic architecture and function of a mechanosensory circuit in C. elegans

“…For example, hermaphrodites detect food-related olfactory cues better than males due to enhanced expression of the odorant receptor ODR-10 in the AWA neuron 1 . Conversely, in the anterior nociceptive circuit, sensory detection of aversive cues seems identical in the two sexes, but the downstream connectivity to interneurons is highly dimorphic 10 . These topographical differences drive sexually dimorphic behavioral responses to nociceptive cues.…”

“…The sexually dimorphic behavior in response to the pheromone ESP1, for example, was shown to be mediated through dimorphic processing in third-and fourth-order brain areas 7,8 . Integration downstream to the sensory level is also evident in aggressive behavior in Drosophila and nociceptive behavior in C. elegans, where sexually dimorphic processing by downstream interneurons regulates the dimorphic behavior 9,10 . These examples demonstrate that for different types of sensory modalities, be it olfactory, auditory or chemo-aversion, sex differences can originate from dimorphism in distinct neuronal layers.…”

Sex-Specific Developmental Gene Expression Atlas Unveils Dimorphic Gene Networks inC. elegans

“…To gain insight into the molecular and genetic mechanisms underlying the sexual component of nervous system development, we asked how sexual identity, neuronal identity, and developmental stage intersect to drive gene expression in a model organism. We addressed this question using the nematode Caenorhabditis elegans, due to the detailed anatomical and molecular understanding of the nervous system of both sexes and the extensive sexual dimorphism they exhibit 18,19 at the resolution of single identifiable neurons, connections, and behaviors 2,[20][21][22] . As most sexual differences arise late in development, C. elegans offers a unique opportunity to track how sexspecific characteristics emerge during neuronal development.…”