Sex differences in a Caenorhabditis elegans sensory behavior

Sex differences in the structure and function of the nervous system exist throughout the animal kingdom. Together with sex-biases in neurological diseases, this highlights the importance of studying how sexual differentiation modifies neural circuits and function. Taking advantage of the unique strengths of the nematode C. elegans, we explore how "neural sex", the sexual state of a given neuron established by cell-intrinsic sex determination, regulates the function of the "core" neural circuitry composed of neurons common to both sexes. To ask how neural sex influences behavior, we have examined olfaction, well-described in the C. elegans hermaphrodite but previously unstudied in the male. Using a novel assay involving the simultaneous presentation of two attractants, we have observed characteristic and distinct sex differences in olfactory preference behaviors. These sex differences were prominent before sexual maturation and did not require the gonad or germline, suggesting that core neural circuitry itself may be the cellular focus of sexually different shared behavior. To address this directly, we switched the sexual state of subsets of core neurons by cell-type specific expression of sexual regulators. We found that the neural sex of even a single sensory neuron, AWA, can determine the sexual phenotype of olfactory preference, indicating that AWA itself possesses sexually different functional properties. Moreover, at least some of these functional properties arise through sex differences in the expression of the odorant receptor ODR-10, providing a molecular mechanism for the generation of sexually different shared sensory function. This work has revealed a novel pathway for bringing about sex differences in the function of shared neural circuitry, and may shed light on the nature of sexual dimorphisms in the vertebrate nervous system.