Is There a Difference in Brain Structure Between Males and Females? Insights From a Single Neuron in C. elegans
The quest to understand whether the structural differences in male and female brains contribute to behavioral and neurological disparities has been a long-standing challenge in neuroscience. Human brains, with their approximately 75 billion neurons intricately interconnected, present an almost insurmountable complexity when attempting to isolate sex-specific differences at the cellular level. However, a groundbreaking study using the nematode Caenorhabditis elegans—a microscopic worm with a completely mapped nervous system—has revealed a fascinating example of sexual dimorphism in the structure of a single neuron, shedding light on how subtle cellular-level differences may influence behavior.
Caenorhabditis elegans has emerged as an exceptionally valuable model organism for neurobiological research due to its well-defined development and simple, invariant neural architecture. Unlike humans, C. elegans exists in two sexes: males and hermaphrodites. Hermaphrodites are unique in that they are self-fertilizing, capable of producing both sperm and eggs, thus bypassing the need for a partner in reproduction. This anatomical and reproductive simplicity provides an ideal system to explore how sex differences at the cellular level may affect neural function and behavior without the overwhelming complexity inherent to mammalian brains.
In recent research conducted at the Technion-Israel Institute of Technology, scientists focused on the sensory neuron PVD, renowned for its intricate and highly branched dendritic arborization resembling a candelabra, or menorah. While extensively studied in hermaphrodites, where PVD primarily facilitates nociceptive (pain) functions, the neuron’s anatomy and role in males had remained unexplored. This research endeavor sought to map PVD’s structural differences in males and evaluate whether these differences contribute to male-specific behaviors.
The findings revealed that, while the characteristic menorah-like dendritic structures of PVD remain consistent across both sexes, males exhibit additional branching patterns extending specifically into the tail fan—a specialized organ involved in mating. This male-specific neural architecture was not a remnant of developmental overlap but rather emerged during the terminal developmental molt from juvenile to adult stage. Such innovations underline the neuron’s secondary role in males, supplementing its sensory duties with functions directly tied to reproductive behavior.
These male-specific branches of PVD were discovered to be independent of previously characterized neurons inhabiting the tail fan region, indicating that PVD adopts a unique neural strategy to integrate mating-related information. Behavioral assays corroborated anatomical data; males with disrupted development of PVD’s extended branches exhibited slower, less coordinated mating behavior. This causative link between neuron structure and function highlights a rare and direct example of sexual dimorphism at the single-neuron level impacting organismal behavior.
Understanding sexual dimorphism in the nervous system holds broader implications, given that many human neuropsychiatric and neurodegenerative disorders present sex-biased prevalence. For instance, depression affects women more frequently, while Parkinson’s disease shows a higher incidence in men. However, in the context of the human brain, pinpointing the influence of single-neuron structural differences has been nearly impossible, obscured by the brain’s extreme complexity and plasticity.
C. elegans presents a remarkable contrast, possessing exactly 302 neurons in hermaphrodites and an anatomically distinct male nervous system with approximately 381 neurons due to additional sexually dimorphic cells. The invariance in neuron identity and precise connectomics has enabled researchers to evaluate morphology and connections with unparalleled resolution. This fidelity facilitates the investigation of questions regarding how neuronal identity, morphology, and connectivity differ between sexes and influence behavior.
The work led by Drs. Yael Iosilevskii and Menachem Katz, in collaboration with Prof. David H. Hall, focused keenly on the PVD neuron not only because of its elaborate branching but also due to the behavioral specificity it exhibited. Their study’s implications extend to understanding how neural circuits adapt during sexual maturation, and how the nervous system integrates modifications to produce behaviorally relevant outputs—from simple sensory perception to complex mating routines.
Moreover, this research illuminates the broader mechanisms by which sexually dimorphic behaviors can emerge from molecular and cellular modifications within a defined neural substrate. The timing of dendritic elaborations in males coinciding with sexual maturation suggests tightly regulated developmental programs that remodel neuronal arbors in response to genetic and hormonal cues intrinsic to sex determination.
The identification of male-specific neuronal branches in PVD also invites intriguing questions about the plasticity and adaptability of neurons generally considered to have fixed functions. The addition of branches related to reproductive behavior illustrates that even a traditionally sensory neuron can acquire multifunctionality, hinting at evolutionary pressures shaping neuronal circuitry to optimize fitness.
This discovery sets a precedent in neurobiology by linking single-neuron structural sexual dimorphisms directly to distinct behavioral phenotypes. It opens avenues for future research probing how widespread such neuron-level differences might be across other neural types and species, and how different neuronal morphologies translate to sex-specific functional outputs.
Given the transparent body and accessibility of C. elegans to genetic manipulation, this model will undoubtedly continue to offer unique insights into the cellular basis of behavioral dimorphism. The study’s findings could inspire analogous research in more complex organisms, eventually informing us on the neurobiological underpinnings of sex differences in humans and how these relate to susceptibility to neurological diseases.
In conclusion, the discovery that the PVD neuron in male C. elegans develops additional branching structures with a critical role in mating behavior represents a remarkable leap in understanding sexual dimorphism at the most elementary level of brain structure—a single neuron. Such insights reinforce the concept that even minuscule differences in neural architecture can yield profound behavioral consequences, emphasizing the intricate interplay between neuron morphology, sex, and function.
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Subject of Research: Animals
Article Title: The PVD neuron has male-specific structure and mating function in Caenorhabditis elegans
News Publication Date: 26-Mar-2025
Web References: http://dx.doi.org/10.1073/pnas.2421376122
Image Credits: Podbilewicz’s Lab, Technion
Keywords: Cell biology, Sexual dimorphism, Neuroscience, Neural development, C. elegans, Sensory neuron, Behavioral neuroscience
