With 302 neurons, 200 of them in their heads, hermaphrodite female roundworms reveal surprising sex-specific differences in the nervous system and how these differences influence behavior, reproduction, and aging.
Researchers at Northeastern University compared brain activity in male and hermaphroditic Caenorhabditis elegans, a microscopic worm widely used in biological research to understand how sex wires males and female nervous systems differently.
Their study, published in Current Biology, showed that nearly every chemosensory neuron in a tiny roundworm responds differently to at least one chemical signal depending on the animal’s sex, “indicating that sexually dimorphic circuits are pervasive and stimulus-dependent,” the researchers wrote in the study.
As male and hermaphroditic nervous systems revealed widespread differences in how they process information, the lead researcher told Northeastern that their central question concerned how brain structure relates to brain function.
Mapping sex differences across the brain
At 1 millimeter long, transparent hermaphrodites Caenorhabditis elegans have 302 neurons throughout their nervous systems, while males have approximately 387, according to Northeastern University.
Vivek Venkatachalam, an associate professor of physics at Northeastern University, explained that the worms are primarily chemosensory animals. They rely heavily on smell and taste. Researchers monitored individual neurons as worms encountered chemical stimuli, including odors, salt, and pheromones. Using calcium imaging, a technique that measures changes in calcium levels inside neurons, they tracked changes in neural activity across the animals’ heads.
The team found that sensory responses varied between sexes and also depending on the stimulus.
“We’ve known for a while that the male and hermaphrodite worm nervous systems are wired somewhat differently, but a wiring diagram only tells you so much about how a brain actually works,” said Javier Apfeld, a Northeastern associate professor of biology, said in the Northeastern report.
The team found that sensory responses varied not only by sex but also by stimulus, identifying sex-specific responses in neurons associated with feeding and digestion.
“This dimorphic and monomorphic activity was present to a lesser extent in downstream interneurons and even less so in motoneurons, implicating sensory neurons as the primary source and location of sexually dimorphic activity,” the researchers reported.
The researchers also investigated whether differences in neural activity corresponded to differences in the physical connections between neurons.
Scientists compared the worms’ observed neural activity with previously published maps of synaptic connections, or connectomes. The researchers found that functional differences in neurons were distinct from differences in their physical connections.
In other words, researchers investigated whether neural activity corresponded to the physical connections between neurons. They found that structural differences did not predict functional changes.
“Comparing the functional activity we measured to the published synaptic connectomes of both sexes revealed that sexual dimorphism in functional connectivity was distinct from and complementary to sexual dimorphism in synaptic connectivity,” the study stated.
The findings could provide a foundation for investigating sex differences in nervous systems across other species. However, Venkatachalam cautioned that results from worms cannot necessarily be applied directly to humans.
“The goal is to learn principles of neuronal computation that are globally applicable,” he concluded to Northeastern news.