What a worm’s brain can teach us about sex differences in the nervous system
Ever wonder what goes on inside the brain of a worm? Northeastern University researchers have opened up that can of worms.
Ever wonder what goes on inside the brain of a worm — how they process information, respond to stimuli and perceive the world around them?
Northeastern University researchers have opened up that can of worms, specifically the one containing C. elegans, an incredibly tiny roundworm that’s one of the most extensively studied animals in biology.
A team of biophysicists has zoomed in on the brains of these one-millimeter-long creatures, specifically observing the two sexes. Hermaphrodite worms have exactly 302 neurons, distributed throughout the entirety of the worm’s nervous system. Roughly 200 of those neurons are located in the worm’s head, with the rest scattered along its body and tail, including throughout its reproductive organs. Males, on the other hand, have roughly 387.
Unlike many animals, female C. elegans are actually hermaphrodites, meaning they produce both eggs and sperm and can reproduce by fertilizing their own eggs.
The researchers were interested in observing the brain activity of male and hermaphrodite worms side by side as they interacted with a controlled environment, where researchers could deploy various stimuli, like odors from food and other chemical cues that indicate danger in their surroundings.
What they discovered is that those sexual differences, at the level of brain activity, run surprisingly deep. The findings could help scientists better understand how sex-specific differences in the nervous system influence behavior, reproduction and aging.
And the work could provide clues about how sex differences unfold across species.
Scientists use C. elegans as a model organism to investigate biological processes that also matter in humans, from fertility to aging. Research on the worms can help illuminate how errors in chromosome division contribute to miscarriages, infertility and birth defects, and how muscle-like contractions help move eggs through the reproductive system — a process that may offer insights into how muscles function in human organs, according to research conducted by Northeastern’s Cram Lab.
Because the worms typically live only about 20 days, they also offer a convenient way to investigate why organisms age and whether that process can be slowed.
“As someone who studies aging, I’m curious what this means for how males and hermaphrodites age,” said Javier Apfeld, an associate professor of biology at Northeastern University.
In a study published in Current Biology last month, the researchers detailed how nearly every sensory neuron in the two worms’ brains responded differently to at least one chemical cue. And even when two neurons reacted similarly to one particular odor, they could respond differently to another.
The two sexes’ brains diverged when presented with food, salt and pheromones in the pharyngeal nervous system, or the network of neurons involved in feeding and digestion, suggesting that sex differences extend beyond smell to the processing of chemical cues during feeding, the researchers wrote.
“They’re primarily chemosensory animals,” Vivek Venkatachalam, an associate professor of physics at Northeastern University’s College of Science, said of the worms, meaning they tend to experience the world predominantly through their olfactory and gustatory senses, or the chemical senses of smell and taste.
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Those sex differences — which scientists call “sexual dimorphism” — were so pronounced that it raises larger questions about how biological sex shapes the way nervous systems process information, and whether similar differences might be found in other animals, experts say.
It is the first “whole-brain comparison” of the neural activity between male and hermaphrodite worms, Venkatachalam said.
“One of the basic questions that we are asking — and there are many others as well — is how brain structure is related to brain function,” Venkatachalam told Northeastern Global News.
The animals are also transparent, so putting them under a microscope gives researchers an opportunity to see activity deep inside their brains.
The researchers were able to track the activity of individual neurons across the worms’ brains using a tool that detects changes in calcium levels inside neurons. Those changes show up as shifts in how brightly the neurons glow under the microscope. The calcium imaging technique is widely used to study neural circuits in worms, flies, mice and other experimental subjects.
Scientists were surprised by how widespread the differences were, and how much they depended on the specific chemical cue.
“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,” Apfeld said.
Venkatachalam cautioned that the findings in worms don’t necessarily translate directly to humans. But because many of the genes involved in nervous system function are shared across species, the research could offer a starting point for investigating how those genes influence brain activity in more complex animals.
“The goal is to learn principles of neuronal computation that are globally applicable,” he said.
