With navigating nematodes, scientists map out how brains implement behaviors

Animal behavior reflects a complex interplay between an animal’s brain and its sensory surroundings. Only rarely have scientists been able to discern how actions emerge from this interaction. A new open-access study in Nature Neuroscience by researchers in The Picower Institute for Learning and Memory at MIT offers one example by revealing how circuits of neurons within C. elegans nematode worms respond to odors and generate movement as they pursue of smells they like and evade ones they don’t.“Across the animal kingdom, there are just so many remarkable behaviors,” says study senior author Steven Flavell, associate professor in the Picower Institute and MIT’s Department of Brain and Cognitive Sciences and an investigator of the Howard Hughes Medical Institute. “With modern neuroscience tools, we are finally gaining the ability to map their mechanistic underpinnings.”By the end of the study, which former graduate student Talya Kramer PhD ’25 led as her doctoral thesis research, the team was able to show exactly which neurons in the worm’s brain did which of the jobs needed to sense where smells were coming from, plan turns toward or away from them, shift to reverse (like old-fashioned radio-controlled cars, C. elegans worms turn in reverse), execute the turns, and then go back to moving forward. Not only did the study reveal the sequence and each neuron’s role in it, but it also demonstrated that worms are more skillful and intentional in these actions than perhaps they’ve received credit for. And finally, the study demonstrated that it’s all coordinated by the neuromodulatory chemical tyramine.“One thing that really excited us about this study is that we were able to see what a sensorimotor arc looks like at the scale of a whole nervous system: all the bits and pieces, from responses to the sensory cue until the behavioral response is implemented,” Flavell says.Seeing the sequenceTo do the research, Kramer put worms in dishes with spots of odors they’d either want to navigate toward or slither away from. With the lab’s custom microscopes and software, she and her co-authors could track how the worms navigated and all the electrical activity of more than 100 neurons in their brains during those behaviors (the worms only have 302 neurons total).The surveillance enabled Kramer, Flavell, and their colleagues to observe that the worms weren’t just ambling randomly until they happened to get where they’d want to be. Instead, the worms would execute turns with advantageous timing and at well-chosen angles. The worms seemed to know what they were doing as they navigated along the gradients of the odors.Inside their heads, patterns of electrical activity among a cohort of 10 neurons (indicated by flashing green light tied to the flux of calcium ions in the cells), revealed the sequence of neural activation that enabled the worms to execute these sensible sensory-guided motions: forward, then into reverse, then into the turn, and then back to forward. Particular neurons guided each of these steps, including detecting the odors, planning the turn, switching into reverse, and then executing the turns.A couple of neurons stood out as key gears in the sequence. A neuron called SAA proved pivotal for integrating odor detection with planning movement, as its activity predicted the direction of the eventual turn. Several neurons were flexible enough to show different activity patterns depending on factors such as where the odors were and whether the worm was moving forward or in reverse.And if the neurons are indeed turning and shifting gears, then the neuromodulator tyramine (the worm analog of norepinephrine) was the signal essential to switch their gears. After the worms started moving in reverse, tyramine from the neuron RIM enabled other neurons in the sequence to change their activity appropriately to execute the turns. In several experiments the scientists knocked out RIM tyramine and saw that the navigation behaviors and the sequence of neural activity largely fell apart.“The neuromodulator tyramine plays a central role in organizing these sequential brain activity patterns,” Flavell says.In addition to Flavell and Kramer, the paper’s other authors are Flossie Wan, Sara Pugliese, Adam Atanas, Sreeparna Pradhan, Alex Hiser, Lillie Godinez, Jinyue Luo, Eric Bueno, and Thomas Felt.A MathWorks Science Fellowship, the National Institutes of Health, the National Science Foundation, The McKnight Foundation, The Alfred P. Sloan Foundation, the Freedom Together Foundation, and HHMI provided funding to support the work.