In a new study published in Cell Reports, (PDF) researchers from the labs of MCB’s Florian Engert and Mark Fishman of the Department of Stem Cell and Regenerative Biology use larval zebrafish to probe a longstanding question in biology and psychology: Do changes in the body drive emotional states—or are body and behavior coordinated in parallel by the brain?
The work, led by co-advised postdoctoral fellow Kristian Herrera, focuses on interoception—the brain’s ability to sense internal physiological signals such as heart rate—and how those signals relate to shifts in behavior.
“The goal of this project was to try to figure out what role interoception might be playing in setting emotional or behavioral states,” Herrera explains.
Scaring Fish, Watching Hearts
The team studied larval zebrafish performing a well-characterized visuomotor task, the optomotor response (OMR), in which fish swim to follow moving visual patterns. When threatened, however, fish suppress this behavior and instead “freeze,” a defensive state accompanied by a rise in heart rate that could last for minutes.
“When we scare the fish, it ignores stimuli that would normally make it swim, and just kind of hangs out,” Herrera said. “At the same time, the heart rate goes up.”
The synchronization was striking. “The higher the heart rate, the less the animal was responding to these motion stimuli,” he noted.
Previous work in mice had suggested that artificially increasing heart rate using optogenetics—a light-based genetic tool to control cells—could induce anxiety-like behavior. That raised the possibility that the racing heart itself might drive behavioral changes.
Herrera and colleagues wanted to know: In a natural threat response, is the elevated heart rate actually causing the behavioral suppression?
Separating Heart from Behavior
To disentangle the two, the researchers searched for ways to break the tight coupling between cardiac and behavioral changes. Most manipulations affected both together. But when they severed sympathetic input to the heart—the nerves that release norepinephrine to increase heart rate—the picture changed.
“If you get rid of the nerves that upregulate heart rate, the heart rate doesn’t change after you scare the fish—but the behavior still does,” Herrera said.
In other words, the fish still suppressed swimming in response to threat, even without the tachycardia.
“That means that in the natural situation, you have a kind of top-down coordination from the brain,” he explained. “The brain is, at the same time, telling the heart rate to go up and independently telling the behavior to change.”
The findings challenge a strong interpretation of the classic James-Lange theory, proposed by William James in the 19th century, which suggested that emotions arise from sensing bodily changes—such as feeling afraid because your heart is pounding.
“This kind of puts a bit of a damper on that particular model, at least in this developmental stage of the fish,” Herrera said.
When Artificial Manipulation Tells a Different Story
The team then recreated the mouse-style experiment in zebrafish. They expressed a light-sensitive ion channel in the heart, allowing them to precisely control heart rate with flashes of light.
Artificially increasing the heart rate suppressed the OMR behavior. But the mechanism turned out to be very different from the natural threat response.
Optogenetic pacing interfered with the heart’s normal filling phase, reducing stroke volume and limiting oxygen delivery to the brain. When the researchers supplemented the water with extra oxygen, the behavioral suppression disappeared.
“That artificial change in heart rate was pretty different from what happens naturally,” Herrera said.
Neural imaging reinforced this conclusion. The brain regions activated during threat-induced tachycardia differed from those engaged during optogenetic pacing. Notably, the artificial manipulation did not activate neurons normally involved in sensing internal bodily states.
The result underscores a cautionary message for neuroscience. “Optogenetic manipulations need to be very carefully assessed,” Herrera said. “They can have all sorts of off-target effects.”
An Ancestral System, A Powerful Model
Beyond clarifying the role of cardiac feedback, the study highlights the zebrafish as a powerful model for studying how body and brain states are integrated.
“The fish is working very hard to coordinate its body with changes in behavior,” Herrera said. “It’s trying to make sure the heart is changing in a way that’s synchronized with how much energy it’s putting out.”
Because the autonomic nervous system is evolutionarily ancient, insights from zebrafish may extend broadly across vertebrates. The ability to image heart dynamics, brain activity, and behavior simultaneously—and manipulate each optically—offers a uniquely comprehensive view.
Ultimately, the findings suggest that during natural threat responses, the brain orchestrates heart and behavior in parallel rather than relying on cardiac feedback as a master regulator of emotion.
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