Lampreys have ‘fight or flight’ cells, challenging ideas about nervous system evolution

These sympathetic nervous system cells were thought to be lacking in jawless vertebrates


Even though lampreys look primitive, a new study found signs that their peripheral nervous system is more complex and more similar to that of humans than researchers previously thought.

T. Lawrence, Great Lakes Fishery Commission (CC BY-SA 2.0 DEED)

With terrifyingly sharp teeth arranged around a circular mouth, lampreys look about as primitive a vertebrate as you could imagine. But a new study finds that the animals have a surprising similarity to people: Lampreys have the nerve cells responsible for the “fight or flight” response. The finding challenges the idea that this part of the nervous system emerged later in evolutionary history, and it puts lampreys closer to complex vertebrates — like humans.

“The conclusions are textbook-changing level,” says Daniel Meulemans Medeiros, an evolutionary biologist at the University of Colorado Boulder who was not involved with the new study but has worked with the research group before. 

Sea lampreys (Petromyzon marinus) belong to a group of fish called jawless vertebrates, which scientists thought lacked nervous system characteristics seen in jawed vertebrates, such as the sympathetic nervous system. This system is what’s behind the “fight or flight” response, and it activates the body by releasing hormones to control body temperature and cardiovascular function.

In past work, Caltech neuroscientist Marianne Bronner had examined the lamprey nervous system in detail, specifically the peripheral nervous system, which lies outside of brain and spinal cord, and the neurons in the gut. While studying and developing markers for these neurons, Brittany Edens, a researcher in Bronner’s lab and coauthor of the new study, noticed peripheral neurons outside the lamprey’s intestine. Bronner’s team decided to investigate.

The team used a technique that tags and lights up specific mRNA in individual cells of lamprey embryos. That allowed the researchers to look at three or four genetic factors associated with sympathetic neurons simultaneously. A cluster of cells lining the heart and the trunk of the embryonic lampreys had these genetic factors, indicating that the cells were the sympathetic neurons seen in other vertebrates, the team reports April 17 in Nature.

Next, the team tracked where these cells originated by injecting a dye to label cells of the neural crest, a patch of stem cells that migrate during development and give rise to cells of the peripheral nervous system. The lamprey’s sympathetic neurons lit up with the dye, showing that the cells came from the neural crest, just like they do in more complex vertebrates.

But there were also key differences. Compared with other vertebrates, the lamprey’s sympathetic nervous system formed much later in development and the clusters of cells were smaller. Previous studies may have missed these cells by looking for them at the wrong time during embryo development. So even though the sympathetic system is present, it’s rudimentary nonetheless, Bronner says. “It’s very simplified compared to what it would be in mammals.”

The findings suggest that the sympathetic nervous system was not an innovation of jawed vertebrates, but rather that the blueprint for it has been around since even before lampreys diverged from the main vertebrate line about half a billion years ago, says Shreyas Suryanarayana, a neuroscientist at Duke University who was not involved with the study.

“As you look deeper, it becomes clear that the basic building blocks of these complex systems present in humans are, in fact, very old,” Suryanarayana says. In more complex vertebrates, this system then diversified, expanded and grew larger, he says.

Previous studies had already begun to dismantle the idea of a simple nervous system in lampreys. For example, researchers had found that connections and proteins in specific brain areas of the lamprey resembled those seen in other vertebrates. More recently, scientists found that signaling involved in how the lamprey’s brain organizes itself also applied to all vertebrates.

Medeiros suggests that researchers should now look even further back in evolutionary time at invertebrates to see if they also have sympathetic neurons, which could explain how the vertebrate nervous system evolved.

“That’s really the one of the questions that has fascinated me for years: How did you go from invertebrates to vertebrates?” Bronner says. “I don’t have the answer, but I will keep trying to figure it out.”

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