When Nervous Systems Are Pushed to Their Limits

Wolfgang Stein is studying how nervous systems adapt to change in an unlikely spot: the stomach of a crab.

As oceans warm and extreme heat events become more common, neuroscientists like Stein are pushing their field in a new direction: testing how close to the edge a nervous system can operate before it fails and what helps it recover.

Stein, a neuroscientist at Illinois State University (ISU), studies the crab stomatogastric ganglion, the precise bundle of 26 neurons that regulates crustacean digestion. These neurons fire rhythmically, which in turn spurs regular contractions of the crab’s stomach, helping them break down and digest their food.

As a postdoctoral fellow at the University of Pennsylvania, Stein studied how nervous system messengers known as neuromodulators affected the stomatogastric system, isolating the ganglion from live animals and recording from it in the laboratory. Those recordings had to happen under precisely controlled conditions, he said.

“We were always told to keep the nervous systems at a precise temperature; otherwise, bad things happen,” Stein said. “At some point, I noticed that the effects of temperature on this system were actually much more dramatic than the effects of neuromodulators. And that made no sense to me, because this animal lives in the wild and experiences temperature changes over the seasons and sometimes daily.”

His interest was piqued. How did temperature affect this neural system, and what did that say about how the animals experience their natural environs? Can we learn something about how a warming world will affect animals’ nervous systems by understanding how the crab’s digestive neural circuit responds to temperature changes?

Today, Stein’s Crab Lab at ISU is working to answer those questions, aided with support from a Kavli Exploration Award in Neurobiology and Changing Ecosystems from The Kavli Foundation. The award sits within a larger philanthropic effort, by Kavli and others, to connect neuroscience with ecology and environmental science.

A new kind of neuroscience for a changing planet
Stein’s work on these 26 stomatogastric neurons is part of the larger, emerging field that sits at the intersection between neuroscience and environmental change. Studying how our brains and the nervous systems of diverse animal species respond to environmental changes, especially extreme perturbations, will be key to understanding the true impacts of a changing planet — and maybe even how to increase nervous systems’ resilience to some of the most dangerous environmental shifts.

“We learn a lot about the adaptability of these nervous systems when we look at how they respond to their natural environments,” Stein said. “And this will also influence our knowledge about human brains, because climate change affects us too.”

Although our brains aren’t the only aspects of our physiology that are affected by changing ecosystems, they’re key to understanding the impacts of climate change because much of animal behavior is effected through nervous systems, said Matthew Lovett-Barron, a neuroscientist at the University of California San Diego who studies neural activity and behavior in fish. And understanding how neural systems influence animals’ resilience or vulnerability to environmental change, as Stein is trying to do, is especially important, he said.

“From a practical standpoint, we want to understand if animals are going to be able to adapt to the types of changes we’re going to see in terrestrial and aquatic environments,” Lovett-Barron said. “It’s also interesting from a basic science standpoint to understand how much flexibility is inherent to nervous systems. This is something Wolfgang and others have been able to look at: What is the tolerance of these systems? What is their breaking point? And what are the mechanisms that allow for that tolerance or breaking?”

As a scientist, it’s been an exciting challenge to work at the crossroads of neuroscience and ecology, Stein said. His molecular neuroscience colleagues speak in a language of genes and proteins. His ecology colleagues talk about large-scale climate models.

“We’re trying to get at the mechanisms that connect the two fields. It’s an interesting place to be,” Stein said. “Frankly, I think as a society we need this, if we want to understand the impact of environmental change on nervous systems.”

“We’re kind of stuck in the middle between two major disciplines, trying to connect these bigger ideas,” said Mackenzie Seymour, a doctoral student working in Stein’s lab. “We’re really hypothesis-driven, where much of the ecology side tends to be more observation-driven.”

A crab in hot water
To study how ocean temperatures — and specifically extreme ocean heat waves that are becoming more common as the planet warms — might affect the nervous system, Stein and his laboratory team looked at the stomatogastric ganglion of five different crab species. Crabs, like most other aquatic animals (other than mammals), are poikilothermic, or essentially cold-blooded. That means their body temperature varies depending on the temperature of their surroundings, and they cannot regulate their internal temperatures the way mammals can. Aquatic animals are even more vulnerable to heat waves than terrestrial dwellers, because heat transfer is much greater in the water than in the air.

Temperature affects how ions move through cells, affecting neurons’ electrical activity. Depending on the system, higher temperatures could either lead to overexcitability or excess inhibition in neural circuits. But crabs — and many other aquatic animals — live in variable climates with natural swings in temperature. Stein wants to understand how their nervous systems adapt to that variability — and what is the breaking point at which that adaptation fails.

Crabs are an especially interesting animal to study in this context, because many crab species are invasive, meaning they are very good at adapting to new environments. And the 26 neurons of the stomatogastric ganglion are identical across many crustacean species, even those separated by hundreds of millions of years of evolution.

Stein and his lab team are studying this system in five different crab species from a range of habitats. Two of these, the Atlantic Jonah crab and the Pacific Northwest Dungeness crab, live in cold ocean climates with relatively little temperature fluctuations. Two others, the green crab and the Asian shore crab, live in tidepools and are adapted to a wide range of ocean temperatures. These two species are also highly invasive. The fifth species, the blue crab, lives in a warm but variable climate.

“These species have behaviors and habitats that differ in terms of climate change,” Stein said. “We actually have a natural experiment going on in the ocean, in addition to the experiments that we do in the lab.”

The scientists dissect out the intact stomatogastric ganglion, whose neurons are very large and easy to find under a microscope, and study its activity through electrical recordings in the lab. They look at how the systems’ rhythmic firings change depending on the temperature of the fluid in the petri dish. As other scientists have seen in the past, they found that the steady rhythm “crashes out” and stops firing rhythmically at high temperatures. Stein and his lab team found that, as they hypothesized, the three variable-habitat crab species have a much higher “crash” threshold than the two cold-water species. The variable-habitat species maintained rhythmic firing up to around 30 degrees Celsius, or 86 degrees Fahrenheit, while the Jonah and Dungeness crabs crashed out at around 25 degrees Celsius.

The mechanism of acclimation
They also found that they could acclimate green crabs, which live in variable climates, to warmer temperatures in the lab. Acclimating to warmer water raised the crabs’ crash temperature by a few degrees. But this acclimation takes at least a few weeks, raising the question as to whether even these more resilient species could easily adapt to rapid heat waves.

The team has also found a neuropeptide called CabTRP Ia that underlies the robustness of the stomatogastric system. When they apply that peptide to the ganglion of Jonah crabs in the lab, the cells can maintain their rhythmic firing to a higher temperature before crashing. The researchers are now looking at how different ion channels in the neurons affect their ability to withstand higher temperatures.

They’re also interested in looking at rhythmic neural systems in other animals, such as the circuits that regulate the heartbeat or breathing. Studying neural rhythms and their adaptation in model animals such as fruit flies or zebrafish will allow them to perform more genetic manipulations and answer more mechanistic questions than is currently possible in crabs. Stein’s collaborator and fellow Kavli Exploration Awardee Steffen Harzsch at the University of Greifswald in Germany is studying the stomatogastric ganglion system and the effects of environmental change in developing crabs. Their projects let them compare how the same neural circuit responds to stress in different crab species and at different life stages. Ultimately, they hope to find mechanisms of neural resilience to climate variability that apply across species.

“I hope that there are some common mechanisms that are shared by all animals that we can identify. That would be a great scientific breakthrough,” Stein said.

Uncovering that mechanism could eventually lead to new ways to protect against the harms of climate change, said Charlotte Steiger, a master’s student working in Stein’s lab.

“If you understand the mechanism that causes this to happen, it might allow you to mitigate the problem in the future,” Steiger said. “If we know what causes these effects, could that help us prevent the extinction of some species?”

As more research coalesces around these questions, what once looked like a niche curiosity is starting to resemble a new scientific community, built for a rapidly changing planet.