Eve Marder

Eve Marder discovered early on that the easiest response to that most typical of adult questions—what do you want to be when you grow up—was “I want to be a scientist.” It seemed to satisfy and stymy adults simultaneously, allowing Marder to get back to what she was doing, which when she first contrived the answer, was reading a science book.

Marder was a well-rounded student who enjoyed and excelled at all subjects. She attended Brandeis University with an initial intention of becoming a civil rights lawyer. When a political science course proved uninteresting, Marder considered becoming an English major before ultimately choosing biology, reasoning she could go to graduate school in English with a biology degree, but she could not go to graduate school in biology with an English degree.

A junior year course on abnormal psychology—particularly an observation by her professor about schizophrenia and inhibition in the brain—sealed her future career. She was not only going to be a scientist, she was going to be a neuroscientist. “I kept reading neuroscience and turned all the papers I wrote for other biology courses into neuroscience topics.” It was the beginning of 45 years of posing fundamental questions about how the brain works.

And 45 years of uncovering answers to questions about the dynamics of neuronal networks.

Eve Marder studies how circuit function arises from the interactions between intrinsic properties of individual neurons and their synaptic connections. Her research has helped to demonstrate that neuronal circuits are not hard-wired and can be reconfigured—or modulated—to produce a variety of outputs or behaviors. She discovered that neurons may react to a plethora of neurotransmitters and that there may be overall rules that govern activity patterns of neural circuits.

Marder was one of the first neuroscientists to use computational biology interfaces to characterize the nervous system. Her sophisticated combination of experimental and theoretical neuroscience led to findings about homeostasis in neural systems, contributing to the current understanding of the brain as dynamic—balancing flexibility and stability. Her recent work has focused on the resilience of neural circuits—research that may be crucial in understanding how the brain may be affected by external disruptions like the effects of climate change.

For her Ph.D. work at University of California, San Diego, under the mentorship of Allen Selverston, Marder focused on the lobster stomatogastric ganglion (STG), which is a small circuit of 30 neurons that control complex feeding rhythms in the lobster stomach. Marder sought to identify all the chemical signaling molecules (neurotransmitters) in the circuit. Neuroscientists were studying various neurotransmitters individually, including acetylcholine, GABA, dopamine, and glutamate. “But nobody had the foggiest idea about why certain cells use one transmitter versus another,” says Marder. No one was asking the question of how transmitters were organized in a functional circuit.

During her thesis work, Marder decided to apply every neurotransmitter she could buy to the STG. She found that every single one influenced the activity pattern of the stomach muscles but in different ways. This was her first inkling that the same circuit could produce many outputs and that neurotransmitters can modulate activity, creating variability and promoting resilience.

Neuromodulation would become a major focus of her future research program and the lobster STG would remain an ideal system in which to study the functional dynamics of neuronal circuits. Neuromodulators—familiar ones include serotonin, dopamine, and noradrenaline—alter the brain’s performance. They help to regulate a brain circuit’s need for both flexibility and stability. Understanding their role, function, and biological mechanisms can help to explain how disorders such as depression, PTSD, and schizophrenia arise. The seed planted as an undergraduate in a psychology course had more than taken root.

After her Ph.D., Marder moved to France to complete a postdoctoral fellowship. Initially feeling out of her element, she adjusted quickly. She took to the rhythms of the lab and the city of Paris, becoming fluent in both French and channel biophysics.

In 1978, Marder returned to the U.S. and her alma mater, Brandeis—this time as an assistant professor. She dug deeper into research on neuromodulators, embarking on mechanistic studies of circuit neuromodulation and sussing out organizational rules for how these neuronal messengers work singly and collectively to produce changes in circuit performance. At the time, scientists thought circuits were hard-wired, Marder’s research demonstrated that they were reconfigurable.

In the 1990s, frustrated—and energized—by the limitations of computer models to depict a biophysically realistic model of an STG neuron, Marder embarked on a productive collaboration with Larry Abbott, then a professor of particle physics at Brandeis. Together, their teams developed self-tuning, homeostatic neuronal models that that could probe causality in circuits, essentially launching the modern era of theoretical neuroscience. Together, they developed the “dynamic clamp,” a tool that connects an artificial electrical circuit to a biological neural circuit—a fast, precisely defined brain-machine interface.

Another theme emerging from Marder’s research on neuromodulators was the concept of homeostasis in the nervous system. Her lab pioneered studies of homeostatic regulation, finding that neural circuits will return to a baseline rate of activity, or a homeostatic goal, following a change or disturbance that increases activity.

Marder’s team also found that individual variability within network parameters could still produce the same output. “Basically,” Marder describes, “it’s a way of saying that two crabs or two people have different synaptic strengths and different numbers of sodium channels and different numbers of potassium channels, but you get basically the same output. The circuits don’t have to be the same. They just have to be good solutions to produce the output.”

Arising from her work on individual variability has been an exploration of resilience in neural circuits. Marder and her team want to uncover what mechanisms promote resilience against perturbation and whether any of that individual variability provided for greater resilience for certain kinds of perturbances—all of which has to do with the robustness of the circuits.

These studies have led to interesting findings that speak to the effects of climate change. In experiments testing neural circuits in crabs against increased ambient water temperature, Marder’s group found there were upper limits at which the circuits would become dysfunctional and “crash.” They also found that those limits have shifted upward with the increase in water temperatures, suggesting how climate change impacts the neuroscience of animals living in the wild.

Marder believes that the pursuit of science should be coupled with service to the scientific community. She has been president of the Society for Neuroscience—a scientific society that boasts 36,000 members—and served on the working group for the Obama administration’s BRAIN Initiative. She is also a dedicated mentor who has pushed for diversity, equity, and inclusion at all levels of science—efforts that would resonate with her undergraduate self’s interest in civil rights law.

Marder’s contributions to understanding circuit dynamics have been recognized with many awards, including membership in the National Academy of Sciences, the W.F. Gerard Prize from the Society of Neuroscience, the Gruber Prize, the Kavli Prize in Neuroscience, and now the Pearl Meister Greengard Prize from The Rockefeller University.

From neuromodulation to theoretical neuroscience to homeostasis, variability, and resilience, Marder’s science has been guided by the desire to understand mechanisms and to methodically explicate complexity. As Marder writes in her autobiography, “Peeking into the mysteries of life never gets old.”