Lobster lesson
Fish tank research explains neural circuits
They are just lobsters and crabs with seemingly crude and simple brains and bodily systems. Yet Brandeis University neuroscientist Prof. Eve Marder – who has spent decades studying them – has through the crustaceans revolutionized the way scientists view the function and structure of neural circuits of the brain. Her conclusions are believed to be relevant to humans as well.
For her work, Marder was chosen by the senate of Tel Aviv University to receive an honorary doctorate, and she attended the ceremony late last month during her third visit to Israel.
She was cited, according to TAU, for “her exceptional contribution to neuroscience; her paradigm-altering work that changed the way scientists view the structure and function of brain circuits, and opened entirely new research fields; her vision in pioneering undergraduate study in the field of neuroscience almost three decades ago; her extensive list of canonical publications and major honors, including the Kavli Prize in Neuroscience; her dedication as teacher and mentor to new generations of young brain researchers, many of whom have become renowned scientists in their own right; her influential role in strengthening the role of women in science; and her valued collaborative ties with Israel’s scientific community in general, and with TAU and its Sagol School of Neuroscience in particular.”
Last year she shared the $1 million Kavli Prize, established 12 years ago by the Kavli Foundation, the Norwegian Academy of Science and Letters and the Norwegian Ministry of Education and Research to honor, support and recognize scientists for outstanding scientific work in the fields of astrophysics, nanoscience and neuroscience.
Brandeis was established in a Boston suburb as a private, nonsectarian university with a founding principle of being open and welcoming to faculty, students and staff of all backgrounds and beliefs. Named for the late US Supreme Court associate justice for 23 years, Louis D. Brandeis, who was born to Jewish immigrant parents from Bohemia, the university is driven by a set of values rooted in Jewish history and experience, including a reverence for learning, critical thinking and making the world a better place using one’s talents and actions.
AND MARDER is Jewish as well. “I attended Hebrew school for two years but didn’t have a bat mitzva. I’m afraid I don’t speak any Hebrew. My mother was born in the Bronx, New York to Jewish parents of European origin. Her father, also Jewish, was born in Vienna, Austria arrived in the U.S. at the age of 14 in 1939, and eventually established a market research firm in New York City, she said in an interview with The Jerusalem Post.
Her husband, Prof. Arthur Wingfield (from a Russian-Jewish family who immigrated to the US in the 1920s) studies memory and language comprehension in the hearing-impaired population in young and old people. He works across the hall from Eve in the Volen Center, an interdisciplinary center at Brandeis. “We met here on campus when were both on the faculty. We talk and give ideas and advice to each other,” she said with a smile.
The honor from TAU was her second honorary doctorate; the first was from Bowdoin College in Maine. “But this was the first from a university outside the US. I was very excited to get the recognition from an Israeli institution,” she said.
Marder got her bachelor’s degree at Brandeis University and doctoral degree at the University of California, San Diego. Her doctoral work on the role of acetylcholine in the lobster stomatogastric ganglion led her to singlehandedly write a paper for the prestigious journal Nature. She did her postdoctoral work at the University of Oregon and the École Normale Supérieure in Paris. Almost 30 yeas ago, Marder established one of the very first American undergraduate neuroscience programs.
She is a member of the American Academy of Arts and Sciences and the US National Academy of Sciences. Marder is a former president of the Society for Neuroscience and today serves on the US National Institutes of Health (NIH) advisory group for the BRAIN Initiative. She is a deputy editor at eLife, a prominent online scientific journal. The neuroscientist also writes often for the layman about science, politics and society.
She was previously in Israel for the inauguration of the Sagol School five or six years ago. Her second visit was to give talks at the Hebrew University. She has also spoken at the Weizmann Institute of Science in Rehovot and the Technion-Israel Institute of Technology in Haifa. She also comes to visit Israeli cousins.
Eve Marder never wanted to be doctor. “I was biology major, and I took a class in abnormal psychology. I had to write a paper for that class in 1967 about the fact that mental illness might be involved in the brain. I read a lot about the subject and decided to be a neuroscientist,” she recalled.
AS SHE didn’t like experimenting on warm-blooded animals, she ended up working on lobsters and crabs.
“Even on cold-blooded animals, when we have to sacrifice them in experiments, we do so with great respect and, of course, by minimizing discomfort and suffering as much as possible. We first put them in ice buckets for 30 minutes to cool them down before dissecting them., never in boiling water as they are to be cooked in restaurants. We hope they won’t suffer, and they die very quickly. One should realize that every life is precious. We have to use animals for brain study, but we teach these principles to all our students.”
Marder noted that zebrafish are very important new models in neuroscience research. “You can grow them in the lab and study their genetics. Their bodies are transparent when they’re young, so you can see their nervous systems, but I chose to work in lobsters and crabs to investigate their stomatogastric nervous systems. The ganglia have only 30 neurons, with interesting patterns. We can learn a lot from them about humans. We look for general principles, and it’s easier to see them in small nervous systems. You notice things you can’t yet see or study in humans,” she explained. She doesn’t claim that her work is directly relevant to humans and curing diseases, but some implications are thought to be very interesting by people who work clinically. Basic science is important, as it helps change perceptions.”
At TAU, she also made two presentations including a scientific seminar and a talk about scientific reproducibility and a second one discussing including a discussion of mistakes in science.
Lobsters and crabs are nocturnal animals and probably sleep, but it’s hard to know without monitoring their activity carefully, as they don’t have eyelids. They are seen resting often on the bottom of the fish tank. “We work with them during the day.”
She still doesn’t know if they feel pain. “They have sensory neurons that cause then to withdraw from certain types of stimuli. But this is a different thing than the human concept of pain. Nocioception – the sensory nervous system’s response to certain harmful or potentially harmful stimuli as in crabs and lobsters – is a different concept than pain,” she said.
Her lab keeps the crustaceans for days or weeks. “If left alone, most can live seven years or so. The big ones can last for 25 or 30 years, but there were giant lobsters that lived for four or five decades,” she said.
Marder’s lab has 10 undergraduate and five graduate students and four postdoctoral fellows, equally divided between the genders.
“I prefer an equal number of men and women,” she said. “Young students should be very well trained scientifically before they go to industry. In one form or another, as they are very smart, they want to be useful members of society and to spark innovation,” she added.
“Some undergrads proceed to graduate school. One who graduated a few days ago, Dahlia Kushinsky, was born in Israel and raised in the US, but she is now going to the Hebrew University to do her Ph.D. A few go to medical school after graduation.” Most of the Ph.D students first go on to post-doctoral fellowships. Then some continue in academic careers while others go into biotech companies, consulting firms and the like. Many end up in startup companies, just like in Israel, she said. Israeli scientists, she continued, “are amazing. You have some of the smartest and most-dedicated scientists I know. I know a fair number.”
HER MOST important discovery was that neural circuits are not “hard-wired” to produce a single output or behavior, but can be reconfigured by neuromodulators to produce many outputs and behaviors while still maintaining the integrity of the circuit. Neuromodulators are the physiological process in which a nerve cell neuron uses one or more chemicals to regulate diverse groups of neurons. This is in contrast to classical “synaptic transmission,” in which one presynaptic neuron directly influences a single postsynaptic partner.
Her work on the nerve cells that make up the lobster stomatogastric ganglion produced many important – if abstruse – discoveries. She was the first to work on plasticity and homeostasis, revealing more about how the brain can change dramatically during learning and development yet remain structurally stable. Her recent research examining network variability among healthy individuals shows that a variety of network parameters can produce the same behavioral outcome. This called into question a long-standing target in theoretical neuroscience to model “ideal” nerves and neural circuits.
“Most people experience things differently if they are anxious and stressed. These states change the way we experience sensory inputs and more. If estrogen levels change in females, they can change circuit activity patterns or neuromodulation. We neuroscientists look at the ways in which diffuse chemicals or local chemicals can change activity patterns in circuits. This happens all the time; sleep and wake patterns depend on the concentration of modulations. It is crucial for every moment of our day.
“My lab was among the first to study these mechanisms in details. In our system, modulators are responsible for activating and strengthening feeding systems. We wanted to understand how the gut and feeding circuits in the brain work. There are up to 200 chemical modulators in the crab, for example, including serotonin, dopamine and others. And many neuropeptides such as endorphins in crustaceans.”
As deputy editor of an online scientific journal, Marder is aware of “mistakes in science.” The scientific community, she insisted, “is trying to be more vigilant and to weed these out. We make an effort to become very transparent on how data are reported. At eLife, I want information to be described accurately so anybody can see and analyze it. Most mistakes that creep into texts are accidental; as data get more complicated, it sometimes easy for errors to happen. Peer review captures a lot of mistakes but can also miss things.”
When research is commissioned by pharmaceutical companies, “they have to be very open and transparent. There is a big push in the US to make sure drug trials are accurate and reproducible. “Everybody benefits from openness, as if companies conceal harm from their products, their reputation will suffer in the end. Fewer drugs today are barred due to harmful side effects, but sometimes issues arise after they are approved and used by millions of people. It’s natural not to see everything when drugs are tested in small populations,” said Marder.
As the Trump Administration takes over, she is concerned about whether it will affect scientific research. “GOP-controlled Congresses have generally been pretty good for funding of science. We scientists are concerned about the need to ensure that overall support for science of all kinds is high enough, I myself am doing fine, as I just received an eight-year research grant from the NIH. Young scientists often get money to help get them going and veteran researchers also often do OK, but mid-career researchers are hurting the most,” Marder concluded.