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Troy Littleton earns Award for Excellence in Undergraduate Advising
April 21, 2020

The Department of Brain and Cognitive Sciences is honored to announce this year’s awards for faculty, graduate students, and undergraduates. These individuals have contributed exceptionally to the academic and intellectual life of our department.

Faculty Awards

BCS Award for Excellence in Undergraduate Advising: Troy Littleton

As one nominator said:

“He is my go-to faculty member for academic and career support, and his door is always open when you need it the most
There have been challenges that I’ve faced here that feel insurmountable, but whenever those times hit, I could talk it through with Professor Littleton. With his guidance, we would work towards a solution
 And when I did pull through, when I succeeded beyond my own imaginable expectations, his office was the first place I went to for celebration.”

BCS Award for Excellence in Undergraduate Teaching: Myriam Heiman

This award is based on student evaluations and nominations. Myriam co-teaches 9.09, Cellular and Molecular Neurobiology, and 9.18, Developmental Neurobiology. Some comments from her evaluations show why she is so admired as a teacher:

“Myriam was a great professor. She went through the material at a perfect pace, and really emphasized general understanding of the topics we were learning about. She was also very welcoming to questions.”

“Professor Heiman is thorough, passionate, and insightful. The devil is always in the details and she does an excellent job highlighting the significant points in the context of the course.”

BCS Award for Excellence in Graduate Teaching: Sasha Rakhlin

Sasha teaches 9.521, Mathematical Statistics—an Asymptotic Approach, and co-teaches 9.520, Statistical Learning Theory and Applications. As with the undergraduate teaching award, this recognition is based on both course evaluations and student input. Some comments from Sasha’s evaluations were:

“Very high-quality teaching, with good explanations of difficult ideas and methods.”

“The material by nature requires you to get dirty, and I think he went through the details at the correct level.”

“One of the best lecturers I’ve had at MIT.”

BCS Award for Excellence in Graduate Mentoring: Mark Harnett

This award is based on student nominations. As one of them said of Mark:

“He has been exceptional in supporting the students with their projects and making sure they have all they need to succeed in their experiments, both technically and conceptually. He also always made sure we are prepared for important steps in grad school (qualifying exams and committee meetings) and can deliver excellent presentations. He has always dedicated time to teach fundamental aspects of patch clamp electrophysiology to all rotating students, and is always available, and happy, to answer questions.”

BCS Postdoc Award to an Outstanding Postdoctoral Mentor: Roger Levy

Roger was nominated by one of his postdocs and endorsed by the Building 46 Postdoctoral Association.  His nominator wrote:

“Roger is a brilliant leader and role-model. Roger is compassionate and understanding of the academic and social issues that postdocs face and is someone whose guidance I seek and respect. He has supported me as I try to decide whether or not to pursue an academic career, really proving to me that he has no stake in the outcome besides my wellbeing. He also has [a] tremendously strong moral ethic that reflects science at its best: from issues ranging from conflicts of interest to open access and funding transparency.”

Finally, we have added a special recognition this year:

BCS Award for Excellence in Teaching: Robert Ajemian

Robert is a research scientist in the McGovern Institute who teaches 9.53, Emergent Computations Within Distributed Neural Circuits. Students in this course give exceptionally strong evaluations. For example:

“Robert’s biggest strength is his enthusiasm for the material and for the field in general 
 The course setup, with Daniel and Karthik sharing some of the instructor responsibility, was a really great feature of the course – the nature of our discussions always benefited from having a variety of expert perspectives.”

“I appreciated the fervor with which the material was presented, which made the class all the more engaging, as well as the emphasis on critical thinking and debate, which is an important but often overlooked aspect of good scientific thinking.”

Robert’s instructor scores support these comments— a 6.4 in his first year, 2018, and a 6.6 in 2019. With scores and comments such as these, it was clear that we should recognize his contributions, and we are pleased to do so.

Graduate Student Awards

Angus MacDonald Award for Excellence in Undergraduate Teaching by a Graduate Student

This award is named for an MIT alum and Corporation Member who was a key supporter of our department and particularly our undergraduate educational mission. This year we are recognizing three graduate students for exemplary teaching of undergrads based on subject evaluations and faculty nominations:

  • Maddie Cusimano
  • Mark Saddler
  • Lupe Cruz

The next two awards named for Walle Nauta, a pioneering neuroanatomist, a founding member of this department, an Institute Professor, and one of the founders of the field of neuroscience.

Walle Nauta Award for Excellence in Graduate Teaching by a Graduate Student, recognizing exemplary teaching of their fellow graduate students based on subject evaluations and faculty nominations.

  • Mahdi Ramadan
  • Victoria Beja-Glasser

Walle Nauta Award for Continuing Dedication to Teaching by a Graduate Student, a special honor for someone who has already received a teaching award from our department and has continued to be exemplary.

  • Mika Braginsky
  • Tobias Kaiser
  • Halie Olson

Undergraduate Awards

Academic Awards (cumulative GPA of 4.9 or greater)

Course 9, Year 4:

  • Katherine Collins
  • Apolonia Gardner
  • Seungweon Pak
  • Ashti Shah
  • Aaditya Singh
  • Yotaro Sueoka
  • Lena Zhu
  • Merryn Daniel
  • Jingxuan Fan
  • Stephanie Hu
  • Ohyoon Kwon
  • Habiba Noamany
  • Raimundo Rodriguez
  • Lauren Schexnayder
  • Sarah Wu
  • Irene Zhou

Course 9, Year 3:

  • Ayesha Ng
  • Albert Gerovitch
  • Kristine Hocker

Course 6-9, Year 4:

  • Alice Zhang

Course 6-9, Year 3:

  • Keith Murray
  • Michelle Yakubek
  • Jasmine Zou

Research Awards (nominated by PI)

  • Keith Skaggs (Course 9, Year 3)
  • Michelle Hung (Course 9, Year 3)
  • Ohyoon Kwon (Course 9, Year 4)

Congratulations once again to all award recipients!

Harnessing the moonseed plant’s chemical know-how
Eva Frederick | Whitehead Institute
April 20, 2020

In overgrown areas from Canada to China, a lush, woody vine with crescent-shaped seeds holds the secret to making a cancer-fighting chemical. Now, Whitehead Institute researchers in Member Jing-Ke Weng’s lab have discovered how the plants do it.

Plants in the family Menispermaceae, from the Greek words “mene” meaning “crescent moon,” and “sperma,” or seed, have been used in the past for a variety of medicinal purposes. Native Americans used the plants to treat skin diseases, and would ingest them as a laxative. Moonseed was also used as an ingredient in curare, a muscle relaxant used on the tips of poison arrows.

But the plants also may have a use in modern-day medicine: a compound called acutumine shown to have anti-cancer properties (although not tested specifically against cancer cells, the chemical has been shown to kill human T-cells, an important quality for leukemia and lymphoma treatments). Acutumine is a halogenated product, which means the molecule is capped on one end by a halogen atom — a group that includes fluorine, chlorine and iodine, among others. In this case, the halogen is chlorine.

Halogenated compounds like acutumine can be useful in medicinal chemistry — their unusual chemical appendages mean they react in interesting ways with other biomolecules, and drug designers can put them to use in creating compounds to complete specific tasks in the body. Today, 20% of pharmaceutical compounds are halogenated. “However, chemists’ ability to efficiently install halogen atoms to desirable positions of starting compounds has been quite limited,” Weng says.

Most natural halogenated products come from microorganisms such as algae or bacteria, and acutumine is one of the only halogenated products made by plants. Chemists finally succeeded in synthesizing the compound in 2009, although the reaction is time-consuming and expensive (10 mg of synthesized acutumine can cost around $2,000).

Colin Kim, a graduate student in the Weng lab at Whitehead Institute, wanted to know how these plants were completing this tricky reaction using only their own genetic material. “We thought, why don’t we ask how the plants make it and then upscale the reaction [to produce it more efficiently]?” Kim says.

“By understanding how living organisms such as the moonseed plant perform chemically challenging halogenation chemistry, we could devise new biochemical approaches to produce novel halogenated compounds for drug discovery,” Weng says.

Kim knew that for every halogenated molecule in an organism, there is an enzyme called a halogenase that catalyzes the reaction that sticks on that halogen. Halogenases are useful in creating pharmaceuticals – a well-placed halogen can help fine-tune the bioactivities of various drugs. So Weng, who is also an associate professor of biology at Massachusetts Institute of Technology, and Kim, who spearheaded the project, began working to identify the helper molecule responsible for creating acutumine in moonseed plants.

First, the scientists obtained three species of Menispermaceae plants. Two of them, common moonseed (Menispermum canadense) and Chinese moonseed (Sinomenium acutum), were known to produce acutumine. They also procured one plant in the same family called snake vine (Stephania japonica) which did not produce the compound.

They began their investigation by using mass spectrometry to look for acutumine in all three plants, and then find out exactly where in the plants it was located. They found the chemical all throughout the first two — and some extra in the roots of common moonseed. As expected, the third plant, snake vine, had none, and could therefore be used as a reference species, since presumably it would not ever express the gene for the halogenase enzyme that could stick on the chlorine molecule.

Next, the researchers started searching for the gene. They began by sequencing the RNA that was being expressed in the plants (RNA serves as a messenger between genomic DNA and functional proteins), and created a huge database of RNA sorted by what tissue it had been identified in.

At this point, the extra acutumine in the roots of common moonseed came in handy. The researchers had some idea of what the enzyme might look like – past research on other halogenases in bacteria suggested that one specific family of enzyme, called Fe(II)/2-oxoglutarate-dependent halogenases, or 2ODHs, for short, was capable of site-specifically adding a halogen in the same way that the moonseed’s mystery enzyme did. Although no 2ODHs had yet been found in plants, the researchers thought this lead was worth a look. So they searched specifically for transcripts similar to 2ODH sequences that were more highly expressed in the roots of common moonseed than in the leaves and stems.

After analyzing the RNA transcripts, Kim and Weng were pretty sure they had found what they were looking for: one gene in particular (which they named McDAH, short for M. canadense dechloroacutumine halogenase) was highly expressed in the roots of common moonseed. Then, in Chinese moonseed, they identified another protein that shared 99.1 percent of McDAH’s sequence, called SaDAH. No similar protein was found in snakevine, suggesting that this protein was likely the enzyme they wanted.

To be sure, the researchers tested the enzyme in the lab, and found that it was indeed the first-ever plant 2ODH, able to stick on the chlorine molecule to the alkaloid molecule dechloroacutumine to form acutumine. Interestingly, the enzyme was pretty picky; when they gave it other alkaloids like codeine and berberine to see if it would install a halogen on those as well, the enzyme ignored them, suggesting it was highly specific toward its preferred substrate, dechloroacutumine, the precursor of acutumine. They compared the enzyme’s activity to other similar enzymes, and found the key to its ability lay in the substitution of one specific amino acid in the active site– aspartic acid — for a glycine.

Now that they had identified the enzyme responsible for the moonseed’s halogenation reactions, Kim and Weng wanted to see what else it could do. A chemical capable of catalyzing such a complex reaction might be useful for chemists trying to synthesize other compounds, they hypothesized.

So they presented the enzyme with some dechloroacutumine and a whole buffet of alternative anions to see whether it might catalyze a reaction with any of these molecules in lieu of chlorine. Of the selection of anions, including bromide, azide, and nitrogen dioxide, the enzyme catalyzed a reaction only with azide, a construct of 3 nitrogen atoms.

“That is super cool, because there isn’t any other naturally occurring azidating enzyme that we know of,” Kim says. The enzyme could be used in click chemistry, a nature-inspired method to create a desired product through a series of simple, easy reactions.

In future studies, Weng and Kim hope to use what they’ve learned about the McDAH and SaDAH enzymes as a starting point to create enzymes that can be used as tools in drug development. They’re also interested in using the enzyme on other plant products to see what happens. “Plant natural products, even without chlorines, are pretty effective and bioactive, so it would be cool to see if you can take those plant natural products and then install chlorines to see what kind of changes and bioactivity it has, whether it develops new-to-nature functions or retain its original bioactivity with enhanced properties,” Kim says. “It expands the biocatalytic toolbox we have for natural product biosynthesis and its derivatization.”

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Written by Eva Frederick

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Citation: Kim, Colin Y. et al. The chloroalkaloid (−)-acutumine is biosynthesized via a Fe(II)- and 2-oxoglutarate-dependent halogenase in Menispermaceae plants. Nature Communications. April 20, 2020. DOI: 10.1038/s41467-020-15777-w

Stretch and relax
Lucy Jakub
April 13, 2020

Consider the fruit fly, Drosophila melanogaster. Though it’s only a couple of millimeters long, its body is intricately complex. But it began, as most animals do, as an amorphous blastula—a hollow ball of dividing cells. During embryonic development, the structures of the body emerge as cells multiply and change shape, sculpting tissues into the mature forms dictated by the genetic code. One of the first structural changes is gastrulation, during which the blastula becomes multilayered with an ectoderm, mesoderm, and endoderm. In the developing fly, this occurs through a tissue folding mechanism. The first fold is the invagination of the mesoderm, when cells fated to become muscles contract and curl inward, leaving the cells fated to become skin on the exterior.

Biologists have traditionally focused on how cells generate force to understand cell and tissue shape change. But researchers at MIT have found that there’s another important, though often overlooked, player in tissue folding: cell division, or mitosis. By combining live-imaging with genetic mutations of developing Drosophila embryos, they observed that cell constriction and division can act together to promote folding, and that mitosis interferes with the accumulation of motor proteins that allows cells to generate force.

“What the results tell us is that the cell cycle and cell division might need to be tightly regulated relative to other shape changes that are happening in the tissue,” says Adam Martin, the senior author of the study published on March 13 in Molecular Biology of the Cell. “They present a new paradigm for thinking about how tissue shape might be regulated during development, and provide insight into what might cause birth defects in humans.” Clint Ko PhD ’20, a former graduate student in the Martin lab, was lead author of the study.

In 2000, three different labs identified a genetic mutation that caused premature cell division in developing Drosophila embryos. They found that the gene tribbles, named for the fuzzy, rapidly-reproducing animals in Star Trek, regulates cell division in the mesoderm of the fly, ensuring that cells only divide at the appropriate time. When that gene is deleted, cell division occurs before the mesoderm can properly internalize. What was notable about this mutant was that the blastula never folded, and remained a ball of cells instead of an envelope of tissue with an inside and an outside. This observation led researchers to believe that cell cycle regulation somehow regulates tissue folding. But, at the time, there was no live-imaging technology to visualize how cells changed in the developing embryo.

By using a fluorescent protein to visualize chromosome condensation, which marks the start of mitosis and the cell’s preparation for division, the researchers were able to use live-cell imaging to see how premature division might be interfering with cell constriction. When a cell prepares to divide, it expands and becomes rounded, before elongating—shape changes that exert force on neighboring cells. But something else was going on, too.Specifically, researchers in the Martin lab wanted to see what was happening to networks of the motor protein myosin, which allows cells to contract, in the tribbles mutant. Myosin is the same protein that allows our muscle tissue to contract when we flex. To facilitate tissue folding in the developing fly, myosin is concentrated at the top of the cells in the mesoderm, where they form the surface of the blastula. As this myosin constricts, the outer surface of the tissue shrinks and contracts inward.

“We noticed that when the cells are dividing, the apical myosin networks that are present disappear,” says Ko. Cells that had already begun to contract relaxed when they entered mitosis, indicating that it’s a loss of contractility in the tribbles mutant that prevents folding. The researchers suspect that this reversal occurs because mitosis disrupts signaling from the gene RhoA, which regulates contractility and cell shape changes during development. An undergraduate researcher in the lab, Prateek Kalakuntla, showed that regulation of RhoA changes at the start of mitosis.

“Initially we were just curious about the tribbles mutant,” says Ko. “But then we started exploring other ways of looking at how cell divisions affect myosin accumulation in cells.” They utilized a mutation in which the gene fog, which is located upstream of myosin activation on the genome, was overexpressed. (Fog is short for “folded gastrulation.”) Cells in the Drosophila ectoderm don’t normally contract, but with ectopic fog overexpression, those cells activated myosin, too. With live-cell imaging, the researchers observed furrows develop across the ectoderm.

“It was a bit unexpected to see these tissues folding when they shouldn’t be folding,” says Ko. Specifically, the folds occurred along the boundaries of mitotic domains, regions of spatiotemporally patterned cell divisions that occur in coordinated pulses. “That led to this sort of novel idea that cell divisions—particularly when they’re in this pattern where they’re interspersed between contractile cells—can actually promote tissue folding.”

Understanding the genetic basis for tissue folding, and how our genes control the development of specific bodily features, can help determine how birth defects arise during development. “If cell cycle control is misregulated during development, it could actually alter the shape of that tissue,” says Martin. The study paves the way for further research into how exactly the location of myosin in the cell is regulated, and how it is affected at the molecular level by cell division.

“We observed that when these cells enter mitosis, the localization of myosin activators changes. But we don’t really know how it changes,” says Ko. “That would be a pretty interesting research problem, especially considering that it’s such an integral part of force generation in cells.” Kalakuntla has begun investigating what controls these regulators, which will be an avenue of future research for the lab.

Top image: Myosin networks, in green, contract cell membranes in the mesoderm of a developing Drosophila embryo. Credit: Martin lab.

Citation:
“Apical Constriction Reversal upon Mitotic Entry Underlies Different Morphogenetic Outcomes of Cell Division”
Molecular Biology of the Cell, online March 4, 2020, DOI: 10.1091/mbc.E19-12-0673
Clint S. Ko, Prateek Kalakuntla, and Adam C. Martin

Katie Collins, Vaishnavi Phadnis, and Vaibhavi Shah named 2020-21 Goldwater Scholars

Three MIT undergraduates who use computer science to explore human biology and health honored for their academic achievements.

Fernanda Ferreira | School of Science
April 10, 2020

MIT students Katie Collins, Vaishnavi Phadnis, and Vaibhavi Shah have  been selected to receive a Barry Goldwater Scholarship for the 2020-21 academic year. Over 5,000 college students from across the United States were nominated for the scholarships, from which only 396 recipients were selected based on academic merit.

The Goldwater scholarships have been conferred since 1989 by the Barry Goldwater Scholarship and Excellence in Education Foundation. These scholarships have supported undergraduates who go on to become leading scientists, engineers, and mathematicians in their respective fields. All of the 2020-21 Goldwater Scholars intend to obtain a doctorate in their area of research, including the three MIT recipients.

Katie Collins, a third-year majoring in brain and cognitive sciences with minors in computer science and biomedical engineering, got involved with research in high school, when she worked on computational models of metabolic networks and synthetic gene networks in the lab of Department of Electrical Engineering and Computer Science Professor Timothy Lu at MIT. It was this project that led her to realize how challenging it is to model and analyze complex biological networks. She also learned that machine learning can provide a path for exploring these networks and understanding human diseases. This realization has coursed a scientific path for Collins that is equally steeped in computer science and human biology.

Over the past few years, Collins has become increasingly interested in the human brain, particularly what machine learning can learn from human common-sense reasoning and the way brains process sparse, noisy data. “I aim to develop novel computational algorithms to analyze complex, high-dimensional data in biomedicine, as well as advance modelling paradigms to improve our understanding of human cognition,” explains Collins. In his letter of recommendation, Professor Tomaso Poggio, the Eugene McDermott Professor in the Department of Brain and Cognitive Sciences and one of Collins’ mentors, wrote, “It is very difficult to imagine a better candidate for the Goldwater fellowship.” Collins plans to pursue a PhD studying machine learning or computational neuroscience and to one day run her own lab. “I hope to become a professor, leading a research program at the interface of computer science and cognitive neuroscience.”

Vaishnavi Phadnis, a second-year majoring in computer science and molecular biology, sees molecular and cellular biology as the bridge between chemistry and life, and she’s been enthralled with understanding that bridge since 7th grade, when she learned about the chemical basis of the cell. Phadnis spent two years working in a cancer research lab while still in high school, an experience which convinced her that research was not just her passion but also her future. “In my first week at MIT, I approached Professor Robert Weinberg, and I’ve been grateful to do research in his lab ever since,” she says.

“Vaishnavi’s exuberance makes her a joy to have in the lab,” wrote Weinberg, who is the Daniel Ludwig Professor in the Department of Biology. Phadnis is investigating ferroptosis, a recently discovered, iron-dependent form of cell death that may be relevant in neurodegeneration and also a potential strategy for targeting highly aggressive cancer cells. “She is a phenomenon who has vastly exceeded our expectations of the powers of someone her age,” Weinberg says. Phadnis is thankful to Weinberg and all the scientific mentors, both past and present, that have inspired her along her research path. Deciphering the mechanisms behind fundamental cellular processes and exploring their application in human diseases is something Phadnis plans to continue doing in her future as a physician-scientist after pursuing an MD/PhD. “I hope to devote most of my time to leading my own research group, while also practicing medicine,” she says.

Vaibhavi Shah, a third-year studying biological engineering with a minor in science, technology and society, spent a lot of time in high school theorizing ways to tackle major shortcomings in medicine and science with the help of technology. “When I came to college, I was able to bring some of these ideas to fruition,” she says, working with both the Big Data in Radiology Group at the University of California at San Francisco and the lab of Professor Mriganka Sur, the Newton Professor of Neuroscience in the Department of Brain and Cognitive Sciences.

Shah is particularly interested in integrating innovative research findings with traditional clinical practices. According to her, technology, like computer vision algorithms, can be adopted to diagnose diseases such as Alzheimer’s, allowing patients to start appropriate treatments earlier. “This is often harder to do at smaller, rural institutions that may not always have a specialist present,” says Shah, and algorithms can help fill that gap. One of aims of Shah’s research is to improve the efficiency and equitability of physician decision-making. “My ultimate goal is to improve patient outcomes, and I aim to do this by tackling emerging scientific questions in machine learning and artificial intelligence at the forefront of neurology,” she says. The clinic is a place Shah expects to be in the future after obtaining her physician-scientist training, saying, “I hope to a practicing neurosurgeon and clinical investigator.”

The Barry Goldwater Scholarship and Excellence in Education Program was established by Congress in 1986 to honor Senator Barry Goldwater, a soldier and statesman who served the country for 56 years. Awardees receive scholarships of up to $7,500 a year to cover costs related to tuition, room and board, fees, and books.

Interested in sharpening your science communication skills?

An internship with MIT Biology can get you on your way.

Raleigh McElvery
April 7, 2020

For the past several years, MIT Biology has been training undergraduates, graduate students, and research associates in the craft of science communication. In an effort to foster professional development and share the exciting research that transpires on campus, our communications team offers science writing and multimedia internships. We develop these positions to align with the interests of our interns, who often help out on a volunteer basis. Assignments range from assisting with videos and podcasts to writing news stories and profiles, aiding with social media, and chronicling the history of the department. After honing their own skills, many of our interns have successfully competed for prestigious communications fellowships, graduate programs in science writing, and communications jobs. Take a look at what they’ve done, and contact us if you’re a member of the department interested in joining our team.

Justin Chen PhD ’18 (Spring 2017 – Spring 2018)

Justin Chen earned his PhD in Hazel Sive’s lab, using frog embryos to model human craniofacial development. As a science writing intern, he composed student profiles for the department website and articles on research papers for MIT News. After graduating from MIT, he earned an AAAS Mass Media and Science and Engineering Fellowship, which he spent at STAT News publishing breaking news and profiles of scientists. He is currently an external affairs associate at OpenBiome, where he drafts press releases, annual reports, academic publications, and patient education materials, while helping to manage the website and social media. In addition to his work at Openbiome, he authors personal essays as a writer-in-residence at Porter Square Books.

Nafisa Syed SB ’19 (Spring 2019)

Nafisa Syed earned her bachelor’s degree in Biology (Course 7), with minors in Science Writing (Course 21W) and Brain and Cognitive Sciences (Course 9). She was an editor at The Tech, MIT Undergraduate Research Journal (MURJ), and Rune Literary Magazine, while completing a UROP in Evelina Fedorenko’s lab studying the brain’s language regions. As an intern at MIT Biology, Nafisa generated content for the internal newsletter, spearheaded social media campaigns, and analyzed data displaying the distribution of life science funding across the Institute. She is currently earning her master’s degree at MIT’s Graduate Program in Science Writing.

Saima Sidik (Spring 2019 – Spring 2020)

Saima Sidik is a research associate in Sebastian Lourido’s lab, where she studies how the parasite Toxoplasma gondii causes disease. In addition to authoring articles on scientific research for her blog, 10X Objective, Saima composes student profiles for the department website and MIT News, news briefs, and archival pieces about the history of biology at MIT. Starting this fall, she will begin her master’s degree at MIT’s Graduate Program in Science Writing.

Lucy Jakub (Fall 2019- Spring 2020)

Lucy Jakub served as the editorial assistant at The New York Review of Books for two years before entering MIT’s Graduate Program in Science Writing in the fall of 2019. As an intern for MIT Biology, she writes news briefs for the department website, student profiles for MIT News, and articles on recent events, in addition to generating the internal newsletter and social media campaigns. Her work has also appeared in Harper’s Magazine and National Geographic.

Sebastian Swanson (Fall 2018 – present)

Sebastian Swanson is a fourth-year graduate student in Amy Keating’s lab, studying the principles of protein-protein interactions in order to develop algorithms for peptide design. As an undergraduate at the University of Minnesota, he served as an officer and co-chair of MinneCinema Studios, which produces a variety of multimedia projects ranging from mock TV episodes to short films. He is currently the department’s primary cinematographer, filming faculty profiles and short videos on research projects.

Are you a member of the MIT Biology community interested in honing your scientific communication skills? Contact biowebmaster@mit.edu to discuss potential internship opportunities.

Neuroscientists find memory cells that help us interpret new situations

Neurons that store abstract representations of past experiences are activated when a new, similar event takes place.

Anne Trafton | MIT News Office
April 6, 2020

Imagine you are meeting a friend for dinner at a new restaurant. You may try dishes you haven’t had before, and your surroundings will be completely new to you. However, your brain knows that you have had similar experiences — perusing a menu, ordering appetizers, and splurging on dessert are all things that you have probably done when dining out.

MIT neuroscientists have now identified populations of cells that encode each of these distinctive segments of an overall experience. These chunks of memory, stored in the hippocampus, are activated whenever a similar type of experience takes place, and are distinct from the neural code that stores detailed memories of a specific location.

The researchers believe that this kind of “event code,” which they discovered in a study of mice, may help the brain interpret novel situations and learn new information by using the same cells to represent similar experiences.

“When you encounter something new, there are some really new and notable stimuli, but you already know quite a bit about that particular experience, because it’s a similar kind of experience to what you have already had before,” says Susumu Tonegawa, a professor of biology and neuroscience at the RIKEN-MIT Laboratory of Neural Circuit Genetics at MIT’s Picower Institute for Learning and Memory.

Tonegawa is the senior author of the study, which appears today in Nature Neuroscience. Chen Sun, an MIT graduate student, is the lead author of the paper. New York University graduate student Wannan Yang and Picower Institute technical associate Jared Martin are also authors of the paper.

Encoding abstraction

It is well-established that certain cells in the brain’s hippocampus are specialized to store memories of specific locations. Research in mice has shown that within the hippocampus, neurons called place cells fire when the animals are in a specific location, or even if they are dreaming about that location.

In the new study, the MIT team wanted to investigate whether the hippocampus also stores representations of more abstract elements of a memory. That is, instead of firing whenever you enter a particular restaurant, such cells might encode “dessert,” no matter where you’re eating it.

To test this hypothesis, the researchers measured activity in neurons of the CA1 region of the mouse hippocampus as the mice repeatedly ran a four-lap maze. At the end of every fourth lap, the mice were given a reward. As expected, the researchers found place cells that lit up when the mice reached certain points along the track. However, the researchers also found sets of cells that were active during one of the four laps, but not the others. About 30 percent of the neurons in CA1 appeared to be involved in creating this “event code.”

“This gave us the initial inkling that besides a code for space, cells in the hippocampus also care about this discrete chunk of experience called lap 1, or this discrete chunk of experience called lap 2, or lap 3, or lap 4,” Sun says.

To further explore this idea, the researchers trained mice to run a square maze on day 1 and then a circular maze on day 2, in which they also received a reward after every fourth lap. They found that the place cells changed their activity, reflecting the new environment. However, the same sets of lap-specific cells were activated during each of the four laps, regardless of the shape of the track. The lap-encoding cells’ activity also remained consistent when laps were randomly shortened or lengthened.

“Even in the new spatial locations, cells still maintain their coding for the lap number, suggesting that cells that were coding for a square lap 1 have now been transferred to code for a circular lap 1,” Sun says.

The researchers also showed that if they used optogenetics to inhibit sensory input from a part of the brain called the medial entorhinal cortex (MEC), lap-encoding did not occur. They are now investigating what kind of input the MEC region provides to help the hippocampus create memories consisting of chunks of an experience.

Two distinct codes

These findings suggest that, indeed, every time you eat dinner, similar memory cells are activated, no matter where or what you’re eating. The researchers theorize that the hippocampus contains “two mutually and independently manipulatable codes,” Sun says. One encodes continuous changes in location, time, and sensory input, while the other organizes an overall experience into smaller chunks that fit into known categories such as appetizer and dessert.

“We believe that both types of hippocampal codes are useful, and both are important,” Tonegawa says. “If we want to remember all the details of what happened in a specific experience, moment-to-moment changes that occurred, then the continuous monitoring is effective. But on the other hand, when we have a longer experience, if you put it into chunks, and remember the abstract order of the abstract chunks, that’s more effective than monitoring this long process of continuous changes.”

The new MIT results “significantly advance our knowledge about the function of the hippocampus,” says Gyorgy Buzsaki, a professor of neuroscience at New York University School of Medicine, who was not part of the research team.

“These findings are significant because they are telling us that the hippocampus does a lot more than just ‘representing’ space or integrating paths into a continuous long journey,” Buzsaki says. “From these remarkable results Tonegawa and colleagues conclude that they discovered an ‘event code,’ dedicated to organizing experience by events, and that this code is independent of spatial and time representations, that is, jobs also attributed to the hippocampus.”

Tonegawa and Sun believe that networks of cells that encode chunks of experiences may also be useful for a type of learning called transfer learning, which allows you to apply knowledge you already have to help you interpret new experiences or learn new things. Tonegawa’s lab is now working on trying to find cell populations that might encode these specific pieces of knowledge.

The research was funded by the RIKEN Center for Brain Science, the Howard Hughes Medical Institute, and the JPB Foundation.