How Experience Changes the Way the Brain Is Wired

Behind the Science: A conversation with Margaret Livingstone

"I’m an impatient scientist." Photo by John SoaresMargaret Livingstone, HMS professor of neurobiology, investigates how we perceive our world, and, in particular, how our brain structures and restructures itself in response to our experiences.

Her research has taken her from studies of neural pathways that are perturbed by disease to explanations of why the smile on the Mona Lisa’s face seems to change depending upon where your gaze falls on da Vinci’s painting (it’s a function of where the smile registers in your visual field).

In this conversation, Livingstone discusses the evolution that has taken place in neurobiology research, the pitfalls women face when pursuing a career in academic research, and how her collection of animal skulls captivates the sixth graders she visits, just as skulls captivated her when she was a youngster.

HMS: What led you to study the brain?

LIVINGSTONE: I came to Harvard as a medical student, but then became interested in pharmacology. I had listened to this fascinating lecture by Joe Schildkraut at the Massachusetts Mental Health Center about how it seemed that monoamine neurotransmitters, such as norepinephrine, dopamine and serotonin, were abnormal in people with schizophrenia. In 1975, as a graduate student, I began working with Robert Rando in the School’s former pharmacology department, trying to make monoamine inhibitors and trying to make them differently effective for one or another of the various monoamine pathways, even though we didn’t really know much about those pathways. I thought, “Why are we messing with these pathways when we don’t even know what they do?” So I started reading about what the different monoamines did. And somehow, I don’t quite remember how the transition happened, I ended up in the neurobiology department getting my PhD.

HMS: Did you ever complete your medical degree?

LIVINGSTONE: After taking time to get my doctorate, I couldn’t go back to medicine, because according to the rules here at the time, I’d been away from it too long. So I never finished my MD.

HMS: Did that disappoint you?

LIVINGSTONE: It disappointed my father! He was furious. He had paid for medical school. But I think when I was young, I hadn’t realized what a career in medicine meant. I thought, you know, you read these medical mysteries—I used to love reading medical mysteries—and I thought medicine was more of a detective thing, but it turned out it wasn’t.

I also realized that in medicine you have to deal with sick people all the time. That was kind of an unpleasant surprise. They are miserable, they are unhappy. They aren’t fascinated by their disease. They are horrified and terrified.

I didn’t like that; it made me very uncomfortable. But I did do a rotation on a ward at Mass Mental. It was obvious to me that a lot of the people there had serious neurological impairments. Their thinking was off. And it wasn’t that they were misinformed. It was like their thinking was not going in the right way. I thought it would be fascinating to find out what had gone wrong.

HMS: Science must have an incredibly strong draw for you.

LIVINGSTONE:  Oh, yeah. I love it. My job is to ask questions. I mean, I work on the brain. I try to understand why we’re the way we are.

HMS: Did you ask questions when you were a kid?

LIVINGSTONE: No, I just did disgusting things. I can remember being fascinated by road kill. I had cow skulls in my bedroom that my mother thought were awful. I was just fascinated by them.

HMS: And still are?

LIVINGSTONE: I take my collection of skulls to the sixth-graders at the Baker School in Brookline. I bring in a bunch of rodent skulls, which all look the same. And then I have a bunch of carnivore skulls, which all look the same. And we talk about why they look the same. And then I show them this skull, which is a pig’s. And we look at the size of the pig’s brain and then look at the size of the part of the skull that contains the human brain. And I say, “Wow, there’s a lot more space dedicated to brains in that animal than in this animal.”

I then explain that there’s nothing in your brain except neurons. Everything you think you are—your personality, your hopes, your dreams—it’s neurons, and all they do is fire or not fire. And I give some explanation of how our ability to see depends on neurons firing or not firing. It’s a lot to do in an hour, but we do it. And the sixth-graders love all this. On the walls of my lab, and along the hallway, are many of the thank-you notes from those students. “Thank you for coming in to teach us about the brain. I got to see real brains and spinal cord.”

HMS: Your work is fascinating because it’s all about perception, something that seems to be so freighted with experience.

LIVINGSTONE: It is. We do the things we do in part because our brains are programmed to do things that way, and in part as a consequence of experience. I’m just trying to figure out what the link is between our genetic makeup and how we experience the world. And right now we’re looking at the development of our ability to recognize faces. Everybody knows that babies track faces, but it’s turning out that their conscious recognition of faces is probably largely dependent on early experience; there’s a lot of seeing faces in a baby’s life, right?

Your brain is actually organized into modules that process really important categories like text recognition. We’re now asking whether we can make new modules in the brains of animals that are really good at recognizing things that animals don’t normally recognize, like text, for example. And we can. Their brains form new modules. There are a lot of people who think we evolved with a module for faces. But I don’t think we did. I think we develop a module for faces by looking at our mothers.

HMS: If you were to dream the best possible outcome of your work, what would it be?

LIVINGSTONE: Oh, wow. I would love to know if we could reveal the innate genetic makeup of the object recognition pathway. And then, I’d like to know how experience modifies that ability, making you an expert at processing such things as language, facial recognition, text—things that you learn when you’re young. It can be difficult to learn a language as you age, and, for some, learning to recognize faces gets harder with time. So I would like to manipulate the system early and see how malleable it is. I think knowing these things would help people who, for example, are autistic.

HMS: You’ve been at HMS and in neurobiology for a good period of time. Have you seen an evolution in this field of science?

LIVINGSTONE:  It’s a more mature field now in that we can ask really fundamental molecular questions. When the department was first founded, it was all physiology and anatomy, which is a gross-level thing. And then Ed Kravitz came in and they discovered gabba-aminobutyric acid. That was the first molecule.

Although I personally don’t find that molecular stuff interesting, Torsten Wiesel called it “the ink in which it’s writ.” I think an awful lot of people in my department are aiming to discover how experience changes the way the brain is wired up. We’re all asking that question, at molecular, cellular and organismal levels. So, some of my colleagues are asking this at a genetic level and I’m asking it at a whole-animal level.

HMS: Has there been an increase in the number of women in the field?

LIVINGSTONE: All my postdocs are male; in my area, there are no females. We had about five for a while, and we used to go out to dinner together. Now we have wine and cheese gatherings for the female trainees in the entire department.

They’re all worried about whether one can be a scientist and be a mother, have a family. Big issue. It’s a real front-loading profession, which I think automatically biases it against women.

HMS: Front-loading?

LIVINGSTONE: You need to invest early. You need to invest between college and age 40. That’s a big span of time out of a person’s life, especially when you’re competing with people who are going at top speed between college and age 40. And I think our tenure clock is discriminatory against women. You finish college at 22; you do a couple of postdocs, you’re 30. You have 11 years to get tenure. Now, is that discriminatory against women or not? Men have a choice. They can marry a younger woman, get tenure and have kids. Women don’t have that option.

HMS: How would you describe your overall approach to science?

LIVINGSTONE:  I try to be rigorous, but usually I’m not. A lot of people think you have to set up these really fancy experiments with lots of controls at the beginning. But I like to find out what the answer is going to be, and then I’ll go back and do all the controls. I’m an impatient scientist. I like working in a field where nobody else is doing the same thing, and I don’t have to read all the literature. I worked on monoamines when nobody was working on them, and I worked on flies when nobody was working on fly learning. I don’t like making incremental steps in a gang of people all making the same incremental steps. I don’t think anybody likes that.

HMS: Of the things that you’ve been able to unravel in your work, what was the most surprising?

LIVINGSTONE:  The modular organization of the visual cortex.

HMS: You hadn’t anticipated that?

LIVINGSTONE: No. The idea that things are functionally segregated in various ways because of activity; that was interesting.

Ocular dominance columns form by activity. It starts out with a baby. It happens because the activity in each eye is correlated with itself and not with the other one. And so, they segregate. I think you get face cells segregating because you see noses and eyes at the same time, and you don’t see them in the same place or the same time as you see windows and doors. It’s likely the same functional segregation—activity-dependent sorting—that my colleagues are hoping to find a molecular explanation for.

HMS: What do you do when you’re not doing science?

LIVINGSTONE: I read. Anything. I read murder mysteries, Alice Munro, David Foster Wallace.

HMS: Foster Wallace, he’s an interesting brain to watch.

LIVINGSTONE:  No kidding.

HMS: Have you found situations in literature that pertain to neurology?

LIVINGSTONE: Yes. The last book that hit me that way—you know, Proust is a neuroscientist of a kind—was War and Peace. There’s a dream sequence in which Pierre wakes up and realizes that what he was dreaming just before he awoke was, in fact, what had been going on around him in the real world. I think that’s the way dreams occur. That although it seems they are built from all this random stuff, a random collection from your past, they are really a reflection of the sensory input your brain has received from what has been going on around you. The sixth-graders love this idea, too.

HMS: I also must ask you about your email signature. What’s that little person on a bike about?

LIVINGSTONE: I’m a militant bicyclist. That’s my helmet right behind you.

HMS:  Oh, it’s a brain!

LIVINGSTONE: Yes. When my older son was first born, I found it in a remainders bin at Toys ’R Us. I was buying diapers. I wish I’d bought six of them.

HMS:  I don’t think I’ve ever heard someone describe herself as a militant bicyclist.

LIVINGSTONE: I feel very strongly that people shouldn’t be driving around in cars, especially those SUVs with one individual in them. It’s my planet, too.