The Eyes Have It: A Conversation with Neuroscientist Michael Stryker

Part 2 of 2

One of the great wonders of vision is that we learn to see with our eyes still closed. The waves of activity that connect the retina to the visual cortex in the third trimester of pregnancy are the womb’s version of a shakedown cruise.

Cells with different duties learn where they are in relationship to each other. They make maps and get oriented and organized in the still uncharted waters of our developing cortex. Then, with birth, a new world appears. Cells prepared to see are now trained to see by experience.

The first six weeks of life are critical. Various medical conditions that blur or distort the visual input – from cataracts to strabismus – distort the cortical map. The eye is normal, but it cannot see. And if both eyes develop normally, there is still another developmental hurdle to leap. The input from both eyes must match, so that we see the world in exactly the same way.

Exploring how this happens has kept Michael Stryker, PhD, busy for decades. And as the techniques and the technology reach a point where it’s possible to actually see anatomical connections between cells take shape – sometimes only in a matter of days – Stryker’s work has reclaimed the phrase “shock and awe.”

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Podcast transcript

Jeff Miller: Hello I’m Jeff Miller and welcome to Science Café, today I’m with Michael Stryker, a professor of physiology and a member of the Keck Center for integrative neuroscience at UCSF, welcome Michael.

Michael Stryker: Welcome… To my office (laughter)

Miller: I’d like to start out by asking you what do you think the is the role for science in our society?

Stryker: I think science is the basic knowledge that allows technological advances that have made our society so much more healthy than we were hundreds of years ago, and I think really the most significant cultural accomplishments of the last hundred years are scientific – you can point to earlier times in history when the real creations were what we think as artistic, renaissance art in Italy and so on, but the progress of science now is the increase in human understanding that really is a significant event in human culture. We actually appreciate how many things work that were just an utter mystery before.

So I think the role in science is in part a demonstration of human capacity to create things. Science is creating stories about how the world works. And the difference between scientific stories and other stories is that scientific stories are correct, (laughter) so they not only have consequences for action in the world, like new toys, new devices, better food production, but they also have consequences for thinking about ourselves in relation to the universe and appreciating that things don’t ‘just happen,’ they happen for a reason, they have causes and the human mind can understand those things.

Miller: So there’s this intellectual side but there’s also practical—prosperity, security, health, all that.

Stryker: Yes. And it’s difficult when we live sometimes with political leadership that isn’t based in reality in the hope that wishful thinking will make it so, is contrary to the way science works. And so I think science is the ultimate reality-based policy – is what science is for. It’s quite different from the faith-based policy which we’re seen in a lot of our political leadership recently, where they believe that actions don’t really have predictable consequences.

Miller: What would you say is the state of science in society today?

Stryker: It depends over what time period you’re talking about, but if you think it over the decades, I think science is really vibrant and healthy, its very very exciting to be doing science now, particularly to be doing biology and neuroscience where we’re really beginning to figure out how things work in a way that was inconceivable when I was a grad student, so I think science basically is very healthy – I think there are threats to it. There’s a know-nothing political threat that may in the long run pose a problem and of course in the last few years there’s been a very serious threat to the integrity of science in the United States because of reductions in real levels of funding.

Miller: You mentioned money there, when I think of money I think of graduate training, the infrastructure of science, and I read something recently about what’s called the Post-Science Era, which is applying a business model to this infrastructure of discovery , and saying essentially that America does not necessarily have to invest in this infrastructure, this educational infrastructure, that has graduate students learning things in labs that in fact if it’s cheaper to do that elsewhere it’s better for the U.S. to exploit the discoveries that others make and not bother spending public money on this now, what do you feel about that?

Stryker: I think that’s a really foolish idea, that the U.S. by virtue of having a really superior method for supporting science and for giving independence for young scientists to pursue their dreams has been a tremendous beneficiary of scientific talent from all over the world. From Europe, from Russia, from China, from elsewhere, and from many parts of the much less developed world, from India, there’s been a tremendous brain drain of people in whom those countries invest a great deal in training them and many of the most talented ones come to the U.S. and stay here and I think are responsible for much of the vibrant science in this country and for much of our progress in technology. California benefited enormously early on by having the best public university system in the world. And for California taking out of state students to train for an education isn’t a burden, it’s an investment because the people who come from out of state and get educated here, then stay here and start companies and create the modern economy in California. So it’s certainly the case that you can profit from discoveries made elsewhere, and I think in the course of this debate there are a number of examples that have been pointed out, advances in semi conductors, recent advances in light emitting diodes that were done in laboratories in Japan that are being exploited economically in the U.S., and there are lots of examples from Europe where our industry is benefiting from discoveries made elsewhere, but that wouldn’t happen if we didn’t have the whole infrastructure of discovery and innovation and technology and business coming together, and it comes together around the great universities.

Miller: Well, the brain also comes together in a wiring sort of way, so I’m wondering if you could explain to the listeners the nature of your research and just give us an overview of what you understand as to the wiring system that takes shape in the brain during the developmental stages which is sort of the center piece of your research effort at UCSF?

Stryker: Well it’s an amazing thing, the brain has zillions and zillions of neurons and it only works because they’re connected together in the right way, each neuron talks to the right other neurons and tells them something and other neurons process the information further and end up allowing us to make decisions and do actions. And the subject I work on is how these correct connections get formed, and we work on it in a very early stage of the highest part of the brain, the neocortex, the part that’s really big in human beings compared to other animals, and it’s the part of the brain we think with, a lot of our conscious experience, perhaps all of it--

Miller: This is the part that developed within the last hundred thousand years or so? I know there’s debate about that, but…

Stryker: Yeah, there’s debate about that, but… Neanderthal man had a pretty big cortex and modern man has an even bigger one. But basically, very very smart mammals have bigger cortices. The neo cortex has existed for a very long time but it’s much much bigger in relation to the rest of the brain in us.

Miller: Can we anticipate that it will continue to grow over the eons?

Stryker: I don’t know, I think it’s a really interesting question, whether evolution is frozen or whether it’s continuing, I don’t have any well-informed opinion on it.

Miller: I’m going to take you down a side road here because it occurred to me if the brain increased in size, I guess that would be in some ways determined by the size of the birth canal in females, so…

Stryker: Maybe, although you could imagine having smaller neurons that grow bigger post natal than there is now, I don’t see any reason in principle that couldn’t happen. The real question is whether cultural issues, I mean – human culture and human civilization have changed the selective pressure that gave rise thru evolution by natural selection to larger and larger brains, in the hominids and the monkeys, the pre-human apes that had smaller brains that presumable evolved into humans, that, I believe and I don’t think anyone really knows the details – I mean I’m convinced that no one knows the details-- that was presumably due to the advantage of human intelligence in insuring survival. And making it more likely that the offspring of intelligent parents would be more likely to survive and those intelligent parents had bigger brains.

But it may well be those cultural factors, the way civilization works now, we’re not actually selecting for people to be more intelligent, it’s very hard to know, these are very vague issues and in the time horizon of any individual human being they have no impact (laughter). So they’re not issues that I can make myself care about.

Miller: OK, I’m going to circle you back to the main road now, so we have this brain taking shape, this wiring being laid down, and it has to be very specific-

Stryker: Right. And so it’s specific in large part because they’re a number of different cell types in the brain and those cell types have chemical signals on them that allow them to recognize other cell types. But the question of how the whole brain gets set up, it’s a complicated set of instructions that these cells have about where they should grow, who they should connect to and how they do it. And we know that there are a number of different signals involved, and we know some of the details about these signals because we study mice in which one of the molecules that is part of one of these signaling systems is defective and we see that the brain gets miswired in different ways.

But the striking thing about the brain, as say compared to a computer which has to be wired up correctly, is the brain has to be useful during the time it’s wired, it isn’t put together in a factory while it’s not working and then the good ones are selected and the bad ones are thrown away, instead the brain starts functioning at a much simpler level, and the neurons grow and make more and more connections during our life as a fetus and during our early post-natal life and it takes quite a while for the brain to get wired up properly.

Miller: How long? Three years, four years?

Stryker: Well, in the parts of the brain I study, it clearly takes throughout fetal life and throughout the first year and a half or so, with development preceding very very rapidly in the first six weeks or so after birth. So that’s a period of time when we know from animal models that the connections are being formed in a preliminary way, and then those preliminary connections are being refined during normal development. And they’re being refined by two different kinds of signals, and we’ve actually studied this in mice where the corresponding period of time is the first few weeks of life.