If you’re reading this, your brain weighs about three pounds; that’s a little more than the average cantaloupe. Three pounds may not sound like much, but as a percentage of body mass it’s comparatively enormous. A sperm whale’s brain, for example, is as big as a beagle — but it’s tucked in a 30-ton frame.
We’ve known about humans’ huge brains for a long time, but only this year have scientists published a possible explanation: a string of DNA that seems to make human brains develop more quickly and with greater complexity. It’s a fascinating discovery that sparks as many questions as it answers. And that, in a nutshell, is the life of a neuroscientist. Because, as Carol Barnes explains in this interview, for all we’ve learned about the human brain, it remains in many ways mysterious, deep, and irresistibly promising.
Q: Philosophers were writing about neuroscience in 500 B.C. When did we see big shifts in what we know about the brain?
A: In the early ’70s, the actual, physical basis for how memories are laid down in the brain was discovered. That was huge. Early on, scientists were trying to figure out how a cell stored information. Then we realized it wasn’t about individual cells — it was about how multiple cells communicated with one another.
We know that now, but our understanding of it is still changing. It’s only in the past decade or so, for example, that mainstream neuroscience has fully accepted that our genes are constantly changing, and that just in having this conversation the methylation state of your DNA is being altered, which changes how your neurons are functioning to form this memory.
Q: Was the idea of “neuroplasticity,” that our brains continue to grow and change and adapt later in life, a paradigm shift?
A: It was, and it’s been one of the fundamental concerns in my life, actually. When I was in graduate school in the ’70s I was thinking about neuroplasticity a lot. I went to the literature trying to figure out what was known about brain aging, and the picture was horrible. It was like, “You get old, you lose all these cells, you become senile.”
I was up against the brick wall of this belief that plasticity just turns off. My Ph.D. thesis was about how that was wrong. There’s really very little cell death in the normal aging brain. The neurons you’re born with die with you when you die. There’s plenty of plasticity in the old brain, but it took me and others decades to break down that myth.
Q: Yet something does change, right? For most people, there’s some kind of cognitive decline as we age.
A: Yes, brains do change as they grow older. Individual synapses, the links that let neurons communicate, can get pruned back or change function so that they don’t work the same way. But the overall plasticity is still there. It’s one of the spectacular things about the aging brain: You can use whole-brain systems to solve a problem that you used to only use one system for. Just like when you injure a brain area, other systems are beautifully engaged to take over. That’s partly what my research program is about today: trying to optimize plasticity and lengthen the span of cognitive health.
Q: So focusing on connections vs. cells was big. Getting past the idea of the doomed, decaying brain was big. What does neuroscience tackle next?
A: There’s still so much we don’t know. Glial cells! We know they clean up debris from the extracellular space. We know there are glia involved in immune response, and there are glia that make the myelin sheaths that go around axons. They have so many distinct flavors, and we know a lot about them individually, but we need to better understand their interactions with neurons. They make up half the brain — they’re pivotal!
And then, just as we were myopic years ago in looking at single cells, we’ve been myopic in not considering what else is going on in the body. For example, we’re pretty convinced today that changes in the gut biome could have profound cognitive ramifications. This is a wild speculation, but those people with the right balance of biotic components and so forth may be those who are predisposed to age more successfully. That’s a hypothesis we’d really like to test and hopefully will test here at UA.
And we need to understand groups — ensembles of cells across the brain. We need to understand how all these cells from many different areas work together to produce behavior. And to do that, we need to map the circuits.
Q: Are we making progress there? Given how complex our brains are, is mapping them even possible?
A: That’s one of my favorite questions because I think we’re on the verge of huge breakthroughs. Just in the last few years, we’ve been able to take away all this “cloudy stuff” — remove the lipids, but keep all the neurochemicals and wiring constant — and look clearly into the brain to actually identify single connections. Here at the University of Arizona, we’re working to develop microscopes that are completely novel designs created by astronomers and optical scientists and biomedical engineers to help us identify all the cells and circuits engaged in specific behaviors.
Q: What will they give us that we don’t have today with, say, functional MRIs?
A: Essentially we’ll get an exact snapshot of brain activity during a behavior, where MRIs can only give us a rough idea based on averages. Exactly which cells are active moment by moment? If we can capture those instants of activity across the whole brain — and we think we can — it will mean a huge step toward understanding the circuits involved. And that’s really the precursor to fixing damaged brains. I don’t want to understand something just to understand it. I want to understand it well enough to manipulate something that can optimize cognitive health.
Q: What’s the horizon for that snapshot? Are we talking five years? Fifty?
A: There’s a truism in science that none of us has a crystal ball. We’ve already developed technologies that record from many cells at once, and we use those in human neurosurgery today. So we’re improving these methods all the time. When will we get to precisely map the circuits of individual behaviors? I don’t know. But I’m an optimist, so I’m saying in my lifetime.
Q: As an optimist, how do you feel about the state of the field today? Does anything keep you up at night?
A: I do worry about the next generation of scientists. There are many labs around the country that are either pulling way back or closing because of lack of funding. Today, some institutes at the National Institutes of Health are turning down as many as 96 percent of research proposals. Philanthropy, therefore, becomes more and more critical, but I’m still afraid we’re going to lose a generation of scientists, and you don’t regain that ground easily.
These kids are smart and enthusiastic. They want a challenge, and they’re exactly what we need right now. But they don’t have to be scientists; they could do many other things. I really don’t want to see people leaving science because of how hard it is to get funding. I want them to come in to the lab every day fired up about what’s possible and that next discovery, thinking, “Today is going to be the day. Today is going to be the day!”
DNA and the Brain
For decades, scientists thought DNA was fixed: You got it at conception, and (barring vandalism by out-of-control molecules) it floated unchanged until the day you died. Only recently did we learn that DNA is in constant flux, and its changes affect our daily lives.
As one highly simplified example, B vitamins help your body feed methyl group chemicals to your DNA, enabling certain brain cells to work at the top of their game. As we age, this ability to methylate can wane, compromising DNA function in ways that have domino effects on memory and other brain activities.
Brain Biology 101
When it comes to brain cells, neurons get all the attention. They conduct signals. Most have lots of branches at one end (dendrites) and one long arm at the other (an axon).
Axons from one neuron connect to dendrites on another, and those points of connection are the synapses that change with age, affecting brain function.
Those structures have dominated the neuroscience red carpet, but in addition to neurons the brain has vast armies of glial cells (glia in plural). Glia are helpers with lots of functions. If neurons were riders for the Pony Express, glia would be all the people who made sure the horses were groomed, fed, and watered after a long, hard ride.
The Plastic Brain
The “plasticity” of the brain is not a reference to Barbie and Ken. Here, “plastic” means “changeable.”
In the early 1970s, neuroscientists began letting go of the mistaken belief that after a certain young age the brain could only deteriorate. Today, we know that the physical structures of the brain can become more complex and enriched throughout life.
This neuroplasticity means that functions like memory and learning can potentially improve continuously, even in our senior years and even following brain injury.
Carol Barnes and the McKnight Brain Institute
Carol Barnes is a Regents’ Professor in the departments of psychology, neurology, and neuroscience, director of the Evelyn F. McKnight Brain Institute at the University of Arizona, associate director of the BIO5 Institute at the UA, and past president of the Society for Neuroscience. Her research explores brain changes in aging and how those changes affect memory and other abilities.
The McKnight Brain Institute is committed not only to research and to training future scientists but also to aggressive outreach, sharing the latest knowledge on healthy aging and how to protect brain function throughout life.
The McKnight Research Foundation has pledged to match up to $5 million of donations raised toward establishing a $10 million permanent endowment for the Institute. More information is at embi.arizona.edu/make-a-gift-today.