David Clayton, neurobiologist

By observing the mental machinations behind bird songs, this fan of zebra finches has found important clues about our own brains. Interview by Donna Hesterman

March 28, 2011

Photo by Brian Stauffer

David Clayton is no bird fancier, but he has hundreds of colorful feathered friends in his lab. He says they can teach us a lot about learning—not just in bird brains, but in our own.

Clayton, a neurobiologist from the University of Illinois at Urbana-Champaign, studies how DNA inside cells in the brain responds to social cues received from other individuals. He uses zebra finches as models for our own cognitive processes because, among other similarities, we learn to communicate as youngsters by listening to our parents. Adult zebra finches convey a variety of social cues to their children, mates, and neighbors through their songs.

Perhaps that intersection of hard science and personal expression strikes a chord with Clayton, an aspiring songster himself who began his career with a double major in biochemistry and journalism.

Clayton spoke at the February 2011 meeting of the American Association for the Advancement of Science in Washington, D.C., as part of a panel of experts in brain research. SciCom’s Donna Hesterman snared him for a chat about his work.

Why zebra finches? Other animals use vocal communication too, right?

"A zebra finch learns during a discrete period in adolescence, when the young male is very impressionable. He goes through this period of babbling before he learns to sing"

Yes, other animals communicate, but they don’t make very good lab animals. Elephants, well, there’s an obvious problem with that. Cetaceans, whales, and dolphins all communicate, and that would be informative because they are mammals like us. But again, they are difficult to keep in a lab.

Zebra finches are a powerful model organism because they are easy to breed, and they do well in a domesticated environment. But really, the fact that they are songbirds is the key.

Half the birds on the planet are songbirds. Other birds—like chickens, emus, or hawks—do not sing. So just comparing the brain of a singing bird with one that doesn’t gives us some insight about where language and communication circuitry is housed in the brain.

How do they learn their song?

Only the males sing, and they learn their song by copying a tutor during about a 90-day period during their adolescence. Each bird sings a unique song that is a slight variation of the song he learns from his mentor. Once the learning period begins, he works on his song until he reaches adulthood at about 3 months of age. At that point, the learning stops, and the song becomes “crystallized.” It doesn’t change for the rest of his life.

What does that tell you about their brains?

We’ve learned there is a circuit with two pathways that intersect in the output from the forebrain, and that output controls all of the physical gyrations of the singing behavior. One path is solely responsible for the moment-to-moment physical motions that produce the singing, like manipulation of the syrinx—the sound-producing organ just above the bird’s trachea—and breath control. If you disrupt anything on that pathway, the bird physically cannot sing.

The other pathway loops off through the basal ganglia [a core region of the brain] before it feeds back into the output circuit. That seems to be the pathway responsible for learning. If you disrupt that pathway, it doesn’t affect the song after it is learned. But if you mess with it while the bird is learning to sing, it screws up the learning the process.

And what does that tell us about our own brains?

There are formal parallels between the finches and humans with regard to behavior during the learning process. Zebra finches are very colonial, social animals like we are. The males and females form lifelong monogamous pairs, and both are actively involved with parental care. The song the male sings is used to establish the initial pair bond, and later to communicate with his mate as sort of a social cue that keeps her close to the nest.

Learning occurs during a discrete period in adolescence, when the young male is very impressionable. He goes through this period of babbling before he learns to sing, and that is shaped by the tutor’s song over about two months.

Following that, you have a lifelong period of continued learning where they come to recognize the songs of neighbors and other relatives. We’ve made a lot of progress over 20 years analyzing the different neural circuitry responsible for these different phases. It tells us a lot about where to begin looking for similar pathways and parallels in the human brain.

Why don’t the females sing?

Females start to develop the brain circuitry needed for singing, but for some reason that process stops in adolescence and the circuit is never completed.

We sorted that out by using brain cultures of very young birds—basically, slices of brain in petri dishes. We administered hormones like estrogen and testosterone. We found that the males’ brains were actually producing the hormone that initialized the process of building circuitry for singing. The hormone wasn’t coming from the gonads, as one might suspect. The DNA of the cells in the male brain was coded to start the process.

We first tried experiments on whole animals, administering hormones to see if we could block or encourage the development of circuitry for singing. But it didn’t work. We would have had to administer a toxic dose of hormones to a bird to get an effective dose to the brain.

But if you have a slices of brain in a dish?

Then you can get the effect.

So, what does your lab look like?

My lab is spread over four locations on the University of Illinois campus. I have a foot in two separate interdisciplinary institutes. Each of them has the normal laboratory component with desks and genome research equipment for 40 to 50 people, and then an animal care facility in the basement.

We keep anywhere from 200 to 800 birds between each. It’s an aviary with large communal cages where the birds can form mating pairs, build nests, and raise their young. Last year we introduced 10 new couples, and they have generated a population of 75 birds.

We’re using them to get a new baseline for zebra finch behavior, because much of the data we have on record was observed in birds in the wild. But our birds in the lab have been in captivity for generations, so we want to see if their behaviors have changed over time as they’ve adapted to life in the lab. We’re gathering tons of data—for example, the amount of time each individual spends allopreening [a social grooming behavior], beak boxing, singing, and sitting on the nest.

Those behaviors trigger gene expressions in the brain that you’re interested in?

Yes. For example, we might take a pair of birds and put them in the isolation booth with a hidden video camera to record their response. We make it as naturalistic as possible, and then we play a recording of a zebra finch song. It may be a familiar one, or it may be the song of a bird they are hearing for the first time. The song initiates a response from the birds that we record on tape. But then the exchange ends with a rapid euthanasia.

Wait. How does that go? Do you use a dart?

No, we have inhalant anaesthetics that are nearly instantaneous. And then we do a very quick dissection and analyze the gene expression with equipment that can analyze millions of sequences simultaneously to see which genes were expressed as a consequence of hearing the song.

We’re working on new technology that is non-invasive, where you use infrared fiber optics to send light through a living bird’s brain to get information about brain activity in real time.

Do they wear a tiny little helmet or something?

Exactly. James Lee, a student, used 3-D printer technology to engineer the prototype.

What 's next for you?

We’re shifting the field away from thinking about individual molecules and focusing instead on networks of interactions. We’ve found a thousand different gene products in the brain that are being modulated up and down on different time courses, all following exposure to a novel song. We’re puzzling with how to untangle all of that. That interface between the social component—a new song—and the chemical reactions that it spurs in the brain is a very complex interaction.

And this is all in the “effort to tease apart the logic and design of molecular networks involved in bird song?”

Yes. That’s very good! Where did you get that?

On your website.

We’re also working more with one gene that is expressed in the bird’s song-learning circuitry during adolescence. We’ve determined that the gene is suppressed in the adult birds, and that may be why the song never changes. What’s interesting is that the same gene turns out to be central to the development of Parkinson’s disease in humans. Something about the gene being misexpressed or misregulated in human DNA appears to contribute to the development of the disease. We’re trying to get a grant to study that further.

Your work receives a fair amount of press. Does that have something to do with your journalism degree?

I think the press comes as a result of my study organism. The birds are something everyone can see, and it makes my work a little more accessible. As for the journalism, that was just a point in my life when I was exploring a lot of things. I’ve always had this conflict between my literary, creative side, and my analytic, literal self.

I play guitar and was a musician in my undergraduate days in Athens, Georgia where I did my undergraduate work. They had this great music scene back in the 1980s. I even had a brief partnership with Michael Stipe at one point. We performed together and I wrote songs, but eventually I had to tell him that I was giving it up so I could concentrate on my biochem studies. He was actually crushed at the time. But he went on to do great things with R.E.M., so I obviously didn’t hold him back.

Do you think there is any connection between your own interest in music and the fact that you chose birdsong as a vehicle for studying the brain?

It is a nice little symmetry, isn’t it? I don’t know if there is a correlation. But it probably does affect my intuitive resonance about the topic. It has also been a way to blend these two very different parts of my character and life history.

Donna Hesterman, a 2011 graduate of the Science Communication Program at UC Santa Cruz, earned her bachelor's degree in history from the University of Florida and her master's degree in wildlife science from Auburn University. She is a veteran of the U.S. Marine Corps. She worked as a reporting intern at the UCSC news office, the Santa Cruz Sentinel, the Woods Institute for the Environment at Stanford University, and the Scripps Institution of Oceanography news office. She is now a science writer for the University of Florida news office.

© 2011 Donna Hesterman