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Thanks to new tools and techniques, including advances in machine learning and the ability to track subtle and rapid chemical fluctuations in the brain, Mooney and Duke neurobiology professor are beginning to disentangle the molecular signals that drive learning for its own sake.

In new research March 12 in the journal Nature, the team put male juvenile zebra finches into individual soundproof rooms where they could practice their songs at will.

In zebra finches, only the males sing; young birds learn their courtship song early in life by first listening closely to their dad and memorizing his song. Then, like babies learning to talk, they begin to babble, their squeaks slowly becoming more song-like. By practicing their songs and listening to the results, gradually they figure out how to produce the right notes and rhythms to match their mental template of their dad’s song.

It takes a zebra finch chick about three months from hatching to become a proficient singer.

To Mooney, a longtime rock 'n' roll fan, the males’ practice sessions are a bit like the for The Beatles. “The Beatles might have done a hundred takes” before they were satisfied, Mooney said. Similarly, “these birdsong data sets get so big so fast.”

That's where Pearson’s team came in. To get a handle on the data, they developed a machine learning model that can analyze the thousands of song renditions and score each attempt.

“This way we can track learning on a moment-by-moment basis,” Pearson said.

“Some tries were a little better, and some were a little worse,” he added. Generally the longer the birds worked at it, the better they got.

As the birds gradually mastered their tunes, the team also measured the level of dopamine released in the birds’ basal ganglia, a part of the brain involved in learning new motor skills.

Dopamine is one of the brain’s chemical messengers, transmitting important signals about learning, reward and motivation from one neuron to another.

To monitor dopamine, the researchers used tiny sensors made from genetically modified proteins that glow when particular neurochemicals are released in the brain. The technology makes it possible to track brain activity that is largely invisible to common methods based on measuring electrical signals.

What they found surprised them. Whenever a bird practiced, dopamine levels in the bird’s basal ganglia started to ramp up. It didn’t matter whether they hit all the notes or missed the mark. In other words, any effort at singing activates signals in the brain’s reward pathways.

The birds’ dopamine surged more when a bird performed better than was typical for their age. The signal was slightly weaker when they regressed.

The better they performed for their age, the more dopamine increased, said first author Jiaxuan Qi, who did the work as in neurobiology at Duke.

Dopamine has long been known to play an important role in how humans and other animals learn from external rewards and punishments.

Take, for example, a child studying because they want to get a good grade or avoid a scolding. Or consider a rat learning to press a lever for food.

But birds don’t need carrots or sticks to learn how to sing. Because the birds were alone during their practice sessions, singing away in a soundproof room, they weren’t getting any external feedback on how they were doing.

“Nobody's telling the bird if he’s an honor student or going to be sent to detention,” Mooney said.

Instead, the findings suggest that dopamine acts like an internal “compass” to steer their learning.

The team’s research helps explain how learning still occurs even in the absence of external incentives. The researchers also found that dopamine isn’t the only chemical signal required for such learning.

Qi was able to show that another chemical messenger called acetylcholine can trigger dopamine release in the bird’s brain when it is singing. It works by binding to a different part of the neurons, giving the bird an extra dopamine boost when it belts its ballad.

When the birds were given drugs that blocked dopamine or acetylcholine signaling in the basal ganglia, the birds made less progress, Qi added.

“Learning basically comes to a halt,” Mooney said. “The bird still sings a lot, but he doesn't seem to be able to learn from it.”

The potential implications go beyond bird brains, Mooney said.

“These findings translate across species,” Pearson said. “The brain regions and neurochemicals involved -- namely the basal ganglia, dopamine and acetylcholine -- are shared by mice, primates, humans. Essentially every animal with a backbone.”

Studying how birds learn to sing can help researchers better understand how humans learn other motor skills such as talking or juggling or playing an instrument. In that sense, Mooney said, “birdsong learning is very similar to what children do when they spontaneously acquire these remarkable skills.”

Dopamine signaling problems in the basal ganglia have also been linked to a number of diseases, including Parkinson’s and schizophrenia.

“It's really important that we understand these regions, and the bird is a means of getting at those principles,” Pearson said.

“Of all the scientific frontiers that remain, the brain is probably the most poorly understood, and it's fundamental to being human,” Mooney said.

This research was supported by grants from the National Institutes of Health (5R01 NS099288, RF1 NS118424, F32 MH132152 and F31 NS132469).