Back in the 7th century B.C., Egypt's King Psamtik I is credited with performing one of the first science experiments in history, at least according to legend.

Curious about the origins of human language, he ordered two newborns to be raised on an isolated island by a mute shepherd. On pain of death, no one could speak in the children's presence. In this way, Psamtik hoped to see what language they would naturally speak when they grew older.

Some years later, when the children were brought to court, they babbled but spoke no language the king or his advisors could identify. Eventually someone interpreted a syllable or two as the Phrygian word for “bread,” so the king concluded that Phrygian was the original human tongue.

Despite his flawed conclusions (and appalling ethics), old Psamtik was pursuing a question that still intrigues researchers and the public to this day.

Despite the vast leaps in science since Psamtik's day, the answer to this puzzle still eludes us. Nowadays scientists would explain the king's results by noting that, while children obviously have the capacity and drive to speak, they can learn speech only if they are exposed to language during a critical period of their development. If they don't hear language during that period, they'll never learn to speak. Hence Psamtik's children could babble, but could not speak a language. (Any resemblance to Phrygian was purely coincidental.)

But such an explanation, obviously, leaves untouched the more profound question of how genetics, brain anatomy, neurology and biochemistry interact to allow each child to learn to speak-and in different ways as well. Learning and memory-indeed, how the brain functions at all, particularly in humans-remain profound mysteries that defy straightforward approaches. Unlike ancient potentates, those who would investigate such questions are obliged to employ scruples in their work. As a consequence, scientists today make progress in learning how the human brain works by carefully studying parts of that organ that have useful analogues in other animals.

In understanding learning and memory, remarkable advances have come from a surprising quarter-the study of the brains of songbirds.

Frank Johnson, an FSU neuroscientist, sums it up this way: “Speech is one of the things that sets us apart from other animals, that makes us special. If you want to understand our special-ness, you need to study some other animal that shows this-and the finch is one of the more remarkable of them all.”

While many animals communicate vocally by instinct, only a few-including dolphins, whales and songbirds-must, like humans, learn to use their voices by imitating an adult, Johnson said. Experimental work with marine mammals is difficult and costly, but a number of songbirds such as the finch make ideal laboratory animals for such study.

Research on songbirds' brains has grown rapidly since the mid-1970s. Today a number of major research universities-Rockefeller, Duke, Caltech, UCLA, the University of Southern California and the University of Illinois among them-have songbird research labs.

Johnson heads FSU's songbird lab, where he works with research associate Ken Soderstrom (now an assistant professor at East Carolina University) and graduate students Osceola Whitney and Clayton Jones. The lab focuses on studying the zebra finch, a tiny, sweet-singing bird often kept as a pet. (The name comes from the black-and-white stripes along the male's throat.)

Among zebra finches, only males sing (although, in some songbird species, both sexes do), Johnson said. Like children learning to speak, the finches learn to sing during a critical period of their development.

Johnson's research aims to illuminate just what is so critical about the critical period as well as the related question of why males sing and females don't. His efforts have led to the surprising hypothesis that behavior influences brain structure and have incidentally lent credence to two bits of popular wisdom-“practice makes perfect” and “use it or lose it.”

Much of the work in Johnson's lab involves studying the differences between juvenile and adult brains of both males and females. Finding such differences-in brain structure and gene expression, for example-can help explain what is happening in the brain that allows learning to occur.

“Humans are super-learners for language when they are very young,” Johnson said. “A child soaks up the language he or she hears spoken, and easily learns to understand it and reproduce it. Exposure to speech during this critical period fine-tunes the brain to hear and produce the sounds of the child's native language. It's not that humans can't learn languages as adults, but it's relatively difficult.”

Many other behaviors in both animals and humans depend on learning during a critical period. And in humans it seems to be the onset of puberty that locks such learning into place and cuts off the critical period, Johnson said, bringing to an end the easy learning of many things.

“The same thing occurs in these birds,” Johnson said, “but it is cleaner, more absolute.”

Human adults can and do continue to learn many things. But-like Psamtik's children-a zebra finch that did not learn to sing as a juvenile cannot learn to sing as an adult, period.

“If you raise male birds with only females around, isolated from any male song, then as an adult they will have no song,” Johnson said. “They will still try to sing, but it will be the bird equivalent of a bunch of gibberish.”

Why Don't Females Sing?

At least above the genetic level, both male and female zebra finches are born with all the hardware they need to sing, Johnson said. Songbird brains have discrete regions devoted to learning and producing song. In species where the females sing, these regions in the female brain function just like they do in the male. In zebra finches, both sexes initially have these regions and, as far as anyone can tell, they are identical, said Johnson.

“But during the critical period for learning, the male brain regions involved in singing grow quite dramatically, whereas in the female neurons die and the regions shrink. It is almost like a naturally occurring neurodegenerative disease.”

Understanding how and why neurons die in the female's brain may help lay a foundation for understanding how diseases such as Alzheimer's take their terrible toll in humans. Likewise, understanding the factors that promote growth of neurons may someday help doctors devise treatments for neurological diseases and brain injury. Before any such applications can develop, a storehouse of answers to basic scientific questions on brain function first has to be created; ergo, Johnson's work.

Inside finch's brains, their song regions connect to a bundle of neurons that control the bird's vocal apparatus. Early on, Johnson thought that perhaps females don't sing because this essential connection is missing. But when he mapped the bird's brain circuitry, he found that the connection was intact in females. “The thing is still there,” he said, “it's just never being used.”

Thus the function of the female's song regions-if one exists-remains a mystery. They may be simply vestigial-there, but serving no purpose, sort of like a male's nipples.

After 20 years of studying this phenomenon, scientists began to coalesce their findings into essentially two hypotheses as to why male zebra finches sing and females don't, Johnson said. The first idea held that the bird's hearing itself sing somehow triggers the processes that cause growth of the song regions in the male. Since the female doesn't sing, it doesn't get the feedback, which in turn leads to the death of neurons. This idea proved to be a dead end, however.

“You can deafen birds,” Johnson said, “and their song regions still develop completely normally.”

A deafened male zebra finch never learns an adult song, but it does sing a kind of babbling song, and its brain's song regions grow just as do those of a hearing male, he said.

The second theory says that differences in sex hormones cause differences in the brain. Males hormones make the song regions grow, which allows the male to learn to sing. Meanwhile, female sex hormones cause the song regions to degenerate, so the female cannot learn to sing.

This idea, too, foundered when confronted by experimental fact. Treating a male zebra finch with drugs that block hormone receptors or prevent hormone synthesis does not make a male brain look like a female brain. A female treated with male hormones will sing (thus showing that the capability exists), but not nearly as well as a male. The treated female's song regions grow a bit, but end up only half the size of a normal male's. This fact suggests, Johnson said, that the growth does not represent the natural mechanism that causes growth in the male brain.

Use It Or…

Thinking on this puzzle led Johnson to come up with another idea. Since both males and females start life with the brain regions and vocal apparatus needed for singing, perhaps the real difference between the sexes lies in the still-unidentified brain region that initiates singing. In males, the region initiates song, so the males sing. In females, no song is ever initiated, so the female never sings.

Johnson's idea is that the act of singing itself causes the male's song regions to grow. Lack of singing causes the female's song regions to degenerate. In other words, use it or lose it.

“It's a little bit of an oddball idea, but what we're saying is that these changes in the brain are not the cause of behavioral changes, but the result of behavioral changes.”

Johnson's view is the opposite of that proposed in the sex hormone hypothesis. In that view, hormones cause changes in brain structure, which in turn change behavior. But Johnson says he's found evidence that behavioral differences actually trigger the rise of physiological differences in brain structure.

The traditional view has been that genetic or developmental differences in the brain produce differences in behavior. “That's sort of a classic way to think about relationships between brain and behavior,” Johnson said. “How can behavior change the brain?”

Well, Johnson said, many scientists have shown that an animal's behavior can alter gene expression in the brain. For example, in songbirds each bout of singing initiates a new round of gene expression in brain regions that control song. So, if singing can trigger changes in gene expression, he reasoned, then those changes in gene expression surely ought to be capable of changing structures in the brain.

Practice Makes…

Not surprisingly, of late Johnson has been busy running experiments to gather evidence to support his hypothesis. One of his findings may resolve yet another puzzle that has long stumped zebra finch researchers.

A young male learns only one song, the song of its father. At first the young bird listens attentively while the adult sings. Eventually the juvenile begins to practice making the individual sounds that compose the song.

“The bird's initial attempts at singing, which we call subsong, don't sound like anything. The analogy is to babbling in human infants,” Johnson said.

Once the male bird has mastered the sounds, it must practice putting them in the proper order, a phase of learning called plastic song. “The analogy,” Johnson said, “would be that, when a human being is learning language, you see a lot of word order mistakes.”

By the time a zebra finch reaches adulthood, the song has become recognizably the father's (though it may vary by a few notes).

The puzzle is this: One of the brain's important vocal regions, called the robust nucleus of the archistriatum (mercifully abbreviated RA) overgrows during plastic song. In other words, as the juvenile matures, the RA reaches maximum size during plastic song, then shrinks somewhat in adulthood.

Using a computer system that detects and records songs, Johnson discovered that the birds sing more often during plastic song (when they are practicing) than they do as adults. On average, a young bird sings 1,500 times a day during plastic song, compared to only 400 times a day as an adult.

In this study, Johnson did not directly show that more singing correlates with a larger brain region. Nonetheless, Johnson's result fits nicely with his idea that behavior-singing the song-causes changes in brain structure. More singing during plastic song causes the RA to grow larger. Less singing as an adult causes the RA to shrink.

Johnson has found that birds that sing the most during plastic song have the highest quality songs as adults. This finding mirrors the common-sense notion that more practice leads to better performance-practice makes perfect. (What is surprising is the amount of practice necessary to learn his song-the average zebra finch practices his song 50,000 times!) Other experiments provide more direct support for Johnson's ideas.

“To test the idea that behavior influences the growth of brain structures,” Johnson said, “we need to be able to increase or decrease the amount of song a bird produces, without harming the bird.”

Drug Test

To get a handle on the question, Johnson uses two distinct approaches, one using a drug and the other using the availability of food as a means of influencing behavior.

For the first approach, Johnson's lab uses a class of chemicals called cannabinoids, named from the psychoactive compounds found in cannabis, or marijuana. As by now even aliens probably know, such chemicals can powerfully effect behavior. Less commonly known, however, is that the brain naturally produces a variety of behavior-modifying chemicals-collectively called neurotransmitters-that influence not only learning and memory, but types of behavior thought to be largely voluntary, including singing. One class of natural neurotransmitters that cannabinoid drugs mimic-called endocannaboids-appear to be specifically involved in the regulation of higher cognitive functions, such as perception and memory, as well as the control of voluntary behavior.

Work by Soderstrom in Johnson's lab showed that song regions in the zebra finch brain are rich in cannabinoid receptors, tiny sites within the brain's neural network where molecules of the chemical can attach and begin influencing behavior. The sheer number of the sites was a clear indication that these neurotransmitters play a prominent role in zebra finch singing.

When Johnson dosed both adult and juvenile zebra finches with a synthetic cannabinoid, he found that singing decreased in both groups. And when he gave the birds a drug to block the cannabinoid receptors, the birds sang more and became more active. In other words, block the receptors and singing goes up. Stimulate the receptors and singing goes down.

The most interesting result, however, came from a comparison of the adult and juvenile birds. Under the influence of cannabinoids, both groups sang less. But there was no change in the quality of the adult's song, Johnson said.

Juveniles, however, were still learning to sing during plastic song. The cannabinoids caused them to sing less, and the quality of their final adult song suffered.

These results show, Johnson said, that the drug interferes with learning as opposed to degenerating a bird's song-singing ability. Apparently the drug acts by reducing practice during the critical period when the bird is learning its song, although Johnson concedes it's also possible that the drug interfered with the bird's ability to remember what it had previously practiced.

Although Johnson has not yet done anatomical studies to correlate these results with changes in the size of brain structures, the results are consistent with his use-affects-structure hypothesis.

The implication for humans is obvious as well, Johnson said. Although no scientist would project results from bird studies directly to humans, Johnson's experiments join a growing body of research showing that endocannabinoid neurotransmitters play a key role in the development of learning and memory, and that young people may be particularly vulnerable to the effects of drugs (e.g., marijuana) that interfere with endocannabinoid signaling in the brain.

Singing for Supper

Johnson's second approach for manipulating the amount of singing a zebra finch does is environmental. First he had to figure out what element of the zebra finch's environment stimulates singing, and then find a way to manipulate it without harming the bird.

In collaboration with Michael Rashotte, veteran FSU psychologist (recently retired) and renowned expert in avian (bird) physiology, Johnson tested food, water and temperature, and found that lack of food immediately causes less singing-even before the bird has a chance to get hungry. So it is the presence of food that stimulates singing, rather than hunger inhibiting singing, he found. (As an aside, Johnson reasons that the specific stimulus is probably visual-seeing the food-although he has yet to test this idea. Many studies have shown that rather than relying on smell, birds primarily use sight to identify food and estimate its quality.)

Caged zebra finches usually have a supply of food available at all times. So to manipulate the amount of singing, Johnson controlled the times that food was available.

Zebra finches sing mostly in the morning, rapidly tapering off to just a few songs in the afternoon. And they do most of their eating late in the day. So Johnson divided a number of adult males into two groups matched for activity, similar complexity of songs and similar number of songs per day.

One group, the timed-access group, had food available only for the last six hours of daylight. The second group continued to have food available all day. The second group was dubbed the ad lib group because the birds were at liberty to eat whenever they chose.

Johnson was careful to see that both groups ate the same amount of food and that body mass remained stable for both groups, thus ensuring that the timed-access birds were not suffering from lack of nourishment or energy. And indeed the health and overall activity of the two groups was identical. The only difference was in the amount of singing.

The ad lib group continued to sing as normal, about 400 songs a day on average. The timed-access group sang only about a third as many songs. But, Johnson said, the quality of the songs remained the same for both groups. When he examined two key song-producing regions of the brain, he found that these areas were smaller by 40 to 50 percent in the timed-access group. In contrast, the sizes of brain regions not involved in singing were identical.

These results provide the strongest evidence yet of Johnson's idea: Growth of the song-producing brain regions is a function of use. Less singing leads to smaller brain areas. The behavior changes the structure of the brain.

To illustrate what he may be seeing in a tiny bird, Johnson recalled a 1995 study of violin players. Violinists use their left hands a lot, and a certain area of the brain is responsible for the left hand. In this study the violin players were brain-scanned while their left hands were stimulated.

Researchers found that the brain area controlling the left hand was larger in the violin players than in non-players. Furthermore, the earlier the age at which the violin players began playing, the greater was the difference. The implication-consistent with Johnson's hypothesis-is that use affects the amount of brain devoted to the left hand.

The idea that practice leads to improved performance is hardly startling. But the idea that use can actually cause brain structures to grow (and lack of use can cause them to shrink) calls into question the commonly held notion that our brains (and perhaps our talents and intelligence) are fixed by genetics and incapable of much change thereafter.

More evidence is needed before Johnson's hypothesis can be considered proved. But Johnson and other scientists are at least beginning to map the workings of the brain at the genetic, biochemical, structural and behavioral levels.

Without question, the human brain is the most complex and least understood lump of matter in the universe. If we listen very carefully, a tiny songbird with a cheery voice may lead us to an understanding of some of nature's most profound mysteries.

Bird Brains

Some may scoff at the gray matter of our fine-feathered friends, but researchers have discovered that songbirds such as the zebra finch exhibit a brain organization surprisingly similar to that of humans.

The central nervous system of all vertebrates follows the same general plan, says Frank Johnson, a neuroanatomist and head of FSU's songbird lab-a spinal cord topped by a brain divided into a number of major segments. But the brains of some songbirds possess a key characteristic that makes them more human-like than any animal outside the mammalian kingdom.

Higher cognitive functions such as learning and memory for complex tasks reside in a brain structure known as the telencephalon. Both bird songs and human speech originate in this segment. In most animal species, the percent of the brain devoted to the telencephalon reflects the animal's lifestyle-its strategies for dealing with the outside world.

For example, as a small scavenger, a rat doesn't do much thinking or planning. Rather, it needs to respond quickly to survive, and its brain's architecture emphasizes this need, Johnson said. Nearly half of a rat's entire central nervous system is made up of a spinal cord and a brain stem. The critter's telencephalon accounts for only about 38 percent of its basic neural machinery. Pigeons, too, are scavengers who need fast reflexes to respond to a variety of different situations. And the pigeon's brain is organized very much like that of a rat.

In humans-animals commonly less renowned for their instincts than their abilities to think, plan, learn and memorize-the telencephalon makes up fully 81 percent of the brain. Songbirds apparently need sizeable telencephalons to help them learn to sing-the structure makes up 64 percent of a zebra finch's brain, for example. Thus, in its peculiar proportions, a songbird's brain more closely resembles our own than does a rat's-the most common lab animal on the planet-even though genetically, rodents are by far our closer relative. -D.W.