The First and Forever Bond

When rat babies have it really good, their mom gives them a lot of two things: licking and arched-backed nursing. But not every rat litter has it so good. Sometimes, the mother isn’t as attentive. The question is, why? Part of the answer is in the chemistry of the brain.

Maria Boccia, scientist at the Frank Porter Graham Child Development Center, and Cort Pedersen, professor of psychiatry, have shown that in rats, neurotransmitters (substances that nerve cells use to signal each other) regulate how much nurturing a mother gives her baby and how that baby will treat her children when she becomes a mother.

Even in humans, that first attachment—emotional and physical bond—between parent and child influences all later relationships, most scientists say. It sets up our expectations for what others will bring to us and for what we’re expected to give. Boccia and Pedersen think that the first relationship is so important because it “breaks in” the physiological system that regulates attachment. For example, if babies don’t get enough nurturing from parents, certain neurochemical systems may not mature. “So it may be harder for those people to feel emotional closeness when they grow up,” Pedersen says. “Not that it would be impossible for them. But their early experience could influence the degree to which their emotions or behavior can be influenced by certain chemical systems.”

Boccia and Pedersen have learned quite a bit about how those chemical systems work in rats. The researchers are especially interested in the neurotransmitter oxytocin. More than 20 years ago, Pedersen discovered that when he administered oxytocin into female rats’ brains, it would stimulate mothering behavior. Since then Pedersen and other researchers have found that it plays a role in other social attachments and in female and male sexual behavior.

In a rat mother, oxytocin is important in two specific behaviors: licking her pups and nursing them while standing in an arched-backed posture, giving them maximum access to her nipples. Researchers have known for about five years that rat pups who get more licking and arched-backed nursing from their mothers can handle stress better than other rats. Stress for a rat is anything unfamiliar. Reaction to stress can be measured using a maze that has two runways with high walls and two with no walls. Rats who got more “good mothering” will spend more time in the open parts of the maze and less time hiding in the walled parts. And, their levels of the stress hormone corticosterone don’t rise as high.

Pedersen and Boccia have found that these mellow rats also have a lot more oxytocin receptors in some parts of their brains. (After the rats are euthanized, researchers examine the rats’ brains, using radioactive labeling to count the numbers of receptors.) “It looks like early nurturing behavior from mom can alter the development of oxytocin receptors in some parts of the brain,” Pedersen says. “And the more of these good types of mothering behaviors a rat gets when it’s a baby, the more oxytocin binding there is in certain parts of the brain.” The difference in amount of oxytocin receptors between rats who got more “good mothering” compared with those who got less was 250 percent in some brain areas.

The researchers “created” the differences in mothering behavior between the two groups of rats by separating the babies from their mothers. When rats are separated from their mother for short periods (15 minutes once a day), their mothers respond by giving the babies more licking and arched-backed nursing. Rats who are separated longer (three hours a day) get the opposite—less mothering. The female rats who get more licking and arched-backed nursing as pups also show more of these behaviors to their babies when they grow up. It appears that the mothers’ nurturing behavior is changing the amount of oxytocin receptors in their babies’ brains for the long term.

So it looks like this is sort of a nongenetic mechanism for transmitting individual differences across generations quite quickly,” Boccia says. “When we want to look for individual differences in behavior, we usually look for differences in the genes. But in this area, it’s clear that our environment, our experience, can change our physiology.” What isn’t clear yet is exactly how that happens or, as Boccia puts it, how the “neural circuitry” works.

The researchers do know that oxytocin seems strong enough to substitute for some nurturing behavior. When a rat pup’s mother leaves it, Pedersen says, the pup “starts screaming its head off, in an ultrasonic range. That’s probably its signal to mom, ‘Hey, I’m over here, come and pick me up.’” But if the researchers inject the pup with oxytocin before they remove the mom, the pup won’t cry. “That suggests that when the pup is with the mom, and is getting groomed and nursed, oxytocin is being released in the pup,” Pedersen says.

In fact, Pedersen and Boccia found that oxytocin is so powerful that they can use it to create the “good-mothering” and “bad-mothering” groups, skipping the separation step. They simply inject oxytocin into one group of female pups and inject another group with an oxytocin antagonist—a substance that keeps oxytocin from binding to receptors. When the rats grow up, those who received oxytocin in infancy show the same results as those who got more mothering, and those who receive the antagonist behave similarly to those who got less mothering.

Can a chemical really take the place of grooming and nursing? “I’m amazed that we’ve been able to get these effects in rats,” Pedersen says. In people, however, it’s probably a lot more complicated. “When you get into people and monkeys, by decreasing or disrupting early relationships, you can completely mess up the ability to bond or show normal social behavior at all in the adult,” Pedersen says. Of course learning and personality influence how those early relationships affect us, but so do brain chemicals. Perhaps one day there will be a medication that could help people with attachment problems by changing their brain chemistry.

Before that can happen, though, there’s much more to find out about oxytocin. For instance, while the researchers know that oxytocin is important in initiating maternal behavior, they had thought that it played no role in maintaining it. This seemed so because when they blocked oxytocin receptors in the brains of rats who had just delivered babies, the mother rats showed no maternal behavior to their pups. But if oxytocin receptors weren’t blocked until the mother rats had several days of mothering experience, the moms continued to show normal maternal behavior.

The results changed when Pedersen and Boccia observed this second group of rats more closely. Instead of just determining whether or not the mothers showed maternal behavior, they recorded exactly how often the rats showed it. They videotaped the rats and noted their behaviors every 15 seconds during a 105-minute period. The tapes showed that the mothers whose oxytocin receptors were blocked after several days of mothering did continue to show normal mothering, but did less licking and arched-backed nursing. “Even after the mothering behavior has become well established, the oxytocin in the brain of the mom is continuing to influence how much of the behavior she shows,” Pedersen says.

Pedersen and Boccia hope to soon take their work to the next step—studying the effects of oxytocin in monkeys. First they must work out details, such as finding an oxytocin antagonist that works well in monkeys and has few side effects. “Since we know so much about monkeys’ social development and attachment that parallels humans,” Boccia says, “it would be a really important step in helping us learn how much of what we’re seeing in the rats generalizes to human beings.”

Breaking the Chains of Aggression

Jean-Louis Gariépy likes to think of himself as an optimist. But that’s not always easy for a developmental psychologist to do. Gariépy, associate professor of psychology, explains that people want simple answers when it comes to behavior. “They want to be able to say that you behave this way because of your genes, because you were beaten as child, because you have raging hormones. Those things are easy to understand,” Gariépy says.

But Gariépy sees development as much more dynamic. Like his mentor the late Robert Cairns, cofounder of the Center for Developmental Science, he believes there are many windows of opportunity throughout an individual’s life in which behavior can actually be changed or, as psychologists like to put it, “reorganized.”

I’m trying to provide experimental proof that early experience in life, although important, doesn’t necessarily mean doom and gloom when it goes bad,” Gariépy says.

Gariépy’s proof comes from studying mice that he’s been breeding for 42 generations. (To observe the same number of human generations, he would have had to begin around 900 A.D.) There are two lines of mice: one that’s been bred to be low in aggression and one that’s been bred to be high in aggression.

Early tests show the effects of separation on the mice. In one of the experiments, both high-aggression and low-aggression pups were separated daily from their mothers for brief periods of time. When returned, the low-aggression pups received extra care from their mothers. In the days following these experiences of separation, they licked and handled their pups more than mothers of the same line whose pups always stayed with them.

While high-aggression mice naturally provide more care to their pups than low-aggression mice, in this experiment, separation had no effect on the adult response to stress. That’s because, when returned to their mothers, high-aggression pups did not receive any more maternal care than if they had not been separated from their mothers. So even without their mother’s handling, high-aggression adult mice are able to regulate their stress better than low-aggression adult mice. It is only with handling that the low-aggression mice are able to regulate their stress as well as high-aggression mice.

Other researchers have shown that handling and licking of pups causes the release of serotonin in the hippocampus (a part of the brain). This facilitates the expression of a gene that manufactures the stress-hormone receptors that control the amount of the stress hormone corticosterone in circulation in the blood. The more serotonin released, the more receptors produced. And the more receptors in the hippocampus, the easier it is to shut down the production of corticosterone. If there aren’t enough receptors, then the corticosterone builds up because higher levels are needed to shut production down. As a result, low-aggression animals that had been handled as pups were better able to regulate stress as adults than those who were not.

Gariépy explains that maintaining low levels of stress requires a constant flow of serotonin in the hippocampus because the corticosterone receptors in the brain are constantly replaced. Knowing this, Gariépy reasoned that there must be conditions encountered later in life that help maintain this flow of serotonin.

To see if he was right, Gariépy took low-aggression adolescent pups that had been separated from their mothers for brief periods of time at infancy and exposed them to low-aggression peers. He compared these pups to the low-aggression ones that he had kept in isolation since the first experiment. He found that among the peer-exposed adolescents, there was a further reduction by another 50 percent in stress hormone levels as compared to those mice that had only been separated from their mothers in infancy.

If behavior were fixed from infancy, then you would never have this effect,” Gariépy says.

Gariépy also took the high-aggression adolescent pups who had been separated briefly from their mothers at birth and exposed them to high-aggression peers. The high-aggression pups constantly tried to attack their peers, preventing a constant flow of serotonin. As a result, there was no change in their levels of corticosterone when the adolescent mice were exposed to stressful situations, such as being placed in a brightly lit arena.

Gariépy believes the reason the low-aggression adolescent mice had a further reduction of stress hormone when exposed to their peers was tied to the fact that, when grouped, these animals behave in a friendly manner instead of attacking each other. “These social conditions,” Gariépy says, “achieve naturally what we try to achieve pharmacologically by prescribing Prozac to stressed and depressed individuals.”

With regard to humans, Gariépy suspects that individuals who have low levels of stress hormones as adults have been fortunate enough to maintain relationships throughout their lives similar to those created by their parents. Likewise, individuals whose parents caused them high levels of stress as infants have continually been exposed to relationships that cause high stress levels. Because of their negative experiences as infants, these individuals come to peer groups with the expectation that they will be rejected. Because they haven’t learned coping skills, they usually are.

But if you were to throw something into the equation where individuals were forced to adjust to a situation that calls for new behaviors, there’s a possibility that you could change their biology,” Gariépy says.

For example, Gariépy points to a time when he was working as a graduate student at a day care center in Montreal. If the caregivers were having problems with a withdrawn or insecure (low-aggression) child, then they would take that child from his own peer group and place him in a younger peer group. Here the child was not rejected because the younger kids looked up to him and provided him with a leadership role. On the other hand, when there was an hyperactive (high-aggression) child, then they would place her in an older peer group. Sometimes the child would start to punch the others in the group but would soon learn the older kids wouldn’t tolerate that type of behavior. And the older peers also didn’t reject her because they felt responsible for the kid. “It worked in every single case and rapidly,” Gariépy says.

You can never totally change an individual,” Gariépy says. “But if you pay attention, for instance, to transitions in the lives of individuals from one institution to another, you can capitalize on that transition and reorganize kids in a good direction.”

The Mysteries of Instinct

Are we shaped by our experiences even before we’re born? Yes, says Gilbert Gottlieb, but in ways that we don’t fully understand. For much of his 30 years of work, Gottlieb, research professor of psychology at the Center for Developmental Science, traced the prenatal beginnings of behaviors that had been thought to be instinctive.

Beginning in 1961, Gottlieb studied mallards and wood ducks at his research station in Wake County. He and his assistants collected eggs and incubated them in the lab. After the experiments, with the help of Gottlieb’s wife, Nora, the researchers raised the birds to flight stage, then released them.

Gottlieb’s team measured ducklings’ and embryos’ responses to their mothers’ calls in several ways. One was attaching a tiny electrode to the embryos’ bills to measure the rate of bill clapping. This up-and-down movement of the bill would speed up when the ducks recognized and responded to a call, but would stay at a baseline rate when they didn’t. The researchers also tested whether the ducklings would approach and follow a call; they put the ducklings in a chamber with two hidden speakers equal distance from each other, each playing either the maternal call of the ducklings’ own species or of a different species. A baby duck would make its way toward the speaker playing the call that it preferred, eventually huddling against it.

Early on in his work, Gottlieb thought that maybe ducklings learned the maternal call of their species before birth, since a mother duck starts uttering her assembly call before the babies hatch. But Gottlieb was surprised to find that birds who had been raised in an incubator before hatching, and therefore couldn’t hear their mothers’ calls before birth, still preferred their own species’ maternal call over the calls of others.

Gottlieb was sure there had to be some experience that triggered the ducks’ responses to their mothers’ calls. He thought maybe it was the ducklings’ hearing their own and their brood mates’ calls before hatching. He tested this idea using a procedure that he had perfected with John Vandenbergh, a colleague now at North Carolina State University. About three days before hatching, the duck embryo’s bill moves into the air space at the large end of the egg, and it begins breathing. At that time the researchers could cut a hole in the air space of the egg without doing the bird harm. Using this procedure, Gottlieb temporarily devocalized the embryos while they were still in their eggs, using surgical glue to keep their vocal membranes from vibrating. They would regain their voices in a week or so.

Gottlieb’s team discovered that the ducklings who had been devocalized, and so hadn’t heard their own embryonic calls before hatching, didn’t respond specifically to the maternal call of their own species. Half of the time they preferred the maternal call of a chicken.

What puzzled Gottlieb was that the ducklings’ embryonic calls and their mothers’ calls sounded nothing alike. To figure out what feature of the embryonic calls was cueing the ducklings to respond to the maternal calls, the researchers manipulated features of the embryonic calls, such as frequency modulation or repetition rate, before playing them to devocalized embryos. Then they tested the ducklings to see if they responded to their mother’s calls after hatching. “We would just vary one thing at a time, and then when we would find an instance where the duck didn’t respond to his mother’s call, we knew ah, that feature that we changed, that’s the one,” Gottlieb says. For wood ducks, if the frequency modulation (how the frequency of the sound increases or decreases over time) of the embryonic calls was changed, they couldn’t recognize their mothers’ calls later. For mallards, the key feature was repetition rate (the speed at which the notes are emitted).

Gottlieb still kept finding surprises. He assumed that the repetition rate of the mallards’ embryonic calls must be similar to their mothers’ calls. But, no. The maternal call is emitted at about four notes per second on average, but if Gottlieb played the devocalized embryos a recording of embryonic calls at four notes per second, they didn’t recognize the maternal call. The ducklings had to hear the embryonic calls in their normal variable pattern of one to six notes per second. “The variation in repetition rate is the critical feature of the mallard embryonic call, but there isn’t a direct relationship to the maternal call,” Gottlieb says. “But they do learn something about the maternal call from hearing the embryonic calls. I use the term ‘learn’ because I don’t have another word to use, though it’s not direct learning.”

This phenomenon is known as “nonobvious experience.” There are other examples, such as when Gottlieb’s friend Joshua Wallman, now at Brooklyn College, found that baby chickens, who normally gobble up meal worms, won’t touch the worms if they’ve never seen their own toes move. (Wallman covered the chicks’ toes from birth.) A researcher at the University of Tokyo, Nobuo Masataka, discovered that monkeys raised in a lab weren’t afraid of snakes, as wild monkeys usually are. The difference was that the lab monkeys had never been exposed to any kind of animal except for other monkeys. But when the lab monkeys were fed live insects, instead of just monkey chow, they were afraid of snakes too.

As a result of these kinds of experiments, scientists are much more wary about using the label innate or instinctive,” Gottlieb says. “But it hasn’t led to any big revolution because this is so hard to understand.” It seems there is more mystery in the development of animals, and certainly humans, than we’d like to think.

Catherine House was formerly a staff contributor for Endeavors.

Gottlieb’s book, Synthesizing Nature-Nurture: Prenatal Roots of Instinctive Behavior, won the Eleanor Maccoby Book Award, which recognizes works that promise to have a profound effect on the discipline. He has also been recognized by the Society for Research on Child Development for “distinguished contributions to child development.”