Does Puberty Make You Stupid? Lessons from Mice

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Up until 20 years ago, scientists believed that the human brain was largely mature by puberty. Apparently, they had failed to notice the irrational behavior and flaky thinking of teenagers. Now, of course, we know that the human brain continues to undergo serious restructuring well into the 20s.

Sophisticated brain-scan studies by Jay Giedd at the National Institute of Mental Health (NIMH) have shown dramatic changes throughout the teenage years as excess gray matter is pruned from the prefrontal cortex — the seat of higher-order thinking and making judgments (like not smoking weed right before your chemistry exam). Meanwhile, behavioral studies have shown what every parent already knows: teens have poor control over impulses and a tendency toward risk taking. Still, relatively little is known about how such changes affect learning or what happens at a biochemical level in the brain as teens go through their addled adolescence.

A fascinating study published in the current issue of Science helps fill in a bit of the picture, drawing evidence from that research-friendly fellow mammal, the mouse. The authors, a team from State University of New York Downstate Medical Center, wanted to look at whether the ability to learn is affected by changes in brain chemistry that occur at puberty. They devised a task that was relatively complex (at least for a mouse) and required learning how to avoid a moving platform that delivered a very mild shock.

"This is higher-order learning, and it takes multiple trials to learn," explains Sheryl Smith, a professor of physiology and pharmacology at Downstate. Prepubescent mice mastered the task quickly. Postpubescent mice also did quite well. But mice in the throes of puberty, which occurs at age 5 weeks, couldn't seem to get it through their furry little heads.

In a series of elegant experiments, Smith and her collaborators showed that this temporary learning deficit could be traced to a remarkable change that occurs at puberty in the hippocampus, a region of the brain that is involved in remembering places and integrating other kinds of learning. The change affects the GABA neurotransmitter system. GABA, which is present in all mammals, inhibits or down-regulates nerve signals, as opposed to exciting them; this calming, relaxing system is activated by tranquilizers like Valium and the popular sleep drug Ambien, which attach to GABA receptors and act similarly to GABA. But at puberty, female mice experience a 700% increase in an unusual GABA receptor that helps calm the nervous system, except when under stress. In fact, this oddball receptor does the opposite: it responds to one of the body's stress-reducing hormones, THP, by revving up the nerves and raising anxiety.

Smith and company found that having this abundance of receptors, which recede later in adolescence, interferes with learning. And just as fascinating, a dose of THP reverses the learning deficit. "We are suggesting that mild stress is advantageous to learning in adolescence," she says. (Smith's current study involved only female mice; she plans to look next at males and females to see if there are gender differences on the learning task.)

How might this relate to humans? Actually, mild stress has been shown to improve learning in people; too much does the opposite. Smith wonders whether the discovery may help explain certain learning declines, like the drop-off in the ability to learn to speak a foreign language without an accent, which occurs sometime around puberty.

She also points to an intriguing 2002 study by San Diego State psychologist Robert McGivern that showed that certain cognitive processes become temporarily less efficient at puberty. McGivern and his associates timed 300 subjects, ages 10 to 22, as they did a very simple set of matching tasks involving pictures of facial expressions and words describing them (happy, angry, sad). The study found that around the onset of puberty (about age 11 for girls and 12 for boys), people take significantly longer to do this easy task. McGivern and his associates attributed the slow pace to the excess number of synapses in the brain at puberty — essentially, too many connections that have yet to be pruned in late adolescence.

In an interview, McGivern said he thought an apparent drop-off in the ability to learn new things at puberty might merely reflect the fact that teenagers are becoming more attuned to social issues than dull learning tasks: "It may be a shift in what we pay attention to and are motivated to look at that's driving this." But that would not explain Smith's mice or similar biochemical changes she has observed in tissue samples related to learning. (There's no question of motivation in a petri dish.)

Overall, remarkably little is known about the relationship between developing brain anatomy and observed behavior like learning. It's a young field, and Smith's "very good study raises a lot of intriguing questions," says Giedd of the NIMH.

GABA is not the only neurotransmitter system that goes out of whack at puberty, Giedd notes. Recent studies at Harvard suggest that dopamine receptors also temporarily proliferate, a change that might be related to the impulsiveness and risk-taking behaviors seen in teens. These bursts of brain changes seem to be connected to developmentally sensitive periods, says Giedd. Understanding them better just might unlock some of the enduring puzzles of adolescent behavior.