Preparing for adulthood: thousands upon thousands of new cells are born in the hippocampus during puberty, and most survive with effortful learning

The dentate gyrus of the hippocampal formation generates new granule neurons throughout life. The number of neurons produced each day is inversely related to age, with thousands more produced during puberty than during adulthood, and many fewer produced during senescence. In adulthood, approximately half of these cells undergo apoptosis shortly after they are generated. Most of these cells can be rescued from death by effortful and successful learning experiences (Gould et al., 1999; Waddell and Shors, 2008; Curlik and Shors, 2011). Once rescued, the newly-generated cells differentiate into neurons, and remain in the hippocampus for at least several months (Leuner et al., 2004). Here, we report that many new hippocampal cells also undergo cell death during puberty. Because the juvenile brain is more plastic than during adulthood, and because many experiences are new, we hypothesized that a great number of cells would be rescued by learning during puberty. Indeed, adolescent rats that successfully acquired the trace eyeblink response retained thousands more cells than animals that were not trained, and those that failed to learn. Because the hippocampus generates thousands more cells during puberty than during adulthood, these results support the idea that the adolescent brain is especially responsive to learning. This enhanced response can have significant consequences for the functional integrity of the hippocampus. Such a massive increase in cell proliferation is likely an adaptive response as the young animal must emerge from the care of its mother to face the dangers, challenges, and opportunities of adulthood.

Full Article

Flip of a single molecular switch makes an old brain young

The flip of a single molecular switch helps create the mature neuronal connections that allow the brain to bridge the gap between adolescent impressionability and adult stability. Now Yale School of Medicine researchers have reversed the process, recreating a youthful brain that facilitated both learning and healing in the adult mouse.

Scientists have long known that the young and old brains are very different. Adolescent brains are more malleable or plastic, which allows them to learn languages more quickly than adults and speeds recovery from brain injuries. The comparative rigidity of the adult brain results in part from the function of a single gene that slows the rapid change in synaptic connections between neurons.

By monitoring the synapses in living mice over weeks and months, Yale researchers have identified the key genetic switch for brain maturation a study released March 6 in the journal Neuron. The Nogo Receptor 1 gene is required to suppress high levels of plasticity in the adolescent brain and create the relatively quiescent levels of plasticity in adulthood.  In mice without this gene, juvenile levels of brain plasticity persist throughout adulthood. When researchers blocked the function of this gene in old mice, they reset the old brain to adolescent levels of plasticity.

“These are the molecules the brain needs for the transition from adolescence to adulthood,” said Dr. Stephen Strittmatter. Vincent Coates Professor of Neurology, Professor of Neurobiology and senior author of the paper. “It suggests we can turn back the clock in the adult brain and recover from trauma the way kids recover.”

Rehabilitation after brain injuries like strokes requires that patients re-learn tasks such as moving a hand. Researchers found that adult mice lacking Nogo Receptor recovered from injury as quickly as adolescent mice and mastered new, complex motor tasks more quickly than adults with the receptor.

“This raises the potential that manipulating Nogo Receptor in humans might accelerate and magnify rehabilitation after brain injuries like strokes,” said Feras Akbik, Yale doctoral student who is first author of the study.

Researchers also showed that Nogo Receptor slows loss of memories.  Mice without Nogo receptor lost stressful memories more quickly, suggesting that manipulating the receptor could help treat post-traumatic stress disorder.

“We know a lot about the early development of the brain,” Strittmatter said, “But we know amazingly little about what happens in the brain during late adolescence.”

Brain adds cells in puberty to navigate adult world

The brain adds new cells during puberty to help navigate the complex social world of adulthood, two Michigan State University neuroscientists report in the current issue of the Proceedings of the National Academy of Sciences.

Scientists used to think the brain cells you’re born with are all you get. After studies revealed the birth of new brain cells in adults, conventional wisdom held that such growth was limited to two brain regions associated with memory and smell.

But in the past few years, researchers in MSU’s neuroscience program have shown that mammalian brains also add cells during puberty in the amygdala and interconnected regions where it was thought no new growth occurred. The amygdala plays an important role in helping the brain make sense of social cues. For hamsters, it picks up signals transmitted by smell through pheromones; in humans, the amygdala evaluates facial expressions and body language.

“These regions are important for social behaviors, particularly mating behavior,” said lead author Maggie Mohr, a doctoral student in neuroscience. “So, we thought maybe cells that are added to those parts of the brain during puberty could be important for adult reproductive function.”

To test that idea, Mohr and Cheryl Sisk, MSU professor of psychology, injected male hamsters with a chemical marker to show cell birth during puberty. When the hamsters matured into adults, the researchers allowed them to interact and mate with females.

Examining the brains immediately after that rendezvous, the researchers found new cells born during puberty had been added to the amygdala and associated regions. Some of the new cells contained a protein that indicates cell activation, which told Mohr and Sisk those cells had become part of the neural networks involved in social and sexual behavior.

“Before this study it was unclear if cells born during puberty even survived into adulthood,” Mohr said. “We’ve shown that they can mature to become part of the brain circuitry that underlies adult behavior.”

Their results also showed that more of the new brain cells survived and became functional in males raised in an enriched environment – a larger cage with a running wheel, nesting materials and other features – than in those with a plain cage.

While people act in more complicated ways than rodents, the researchers said they hope their work ultimately sheds light on human behavior.

“We don’t know if cells are added to the human amygdala during puberty,” Sisk said, “but we know the amygdala plays a similar role in people as in hamsters. We hope to learn whether similar mechanisms are at play as people’s brains undergo the metamorphosis that occurs during puberty.”

Childhood trauma leaves its mark on the brain

EPFL scientists have found that childhood trauma leaves a lasting imprint on the brain – a structural change that is related to a predisposition to violence.

It is well known that violent individuals are often themselves the victims of psychological trauma experienced in childhood. Some of these individuals also exhibit alterations in their orbitofrontal cortex. But is there a connection between these physical changes in the brain and a psychologically traumatic childhood? Can one’s experiences modify the physical structure of the brain?

An EPFL team led by Professor Carmen Sandi, member of the National Centers for Competence in Research SYNAPSY, has demonstrated for the first time a correlation between psychological trauma and specific changes in the brain that are related to aggressive behavior. In rats, the experience of pre-adolescent trauma led to aggressive behavior accompanied by structural and functional changes in the brain – the same changes that have been observed in violent human beings. In other words, psychological wounds inflicted in childhood leave a lasting biological trace that persists in the adult brain. The team’s findings have been published in the January 15 edition of the journal Translational Psychiatry.

“This research shows that people exposed to trauma in childhood don’t only suffer psychologically, but their brain also gets altered,” explains Sandi, who is head of EPFL’s Laboratory of Behavioral Genetics and director of the Brain Mind Institute. “This adds an additional dimension to the consequences of abuse, and obviously has scientific, therapeutic and social implications.”

Remarkable results
The researchers were able to unravel the biological foundations of violence using a cohort of male rats that were exposed to psychologically stressful situations when young. After observing that these experiences led to aggressive behavior when the rats reached adulthood, they examined what was happening in the animals’ brains to see if the traumatic period had left a lasting mark.

“In a challenging social situation, the orbitofrontal cortex of a healthy individual is activated in order to inhibit aggressive impulses and to maintain normal interactions,” explains Sandi. “But in the rats we studied, we noticed that there was very little activation of the orbitofrontal cortex. This, in turn, reduces their ability to moderate their negative impulses. This reduced activation is accompanied by the overactivation of the amygdala, a region of the brain that’s involved in emotional reactions.” Other researchers who have studied the brains of violent human individuals have observed the same deficit in orbitofrontal activation and the same concomitant reduced inhibition of aggressive impulses. “It’s remarkable; we didn’t expect to find this level of similarity,” says Sandi.

Antidepressants and cerebral plasticity
The scientists also measured changes in the expression of certain genes in the brain. The neurobiologists focused on genes known to be involved in aggressive behavior for which there are polymorphisms (genetic variants) that predispose carriers to an aggressive attitude. They looked at whether the psychological stress experienced by the rats caused a modification in these genes’ expression. “We found that the level of MAOA gene expression increased in the prefrontal cortex,” says Sandi. This alteration was linked to an epigenetic change; in other words, the traumatic experience ended up causing a long-term modification of this gene’s expression.

Finally, the researchers tried to see if an MAOA gene inhibitor, in this case an antidepressant, could reverse the increase in aggressive behavior induced by the juvenile stress. The treatment was effective. The team will now concentrate its efforts on trying to better understand these mechanisms, and explore whether a treatment could possibly reverse these changes in the brain, and above all, to shed light on whether some people are more vulnerable than others depending on their genetic makeup. “This research could also reveal the possible ability of antidepressants – an ability that’s increasingly being suspected – to renew cerebral plasticity,” says the professor.

Scientists identify depression and anxiety biomarker in youths

Scientists have discovered a cognitive biomarker – a biological indicator of a disease – for young adolescents who are at high risk of developing depression and anxiety. Their findings were published in the journal PLOS ONE.

The test for the unique cognitive biomarker, which can be done on a computer, could be used as an inexpensive tool to screen adolescents for common emotional mental illnesses.  As the cognitive biomarker may appear prior to the symptoms of depression and anxiety, early intervention (which has proven to be one of the most effective ways of combatting mental illness) could then be initiated.

For the study, 15-18 year old participants underwent genetic testing and environmental assessment, an exercise which would currently be too expensive and take too long to use as a widespread method of screening.  The adolescents were then given a computer test to gauge how they process emotional information. The test had the participants evaluate whether words were positive, negative or neutral (examples included ‘joyful’ for positive, ‘failure’ for negative, and ‘range’ for neutral).

Those adolescents with a variation of one gene (the short form of the serotonin transporter) as well as exposure to intermittent family arguments for longer than six months and violence between parents before the age of six were shown to have marked difficulty in evaluating the emotion within the words, indicating an inability to process emotional information. Previous research associated a maladjusted perception and response to emotions, as seen here, with a significantly increased risk of depression and anxiety.

Professor Ian Goodyer, Principal Investigator on the study from the University of Cambridge, said:  “Whether we succumb to anxiety and depression depends in part on our tendencies to think well or poorly of ourselves at troubled times. How it comes about that some people see the ‘glass half full’ and think positively whereas other see the ‘glass half empty’ and think negatively about themselves at times of stress is not known.

The evidence is that both our genes and our early childhood experiences contribute to such personal thinking styles. Before there are any clinical symptoms of depression or anxiety, this test reveals a deficient ability to efficiently and effectively perceive emotion processes in some teenagers – a biomarker for low resilience which may lead to mental illnesses.”

"Blue" Light Could Help Teenagers Combat Stress

Adolescents can be chronically sleep deprived because of their inability to fall asleep early in combination with fixed wakeup times on school days. According to the CDC, almost 70 percent of school children get insufficient sleep—less than 8 hours on school nights. This type of restricted sleep schedule has been linked with depression, behavior problems, poor performance at school, drug use, and automobile accidents. A new study from the Lighting Research Center (LRC) at Rensselaer Polytechnic Institute shows that exposure to morning short-wavelength “blue” light has the potential to help sleep-deprived adolescents prepare for the challenges of the day and deal with stress, more so than dim light.

The study was a collaboration between Associate Professor and Director of the LRC Light and Health Program Mariana Figueiro and LRC Director and Professor Mark S. Rea. Results of the study titled “Short-Wavelength Light Enhances Cortisol Awakening Response in Sleep-Restricted Adolescents,” were recently published in the open access International Journal of Endocrinology. The full text is available at http://www.hindawi.com/journals/ije/2012/301935/.

(Image credit)

Delayed Development: 20-Somethings Blame the Brain

Recent research into how the brain develops suggests that people are better equipped to make major life decisions in their late 20s than earlier in the decade. The brain, once thought to be fully grown after puberty, is still evolving into its adult shape well into a person’s third decade, pruning away unused connections and strengthening those that remain, scientists say.

"Until very recently, we had to make some pretty important life decisions about education and career paths, who to marry and whether to go into the military at a time when parts of our brains weren’t optimal yet," says neuroscientist Jay Giedd at the National Institute of Mental Health, whose brain-imaging studies of thousands of young people have yielded many of the new insights. Postponing those decisions makes sense biologically, he says. "It’s a good thing that the 20s are becoming a time for self-discovery."

Such findings are part of a new wave of research into “emerging adulthood,” the years roughly from 18 to 29, which psychologists, sociologists and neuroscientists increasingly see as a distinct life stage. The gap between adolescence and full adulthood is becoming ever wider as more young people willingly or because of economic necessity prolong their education and postpone traditional adult responsibilities. As recently as the 1960s, the average age of first marriage for women in the U.S. was 20, and men 22. Today, the average is 26 for women and 28 for men.

Read more