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.”

Response and recovery in the brain may predict well-being

It has long been known that the part of the brain called the amygdala is responsible for recognition of a threat and knowing whether to fight or flee from the danger.

Now, using functional magnetic resonance imaging, or fMRI, scientists at the Center for Investigating Healthy Minds at the University of Wisconsin-Madison Waisman Center are watching the duration of the amygdala response in the brains of healthy people when exposed to negative images. How long the recovery takes may be an indicator of personality traits like neuroticism.

Recently published in the journal Social Cognitive and Affective Neuroscience, the study specifically examines how the amygdala responds and recovers from negative stimuli. One of the more primitive parts of the mammalian brain, the amygdala is central to processing emotion, including activating changes in the body that often accompany emotion. In terms of its evolutionary function, this region of the brain is part of a circuit that is key to our sense of fear recognition and alertness to danger.

While the role of the amygdala has been understood and well documented, the time course for the response-recovery process has never been investigated, nor observed, until the recent advance of fMRI analysis methods.

"Past studies looking at the temporal unfolding of emotional responses have focused on reports of emotional experience obtained from interviews and questionnaires," says Tammi Kral, research specialist at the Center for Investigating Healthy Minds and an author of the paper. "This study is different because it looks at the temporal activity in the brain via fMRI."

Through the lens of fMRI, scientists can measure the activation in the amygdala as it reacts to negative stimuli, and the subsequent recovery after the stimulus ends. This study shows that while the initial reactivity of the amygdala does not predict personality traits, a sluggish response-recovery time may be a predictor of neuroticism.

"People’s responses to negative emotional stimuli, and their ability to regulate those responses, can be a major factor in depression, anxiety and other psychological disorders," says Kral. "In the case of depression, the person is often ruminating, perseverating — they’re unable to let go of the negative experience."

The study could have clinical applications because it implies that changing the way people recover from negative occurrences may be a good way to improve their emotional well-being. Research from other groups also supports the idea that individual differences in emotional recovery affect overall well-being.

Human brain is divided on fear and panic

When doctors at the University of Iowa prepared a patient to inhale a panic-inducing dose of carbon dioxide, she was fearless. But within seconds of breathing in the mixture, she cried for help, overwhelmed by the sensation that she was suffocating.

The patient, a woman in her 40s known as SM, has an extremely rare condition called Urbach-Wiethe disease that has caused extensive damage to the amygdala, an almond-shaped area in the brain long known for its role in fear. She had not felt terror since getting the disease when she was an adolescent.

In a paper published online Feb. 3 in the journal Nature Neuroscience, the UI team provides proof that the amygdala is not the only gatekeeper of fear in the human mind. Other regions—such as the brainstem, diencephalon, or insular cortex—could sense the body’s most primal inner signals of danger when basic survival is threatened.

“This research says panic, or intense fear, is induced somewhere outside of the amygdala,” says John Wemmie, associate professor of psychiatry at the UI and senior author on the paper. “This could be a fundamental part of explaining why people have panic attacks.”

If true, the newly discovered pathways could become targets for treating panic attacks, post-traumatic stress syndrome, and other anxiety-related conditions caused by a swirl of internal emotional triggers.

“Our findings can shed light on how a normal response can lead to a disorder, and also on potential treatment mechanisms,” says Daniel Tranel, professor of neurology and psychology at the UI and a corresponding author on the paper.

Even the brains of people with anxiety states can get used to fear

Fear is a protective function against possible dangers that is designed to save our lives. Where there are problems with this fear mechanism, its positive effects are cancelled out: patients who have a social phobia become afraid of perfectly normal, everyday social situations because they are worried about behaving inappropriately or being thought of as stupid by other people. Scientists from the Centre for Medical Physics and Biomedical Technology and the University Department of Psychiatry and Psychotherapy at the MedUni Vienna have now discovered that this fear circuit can be deactivated, at least in part.

In a study by Ronald Sladky, led by Christian Windischberger (Centre for Medical Physics and Biomedical Technology), which has recently been published in the magazine PLOS One, functional magnetic resonance tomography was used to measure the changes in the brain activity of socially phobic patients and healthy test subjects while they were looking at faces. This experiment simulates social confrontation with other people without actually placing the individual in an intolerable situation of anxiety.

Permanent confrontation has a diminishing effect on anxiety
“The study demonstrated that people with social phobia initially exhibit greater activity in the amygdala and in the medial, prefrontal cortex of the brain, however after a few faces this activity recedes,” says Sladky. This contradicts the assumption made thus far that the emotional circuit of socially phobic individuals is unable to adapt adequately to this stress-inducing situation.

Permanent confrontation with the test task not only led to a solution to the “problem” being found more quickly among the patients with anxiety, but also to some areas of the brain being bypassed which otherwise were over-stimulated, a characteristic typical of anxiety. Says Sladky: “We therefore concluded that there are functional control strategies even in the emotional circuits of people with social phobia, although the mechanisms take longer to take effect in these individuals. The misregulation of these parts of the brain can therefore be compensated to a degree.”

These findings could, according to Sladky, provide a starting point for the development of personalised training programmes that will help affected individuals to conquer unpleasant situations in their everyday lives more effectively. In Austria, around 200,000 people a year are affected by some form of social phobia. The number of people who suffer this condition without seeking help for it is likely to be very high, since many affected individuals fail to seek assistance or do so only too late as a result of their anxiety.

Scientists Uncover a Previously Unknown Mechanism of Memory Formation

It takes a lot to make a memory. New proteins have to be synthesized, neuron structures altered. While some of these memory-building mechanisms are known, many are not. Some recent studies have indicated that a unique group of molecules called microRNAs, known to control production of proteins in cells, may play a far more important role in memory formation than previously thought.

Now, a new study by scientists on the Florida campus of The Scripps Research Institute has for the first time confirmed a critical role for microRNAs in the development of memory in the part of the brain called the amygdala, which is involved in emotional memory. The new study found that a specific microRNA—miR-182—was deeply involved in memory formation within this brain structure.

“No one had looked at the role of microRNAs in amygdala memory,” said Courtney Miller, a TSRI assistant professor who led the study. “And it looks as though miR-182 may be promoting local protein synthesis, helping to support the synapse-specificity of memories.”

In the new study, published in the Journal of Neuroscience, the scientists measured the levels of all known microRNAs following an animal model of learning. A microarray analysis, which enables rapid genetic testing on a large scale, showed that more than half of all known microRNAs are expressed in the amygdala. Seven of those microRNAs increased and 32 decreased when learning occurred.

The study found that, of the microRNAs expressed in the brain, miR-182 had one of the lowest levels and these decreased further with learning. Despite these very low levels, its overexpression prevented the formation of memory and led to a decrease in proteins that regulate neuronal plasticity (neurons’ ability to adapt) through changes in structure.

These findings suggest that learning-induced suppression of miR-182 is a main supporting factor in the formation of long-term memory in the amagdala, as well as an underappreciated mechanism for regulating protein synthesis during memory consolidation, Miller said.

Further analysis identified miR-182 as a repressor of proteins that control actin—a major component of the cytoskeleton, the scaffolding that holds cells together.

“We know that memory formation requires changes in dendritic spines on the neurons through regulation of the actin cytoskeleton,” Miller said. “When miR-182 is suppressed through learning it halts, at least in part, repression of actin-regulating proteins, so there’s a good chance that miR-182 exerts important control over the actin cytoskeleton.”

Miller is now interested in whether or not high levels of miR-182 accumulate in the aging brain, something that would help to explain a tendency toward memory loss in the elderly. She also notes that other research has shown that animal models lacking miR-182 had no significant physical or cellular abnormalities, suggesting that miR-182 could be a viable target for drug discovery.

(Image: stockfresh)

Neuroscientists pinpoint location of fear memory in amygdala

A rustle of undergrowth in the outback: it’s a sound that might make an animal or person stop sharply and be still, in the anticipation of a predator. That “freezing” is part of the fear response, a reaction to a stimulus in the environment and part of the brain’s determination of whether to be afraid of it.

A neuroscience group at Cold Spring Harbor Laboratory (CSHL) led by Assistant Professor Bo Li Ph.D., together with collaborator Professor Z. Josh Huang Ph.D., today release the results of a new study that examines the how fear responses are learned, controlled, and memorized. They show that a particular class of neurons in a subdivision of the amygdala plays an active role in these processes.

Locating fear memory in the amygdala

Previous research had indicated that structures inside the amygdalae, a pair of almond-shaped formations that sit deep within the brain and are known to be involved in emotion and reward-based behavior, may be part of the circuit that controls fear learning and memory. In particular, a region called the central amygdala, or CeA, was thought to be a passive relay for the signals relayed within this circuit.

Li’s lab became interested when they observed that neurons in a region of the central amygdala called the lateral subdivision, or CeL, “lit up” in a particular strain of mice while studying this circuit.

“Neuroscientists believed that changes in the strength of the connections onto neurons in the central amygdala must occur for fear memory to be encoded,” Li says, “but nobody had been able to actually show this.”

This led the team to further probe into the role of these neurons in fear responses and furthermore to ask the question: If the central amygdala stores fear memory, how is that memory trace read out and translated into fear responses?

To examine the behavior of mice undergoing a fear test the team first trained them to respond in a Pavlovian manner to an auditory cue. The mice began to “freeze,” a very common fear response, whenever they heard one of the sounds they had been trained to fear.

To study the particular neurons involved, and to understand them in relation to the fear-inducing auditory cue, the CSHL team used a variety of methods. One of these involved delivering a gene that encodes for a light-sensitive protein into the particular neurons Li’s group wanted to look at.

By implanting a very thin fiber-optic cable directly into the area containing the photosensitive neurons, the team was able to shine colored laser light with pinpoint accuracy onto the cells, and in this manner activate them. This is a technique known as optogenetics. Any changes in the behavior of the mice in response to the laser were then monitored.

A subset of neurons in the central amygdala controls fear expression

The ability to probe genetically defined groups of neurons was vital because there are two sets of neurons important in fear-learning and memory processes. The difference between them, the team learned, was in their release of message-carrying neurotransmitters into the spaces called synapses between neurons. In one subset of neurons, neurotransmitter release was enhanced; in another it was diminished. If measurements had been taken across the total cell population in the central amygdala, neurotransmitter levels from these two distinct sets of neurons would have been averaged out, and thus would not have been detected.

Li’s group found that fear conditioning induced experience-dependent changes in the release of neurotransmitters in excitatory synapses that connect with inhibitory neurons – neurons that suppress the activity of other neurons – in the central amygdala. These changes in the strength of neuronal connections are known as synaptic plasticity.

Particularly important in this process, the team discovered, were somatostatin-positive (SOM+) neurons. Somatostatin is a hormone that affects neurotransmitter release. Li and colleagues found that fear-memory formation was impaired when they prevent the activation of SOM+ neurons.

SOM+ neurons are necessary for recall of fear memories, the team also found. Indeed, the activity of these neurons alone proved sufficient to drive fear responses. Thus, instead of being a passive relay for the signals driving fear learning and responses in mice, the team’s work demonstrates that the central amygdala is an active component, and is driven by input from the lateral amygdala, to which it is connected.

“We find that the fear memory in the central amygdala can modify the circuit in a way that translates into action — or what we call the fear response,” explains Li.

In the future Li’s group will try to obtain a better understanding of how these processes may be altered in post-traumatic stress disorder (PTSD) and other disorders involving abnormal fear learning. One important goal is to develop pharmacological interventions for such disorders.

Li says more research is needed, but is hopeful that with the discovery of specific cellular markers and techniques such as optogenetics, a breakthrough can be made.

Deep brain stimulation improves autistic boy’s symptoms

Electrodes implanted deep in the brain of a boy with severe autism have enabled him to live a more normal life. The treatment reduced his destructive behavior and allowed the formerly nonverbal boy to speak a few words, scientists report online January 21 in Frontiers in Human Neuroscience.

The results are the first to use brain stimulation to alleviate symptoms of autism. Scientists caution that interpreting the results broadly is impossible without larger, systematic studies, but even so neurosurgeon Ali Rezai of the Ohio State University Wexner Medical Center in Columbus calls the boys’ gains “intriguing and promising.”

The boy in the study, who was 13 at the time of his experimental surgery, suffered from severe autism symptoms: He couldn’t talk or make eye contact, woke up screaming repeatedly during the night, and habitually injured himself so badly that his parents restrained him almost constantly to protect him. Multiple rounds of psychiatric drugs failed to stave off his worsening symptoms.

In an effort to help him, doctors led by Volker Sturm of the University Hospital of Cologne in Germany implanted electrodes into the boy’s brain. Through trial and error, the doctors realized that stimulating a part of the amygdala, a brain structure important for emotions and memory, improved the boy’s symptoms. Stimulating other brain areas had no effect or worsened his symptoms.

After eight weeks of continuous electrical stimulation, the boy shifted on a clinical scale that measures irritability from “severely ill” to “moderately ill.” The boy also improved on a scale that measures autism symptoms. He began to make eye contact and was better able to control his behavior.

Brain region associated with selfishness

People with damage to a specific part of the brain entrusted unexpectedly large amounts of money to complete strangers. In an investment game played in the lab, three women with damage to a small part of the brain called the basolateral amygdala handed over nearly twice as much money as healthy people.

These women didn’t expect to make a bunch of money back, an international team of researchers reports online the week of January 21 in the Proceedings of the National Academy of Sciences. Nor did they think the person they invested with was particularly trustworthy. When asked why they would invest so generously, the volunteers couldn’t provide an answer.

The results suggest that normally, the basolateral amygdala enables selfishness — putting the squeeze on generosity.

(Image credit)

Postpartum women less stressed by threats unrelated to the baby

Following the birth of a child, new mothers may have an altered perception of stresses around them, showing less interest in threats unrelated to the baby. This change to the neuroendocrine circuitry could help the mothers adapt to the additional stress often accompanying newborns, say researchers from Indiana University’s Kinsey Institute and the University of Zurich.

When viewing disturbing images during the study, postpartum women reported less distress and demonstrated less activity in their amygdala, the part of the brain that controls emotional response, than nulliparous, or childless, women, according to functional magnetic resonance imaging.

When the childless women were administered a nasal spray containing the hormone oxytocin, however, their brain images looked more similar to the postpartum women, and they also reported less subjective stress when viewing the images.

"Our findings extend previous work showing a lower stress response with motherhood that likely enhances her ability to cope with this dramatic new role," said lead author Heather Rupp, director of psychology and neuroscience at Brain Surgery Worldwide Inc. and a research fellow at The Kinsey Institute for Research in Sex, Gender and Reproduction.

The study, “Amygdala response to negative images in postpartum verses nulliparous women and intranasal oxytocin,” was published in the online journal Social Cognitive and Affective Neuroscience.