Archive for the ‘Neuron’ Category



















Everyone knows it’s easier to learn about a topic you’re curious about. Now, a new study reveals what’s going on in the brain during that process, revealing that such curiosity may give a person a memory boost.

When participants in the study were feeling curious, they were better at remembering information even about unrelated topics, and brain scans showed activity in areas linked to reward and memory.

The results, detailed October 2 in the journal Neuron, hint at ways to improve learning and memory in both healthy people and those with neurological disorders, the researchers said.

“Curiosity may put the brain in a state that allows it to learn and retain any kind of information, like a vortex that sucks in what you are motivated to learn, and also everything around it,” Matthias Gruber, a memory researcher at the University of California, Davis, said in a statement. “These findings suggest ways to enhance learning in the classroom and other settings.”

Gruber and his colleagues put people in a magnetic resonance imaging (MRI) scanner and showed them a series of trivia questions, asking them to rate their curiosity about the answers to those questions. Later, the participants were shown selected trivia questions, then a picture of a neutral face during a 14-second delay, followed by the answer. Afterward, the participants were given a surprise memory test of the faces, and then a memory test of the trivia answers.

Not surprisingly, the study researchers found that people remembered more information about the trivia when they were curious about the trivia answers. But unexpectedly, when the participants were curious, they were also better at remembering the faces, an entirely unrelated task. Participants who were curious were also more likley than others to remember both the trivia information and unrelated faces a day later, the researchers found.

The brain scans showed that, compared with when their curiosity wasn’t piqued, when people were curious, they showed more activation of brain circuits in the nucleus accumbens, an area involved in reward. These same circuits, mediated by the neurochemical messenger dopamine, are involved in forms of external motivation, such as food, sex or drug addiction.

Finally, being curious while learning seemed to produce a spike of activity in the hippocampus, an area involved in forming new memories, and strengthened the link between memory and reward brain circuits.

The study’s findings not only highlight the importance of curiosity for learning in healthy people, but could also give insight into neurological conditions. For example, as people age, their dopamine circuits tend to deteriorate, so understanding how curiosity affects these circuits could help scientists develop treatments for patients with memory disorders, the researchers said.

By Elizabeth Norton

Cultures around the world have long assumed that women are hardwired to be mothers. But a new study suggests that caring for children awakens a parenting network in the brain—even turning on some of the same circuits in men as it does in women. The research implies that the neural underpinnings of the so-called maternal instinct aren’t unique to women, or activated solely by hormones, but can be developed by anyone who chooses to be a parent.

“This is the first study to look at the way dads’ brains change with child care experience,” says Kevin Pelphrey, a neuroscientist at Yale University who was not involved with the study. “What we thought of as a purely maternal circuit can also be turned on just by being a parent—which is neat, given the way our culture is changing with respect to shared responsibility and marriage equality.”

The findings come from an investigation of two types of households in Israel: traditional families consisting of a biological mother and father, in which the mother assumed most of the caregiving duties, though the fathers were very involved; and homosexual male couples, one of whom was the biological father, who’d had the child with the help of surrogate mothers. The two-father couples had taken the babies home shortly after birth and shared caregiving responsibilities equally. All participants in the study were first-time parents.

Researchers led by Ruth Feldman, a psychologist and neuroscientist at Bar-Ilan University in Ramat Gan, Israel, visited with the families in their homes, videotaping each parent with the child and then the parents and children alone. The team, which included collaborators at the Tel Aviv Sourasky Medical Center in Israel, also took saliva samples from all parents before and after the videotaped sessions to measure oxytocin—a hormone that’s released at times of intimacy and affection and is widely considered the “trust hormone.” Within a week of the home visit, the participants underwent functional magnetic resonance imaging scanning to determine how their brains reacted to the videotapes of themselves with their infants.

The mothers, their husbands, and the homosexual father-father couples all showed the activation of what the researchers term a “parenting network” that incorporated two linked but separate pathways in the brain. One circuit encompasses evolutionarily ancient structures such as the amygdala, insula, and nucleus accumbens, which handle strong emotions, attention, vigilance, and reward. The other pathway turns up in response to learning and experience and includes parts of the prefrontal cortex and an area called the superior temporal sulcus.

In the mothers, activation was stronger in the amygdala-centered network, whereas the heterosexual fathers showed more activity in the network that’s more experience-dependent. At first glance, Feldman says, the finding would seem to suggest that mothers are more wired up to nurture, protect, and possibly worry about their children. The fathers, in contrast, might have to develop these traits through tending, communicating, and learning from their babies what various sounds mean and what the child needs.

“It’s as if the father’s amygdala can shut off when there’s a woman around,” Feldman observes. It could be assumed, she says, that this circuitry is activated only by the rush of hormones during conception, pregnancy, and childbirth.

But the brains of the homosexual couples, in which each partner was a primary caregiver, told a different story. All of these men showed activity that mirrored that of the mothers, with much higher activation in the amygdala-based network, the team reports online today in the Proceedings of the National Academy of Sciences.

This finding argues strongly that the experience of hands-on parenting, with no female mother anywhere in the picture, can configure a caregiver’s brain in the same way that pregnancy and childbirth do, Feldman says.

She adds that in the heterosexual fathers, the activation of the amygdala-based network was proportional to the amount of time they spent with the baby, though the activity wasn’t as high as in the mothers or in the two-father couples.

Feldman does not believe that the brain activity of the primary-caregiving fathers differed because they were gay. Previous imaging studies, she notes, show no difference in brain activation when homosexual and heterosexual participants viewed pictures of their loved ones.

Future studies, Pelphrey says, might focus more closely on this question. “But it’s clear that we’re all born with the circuitry to help us be sensitive caregivers, and the network can be turned up through parenting.”

The mechanisms that drive axon regeneration after central nervous system (CNS) injury or disease are proposed to recapitulate, at least in part, the developmental axon growth pathways. This hypothesis is bolstered by a new study by O’Donovan et al. showing that activation of a B-RAF kinase signaling pathway is sufficient to promote robust axon growth not only during development but also after injury.

B-RAF was previously shown to be essential for developmental axon growth but it was not known if additional signaling pathways are required. In this study, the authors demonstrate that activation of B-RAF alone is sufficient to promote sensory axon growth during development. Using a conditional B-RAF gain-of-function mouse model, the authors elegantly prove that B-RAF has a cell-autonomous role in the developmental axon growth program. Notably, activated B-RAF promoted overgrowth of embryonic sensory axons projecting centrally in the spinal cord, suggesting that this pathway may normally be quiescent in central axons.

Could activated B-RAF also enhance axon regeneration in the adult central nervous system? The authors found that activated B-RAF not only enabled sensory axon growth into the spinal cord after spinal injury, but also promoted regrowth of axons projecting in the optic nerve. Regeneration in the injured CNS is prevented by both the poor intrinsic regrowth capacity of axons and by inhibitory factors in the tissue environment. Importantly, the B-RAF–activated signaling growth program was insensitive to this repulsive environment.

Interestingly, the authors find that B-RAF synergizes with the PI3-kinase–mTOR pathway, which also functions downstream of growth factors. This opens the possibility that combinatorial approaches that integrate these two pathways may heighten regenerative capacity.

This in vivo study significantly advances the understanding of the role of MAP kinases in axon growth and suggests that reactivation of the B-RAF pathway may be exploited to promote axon regeneration in the injured central nervous system. An exciting future avenue will be to determine the downstream mechanisms controlled by B-RAF.

O’Donovan, K.J., et al. 2014. J. Exp. Med. doi:10.1084/jem.20131780.

Sol Snyder, Distinguished Service Professor of Neuroscience, Pharmacology and Psychiatry, School of Medicine

Growing up, I never had any strong interest in science. I did well in lots of things in high school. I liked reading philosophy and things like that, but being a philosopher is not a fit job for a nice Jewish boy.

This was in the mid-1950s, and many of my friends were going into engineering, preparatory to joining the then prominent military industrial complex. Others were going to be doctors, so I got the idea that maybe I’d be a psychiatrist. I didn’t have any special affinity for medicine or desire to cast out the lepers or heal mankind.

I was always reading things. My father valued education. He wasn’t a big advice giver, but he … had a lot of integrity. What was important to him was doing the right thing. And he had great respect for the intellectual life and science.

My father’s professional life commenced in 1935 as the 10th employee of what became the NSA. He led a team that broke one of the principal Japanese codes. At the end of World War II, computers were invented, and, if you think about it, what could be the best entity to take advantage of computers than NSA, with its mission of sorting gibberish and looking for patterns. So my father was assigned to look at these new machines and see if they would be helpful. He led the computer installations at NSA.

Summers in college I worked in the NSA. My father taught me to program computers in machine language. Computers were a big influence on me.

I learned at the NSA about keeping secrets. What is top secret, what is need-to-know—that is one of the things you learn in the business. You don’t talk to the guy at the next desk even if you’re working on the same project. If that person doesn’t need to know, you just shut up.

In medical school, I started working at the NIH in Bethesda during the summers and elective periods, largely because the only thing I really did well up to that time was play the classical guitar and one of my guitar students was an NIH researcher. In high school I thought I might go the conservatory route, but that’s even less fitting for a nice Jewish boy than being a philosopher.

It was through my contacts at NIH that I was able to get a position working with future Nobel Prize winner Julius Axelrod. Julie was a wonderful mentor who did research on drugs and neurotransmitters. Working with him was inspirational. I just adored it.

What was notable about Julie was his great creativity, always coming up with original ideas. Even though he was an eminent scientist, he didn’t have a regular office. He just had a desk in a lab. He did experiments with his own two hands every day.

Philosophically, Julie emphasized you go where the data takes you. Don’t worry that you’re an expert in enzyme X and so should focus on that. If the data point to enzyme Y, go for it. Do what’s exciting.

My very first project with Julie was studying the disposition of histamine. I thought I had found that histamine had been converted into a novel product that looked really interesting, and I was wrong. I missed the true product because we separated the chemicals on paper and discarded the radioactivity at the bottom, throwing away the real McCoy. Another lab at Yale found it, led, remarkably, by a close friend since kindergarten. My humiliation didn’t last very long. I learned not to be so sloppy, to take greater care, and, most important, to explore peculiar results.

How does one pick research directions? You can go where it’s “hot,” but there you’re competing with 300 other people, and everyone can make only incremental changes. But if you follow Julie Axelrod’s rules and you don’t worry about what’s hot, or what other people are doing—just go where your data are taking you—then you have a better chance of finding something that nobody else had found before.

With the discovery of the opiate receptor, I was fortunate to launch a new field: molecular identification of neurotransmitter receptors. Later we discovered that the gas nitrous oxide is a neurotransmitter.

I’m a klutz. I can’t hammer a nail. So for the technical side, like dissecting brains to look at different regions, I enlisted friends. I learned to collaborate, a key element in so many discoveries.

Johns Hopkins has always been a collegial place. People are just friendly and interact with each other. This tradition goes back to the founding of the medical school, permeating the school’s governance as well as research. We tend to be more productive than faculty at other schools, where one gets ahead by sticking an ice pick in the backs of colleagues.

One of my heroes was my guitar teacher, Sophocles Papas, Andrés Segovia’s best friend. Sophocles was an important influence in my life, and we stayed close until he died in his 90s. In a couple of years after commencing lessons, I was giving recitals, all thanks to him. Like Julie, Sophocles emphasized innovative short cuts to creativity.

I’ve remained involved with music. I’m the longest-serving trustee on the Baltimore Symphony Orchestra, chairing for many years its music committee. Trustees of arts organizations are typically businesspeople selected for their fundraising acumen. But the person who nominated me reportedly commented, I’d like to propose something radical: I’d like to propose a trustee who cares about music.

Most notable about psychiatry is that the major drugs—antipsychotics for schizophrenia, antidepressants, and anti-anxiety drugs—were all discovered in the mid-1950s. Subsequent tweaking has enhanced potency and diminished side effects, but there have been no major breakthroughs. No new class of drugs since 1958—rather frustrating.

As biomedical science advances, especially with the dawn of molecular biology, our power to innovate is just dazzling. Today’s students take all of this for granted, but those of us who have been doing research for several decades are daily amazed by our abilities to probe the mysteries of life.

The logic of nature is elegant and straightforward. The more we learn about how the body works, the more we are amazed by its beauty and inherent simplicity.

One of my pet peeves is that the very power of modern science leads journal and grant reviewers to expect every “i” dotted and every “t” crossed. Because of this, four years or more of work go into each scientific manuscript. Then, editors and reviewers of journals are so picayune that revising a paper consumes another year.

Now let’s consider the poor post­doctoral fellow or graduate student. To move forward in his or her career requires at least one major publication—a five-year enterprise. If you only have one shot on goal, one paper in five years, your chances of success shrivel. The duration of PhD training and postdoctoral training is getting so long that from the entry point at graduate school to the time you’re out looking for a job as an assistant professor is easily 12, 15 years. Well, that is ridiculous. If you got paid $10 million at the end of this road, that would be one thing, but scientists earn less than most other professionals. We’re deterring the young smart people from going into science.

Biomedical researchers don’t work in a vacuum. They work with grad students and postdoctoral fellows, so being a good mentor is key to being a good scientist. Keep your students well motivated and happy. Have them feel that they are good human beings, and they will do better science.

The most important thing is that you value the integrity of each person. I ask my students all the time, What do you think? And this discussion turns into minor league psychotherapy. Ah, you think that? Tell me more. Tell me more.

The “stupidest” of the students here are smarter than me. It’s a pleasure to watch them emerge.

I see my life as taking care of other people. Although I didn’t go to medical school with any intelligent motivation, once I did, I loved being a doctor and trying to help people. And I love being a psychiatrist and trying to understand people, and I try to carry that into everything I do.

In medical research, all of us want to find the causes and cures for diseases. I haven’t found the cause of any disease, although with Huntington’s disease, we are making inroads. And, of course, being a pharmacologist, my métier is discovering drugs and better treatments.

My secret? I come to work every day, and I keep my own calendar. That way I have free time to just wander around the lab and talk to the boys and girls and ask them how it’s going. That’s what makes me happy.

Sol Snyder joined Johns Hopkins in 1965 as an assistant resident in Psychiatry and would later become the youngest full professor in JHU history. In 1978, he received the Albert Lasker Basic Medical Research Award for his role in discovering the brain’s opiate receptors. In 1980, he founded the School of Medicine’s Department of Neuroscience, which in 2006 was renamed the Solomon H. Snyder Department of Neuroscience.


Roaming bits of DNA that can relocate and proliferate throughout the genome, called “jumping genes,” may contribute to schizophrenia, a new study suggests. These rogue genetic elements pepper the brain tissue of deceased people with the disorder and multiply in response to stressful events, such as infection during pregnancy, which increase the risk of the disease. The study could help explain how genes and environment work together to produce the complex disorder and may even point to ways of lowering the risk of the disease, researchers say.

Schizophrenia causes hallucinations, delusions, and a host of other cognitive problems, and afflicts roughly 1% of all people. It runs in families—a person whose twin sibling has the disorder, for example, has a roughly 50-50 chance of developing it. Scientists have struggled to define which genes are most important to developing the disease, however; each individual gene associated with the disorder confers only modest risk. Environmental factors such as viral infections before birth have also been shown to increase risk of developing schizophrenia, but how and whether these exposures work together with genes to skew brain development and produce the disease is still unclear, says Tadafumi Kato, a neuroscientist at the RIKEN Brain Science Institute in Wako City, Japan and co-author of the new study.

Over the past several years, a new mechanism for genetic mutation has attracted considerable interest from researchers studying neurological disorders, Kato says. Informally called jumping genes, these bits of DNA can replicate and insert themselves into other regions of the genome, where they either lie silent, doing nothing; start churning out their own genetic products; or alter the activity of their neighboring genes. If that sounds potentially dangerous, it is: Such genes are often the culprits behind tumor-causing mutations and have been implicated in several neurological diseases. However, jumping genes also make up nearly half the current human genome, suggesting that humans owe much of our identity to their audacious leaps.

Recent research by neuroscientist Fred Gage and colleagues at the University of California (UC), San Diego, has shown that one of the most common types of jumping gene in people, called L1, is particularly abundant in human stem cells in the brain that ultimately differentiate into neurons and plays an important role in regulating neuronal development and proliferation. Although Gage and colleagues have found that increased L1 is associated with mental disorders such as Rett syndrome, a form of autism, and a neurological motor disease called Louis-Bar syndrome, “no one had looked very carefully” to see if the gene might also contribute to schizophrenia, he says.

To investigate that question, principal investigator Kazuya Iwamoto, a neuroscientist; Kato; and their team at RIKEN extracted brain tissue of deceased people who had been diagnosed with schizophrenia as well as several other mental disorders, extracted DNA from their neurons, and compared it with that of healthy people. Compared with controls, there was a 1.1-fold increase in L1 in the tissue of people with schizophrenia, as well as slightly less elevated levels in people with other mental disorders such as major depression, the team reports today in Neuron.

Next, the scientists tested whether environmental factors associated with schizophrenia could trigger a comparable increase in L1. They injected pregnant mice with a chemical that simulates viral infection and found that their offspring did, indeed, show higher levels of the gene in their brain tissue. An additional study in infant macaques, which mimicked exposure to a hormone also associated with increased schizophrenia risk, produced similar results. Finally, the group examined human neural stem cells extracted from people with schizophrenia and found that these, too, showed higher levels of L1.

The fact that it is possible to increase the number of copies of L1 in the mouse and macaque brains using established environmental triggers for schizophrenia shows that such genetic mutations in the brain may be preventable if such exposures can be avoided, Kato says. He says he hopes that the “new view” that environmental factors can trigger or deter genetic changes involved in the disease will help remove some of the disorder’s stigma.

Combined with previous studies on other disorders, the new study suggests that L1 genes are indeed more active in the brain of patients with neuropsychiatric diseases, Gage says. He cautions, however, that no one yet knows whether they are actually causing the disease. “Now that we have multiple confirmations of this occurring in humans with different diseases, the next step is to determine if possible what role, if any, they play.”

One tantalizing possibility is that as these restless bits of DNA drift throughout the genomes of human brain cells, they help create the vibrant cognitive diversity that helps humans as a species respond to changing environmental conditions, and produces extraordinary “outliers,” including innovators and geniuses such as Picasso, says UC San Diego neuroscientist Alysson Muotri. The price of such rich diversity may be that mutations contributing to mental disorders such as schizophrenia sometimes emerge. Figuring out what these jumping genes truly do in the human brain is the “next frontier” for understanding complex mental disorders, he says. “This is only the tip of the iceberg.”


Doctors in the US have induced feelings of intense determination in two men by stimulating a part of their brains with gentle electric currents.

The men were having a routine procedure to locate regions in their brains that caused epileptic seizures when they felt their heart rates rise, a sense of foreboding, and an overwhelming desire to persevere against a looming hardship.

The remarkable findings could help researchers develop treatments for depression and other disorders where people are debilitated by a lack of motivation.

One patient said the feeling was like driving a car into a raging storm. When his brain was stimulated, he sensed a shaking in his chest and a surge in his pulse. In six trials, he felt the same sensations time and again.

Comparing the feelings to a frantic drive towards a storm, the patient said: “You’re only halfway there and you have no other way to turn around and go back, you have to keep going forward.”

When asked by doctors to elaborate on whether the feeling was good or bad, he said: “It was more of a positive thing, like push harder, push harder, push harder to try and get through this.”

A second patient had similar feelings when his brain was stimulated in the same region, called the anterior midcingulate cortex (aMCC). He felt worried that something terrible was about to happen, but knew he had to fight and not give up, according to a case study in the journal Neuron.

Both men were having an exploratory procedure to find the focal point in their brains that caused them to suffer epileptic fits. In the procedure, doctors sink fine electrodes deep into different parts of the brain and stimulate them with tiny electrical currents until the patient senses the “aura” that precedes a seizure. Often, seizures can be treated by removing tissue from this part of the brain.

“In the very first patient this was something very unexpected, and we didn’t report it,” said Josef Parvizi at Stanford University in California. But then I was doing functional mapping on the second patient and he suddenly experienced a very similar thing.”

“Its extraordinary that two individuals with very different past experiences respond in a similar way to one or two seconds of very low intensity electricity delivered to the same area of their brain. These patients are normal individuals, they have their IQ, they have their jobs. We are not reporting these findings in sick brains,” Parvizi said.

The men were stimulated with between two and eight milliamps of electrical current, but in tests the doctors administered sham stimulation too. In the sham tests, they told the patients they were about to stimulate the brain, but had switched off the electical supply. In these cases, the men reported no changes to their feelings. The sensation was only induced in a small area of the brain, and vanished when doctors implanted electrodes just five millimetres away.

Parvizi said a crucial follow-up experiment will be to test whether stimulation of the brain region really makes people more determined, or simply creates the sensation of perseverance. If future studies replicate the findings, stimulation of the brain region – perhaps without the need for brain-penetrating electrodes – could be used to help people with severe depression.

The anterior midcingulate cortex seems to be important in helping us select responses and make decisions in light of the feedback we get. Brent Vogt, a neurobiologist at Boston University, said patients with chronic pain and obsessive-compulsive disorder have already been treated by destroying part of the aMCC. “Why not stimulate it? If this would enhance relieving depression, for example, let’s go,” he said.

Thanks to Kebmodee for bringing this to the attention of the It’s Interesting community.