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Brain-Signal Proteins Evolved Before Animals Did

Viviane Callier Our human brains can seem like a crowning achievement of evolution, but the roots of that achievement run deep: The modern brain arose from hundreds of millions of years of incremental advances in complexity. Evolutionary biologists have traced that progress back through the branch of the animal family tree that includes all creatures with central nervous systems, the bilaterians, but it is clear that fundamental elements of the nervous system existed much earlier. How much earlier has now been made dramatically clear by a recent discovery by a team of researchers at the University of Exeter in the United Kingdom. They found that the chemical precursors of two important neurotransmitters, or signaling molecules used in nervous systems, appear in all the major animal groups that preceded creatures with central nervous systems. The big surprise, however, is that these molecules are also present in single-celled relatives of animals, called choanoflagellates. This finding shows that animal neuropeptides originated before the evolution of even the very first animals. The discovery “solves a long-standing question about when and how animal neuropeptides evolved,” said Pawel Burkhardt, who studies the evolutionary origin of neurons at the Sars International Center for Marine Molecular Biology in Norway. It also indicates that at least some of the signaling molecules fundamental to the operation of our brains first evolved for an entirely different purpose in organisms that consisted of only a single cell. Animal nervous systems are made of neurons that connect to each other, zipping information across synapses with a variety of small peptide neurotransmitters. These peptides are the language with which neurons speak to each other. All Rights Reserved © 2022

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior; Chapter 4: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
Related chapters from MM:Chapter 13: Memory and Learning; Chapter 4: Development of the Brain
Link ID: 28354 - Posted: 06.04.2022

Spinal Fluid From Young Mice Sharpened Memories of Older Rodents

By Benjamin Mueller Five years ago, Tal Iram, a young neuroscientist at Stanford University, approached her supervisor with a daring proposal: She wanted to extract fluid from the brain cavities of young mice and to infuse it into the brains of older mice, testing whether the transfers could rejuvenate the aging rodents. Her supervisor, Tony Wyss-Coray, famously had shown that giving old animals blood from younger ones could counteract and even reverse some of the effects of aging. But the idea of testing that principle with cerebrospinal fluid, the hard-to-reach liquid that bathes the brain and spinal cord, struck him as such a daunting technical feat that trying it bordered on foolhardy. “When we discussed this initially, I said, ‘This is so difficult that I’m not sure this is going to work,’” Dr. Wyss-Coray said. Dr. Iram persevered, working for a year just to figure out how to collect the colorless liquid from mice. On Wednesday, she reported the tantalizing results in the journal Nature: A week of infusions of young cerebrospinal fluid improved the memories of older mice. The finding was the latest indication that making brains resistant to the unrelenting changes of older age might depend less on interfering with specific disease processes and more on trying to restore the brain’s environment to something closer to its youthful state. “It highlights this notion that cerebrospinal fluid could be used as a medium to manipulate the brain,” Dr. Iram said. Turning that insight into a treatment for humans, though, is a more formidable challenge, the authors of the study said. The earlier studies about how young blood can reverse some signs of aging have led to recent clinical trials in which blood donations from younger people were filtered and given to patients with Alzheimer’s or Parkinson’s disease. But exactly how successful those treatments might be, much less how widely they can be used, remains unclear, scientists said. And the difficulties of working with cerebrospinal fluid are steeper than those involved with blood. Infusing the fluid of a young human into an older patient is probably not possible; extracting the liquid generally requires a spinal tap, and scientists say that there are ethical questions about how to collect enough cerebrospinal fluid for infusions. © 2022 The New York Times Company

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior; Chapter 17: Learning and Memory
Related chapters from MM:Chapter 13: Memory and Learning; Chapter 13: Memory and Learning
Link ID: 28327 - Posted: 05.14.2022

She Was Missing a Chunk of Her Brain. It Didn’t Matter

Grace Browne In early February 2016, after reading an article featuring a couple of scientists at the Massachusetts Institute of Technology who were studying how the brain reacts to music, a woman felt inclined to email them. “I have an interesting brain,” she told them. EG, who has requested to go by her initials to protect her privacy, is missing her left temporal lobe, a part of the brain thought to be involved in language processing. EG, however, wasn’t quite the right fit for what the scientists were studying, so they referred her to Evelina Fedorenko, a cognitive neuroscientist, also at MIT, who studies language. It was the beginning of a fruitful relationship. The first paper based on EG’s brain was recently published in the journal Neuropsychologia, and Fedorenko’s team expects to publish several more. For EG, who is in her fifties and grew up in Connecticut, missing a large chunk of her brain has had surprisingly little effect on her life. She has a graduate degree, has enjoyed an impressive career, and speaks Russian—a second language–so well that she has dreamed in it. She first learned her brain was atypical in the autumn of 1987, at George Washington University Hospital, when she had it scanned for an unrelated reason. The cause was likely a stroke that happened when she was a baby; today, there is only cerebro-spinal fluid in that brain area. For the first decade after she found out, EG didn't tell anyone other than her parents and her two closest friends. “It creeped me out,” she says. Since then, she has told more people, but it's still a very small circle that is aware of her unique brain anatomy. © Condé Nast Britain 2022.

Related chapters from BN: Chapter 19: Language and Lateralization; Chapter 7: Life-Span Development of the Brain and Behavior
Related chapters from MM:Chapter 15: Language and Lateralization; Chapter 13: Memory and Learning
Link ID: 28295 - Posted: 04.20.2022

Poverty and the Developing Brain

Joan L. Luby, M.D., John N. Constantino, M.D., Deanna M. Barch, Ph.D. Numerous studies of children in the US across decades have shown striking correlations between poverty and less-than-optimal physical and mental health and developmental outcomes. Trauma, poor health care, inadequate nutrition, and increased exposures to psychosocial stress and environmental toxins—all of which have significant negative developmental impact—are likely to be involved. The effects of elevated stress on child-caregiver relationships appear to be particularly detrimental, unsurprising in that nurturing and supportive caregiver relationships are foundational for healthy development in early childhood. For adults whose job options are unconducive to their role as parents (such as working multiple jobs or night shift hours), or for whom family support is unavailable, or for those do not have the material resources they need, the resulting stress may result in sleep disruption, depression, and anxiety—all of which translate to poor developmental trajectories for their children. Other health and developmental risks often associated with poverty include lead and other pollutants in air and water, poor nutrition (often related to living in “food desert” areas where healthy foods such as fresh fruits and vegetables are scarce), neighborhood violence, and trauma. “Toxic stress” that exceeds a child’s ability to adapt can occur when the burden of stressful life experience overwhelms the brain’s regulatory capacity, or when the compensatory abilities of brain and body are compromised. A lack of cognitive stimulation (due to such factors as the absence of books and educational materials in the home, poor immersion in language, and a lack of after school or other enrichment activities) or disruption of sleep and circadian rhythms (by neighborhood noise or parents’ irregular work schedules) is likely to impact brain development and emotional and behavioral regulation when these systems are rapidly developing. © 2022 The Dana Foundation.

Your brain expands and shrinks over time — these charts show how

Max Kozlov When neuroscientist Jakob Seidlitz took his 15-month-old son to the paediatrician for a check-up last week, he left feeling unsatisfied. There wasn’t anything wrong with his son — the youngster seemed to be developing at a typical pace, according to the height and weight charts the physician used. What Seidlitz felt was missing was an equivalent metric to gauge how his son’s brain was growing. “It is shocking how little biological information doctors have about this critical organ,” says Seidlitz, who is based at the University of Pennsylvania in Philadelphia. Soon, he might be able to change that. Working with colleagues, Seidlitz has amassed more than 120,000 brain scans — the largest collection of its kind — to create the first comprehensive growth charts for brain development. The charts show visually how human brains expand quickly early in life and then shrink slowly with age. The sheer magnitude of the study, published in Nature on 6 April1, has stunned neuroscientists, who have long had to contend with reproducibility issues in their research, in part because of small sample sizes. Magnetic resonance imaging (MRI) is expensive, meaning that scientists are often limited in the number of participants they can enrol in experiments. “The massive data set they assembled is extremely impressive and really sets a new standard for the field,” says Angela Laird, a cognitive neuroscientist at Florida International University in Miami. Even so, the authors caution that their database isn’t completely inclusive — they struggled to gather brain scans from all regions of the globe. The resulting charts, they say, are therefore just a first draft, and further tweaks would be needed to deploy them in clinical settings. If the charts are eventually rolled out to paediatricians, great care will be needed to ensure that they are not misinterpreted, says Hannah Tully, a paediatric neurologist at the University of Washington in Seattle. “A big brain is not necessarily a well-functioning brain,” she says. © 2022 Springer Nature Limited

Cells Blaze Their Own Trails to Navigate Through the Body

Elena Renken Even when it’s not apparent, cells in our tissues and organs are constantly on the move. In fact, the ability of cells to get where they need to go is essential to our health and survival. Skin cells migrate to heal wounds. Immune system cells migrate to fight infections. “Every day, you look at your body and it’s not changing much,” said Peter Devreotes, a professor of cell biology at the Johns Hopkins University School of Medicine. “But the cells within it are migrating constantly.” It starts from the earliest stages of life. When we are embryos just a few weeks old, a special population of “neural crest” cells in our back suddenly spreads through the body to become a wide range of essential tissues — bones, cartilage and nerves in the face, tendons, pigment cells in the skin, parts of the heart and more. But how do these cells know where to go? Studies long suggested that they were following chemical trails to their routes. Biologists traditionally saw these chemical gradients as simple and the cells as mere followers: Like dogs trotting toward the scent of food, the cells sensed the gradient and followed the stream of signals back to the source. Countless examples of this have been found among bacteria and other cells navigating through the wild, as well as inside larger organisms. When you nick your skin, for instance, the tissue around the cut releases a cloud of molecules that attract immune cells nearby. The immune cells crawl toward it and stave off infection. Yet scientists also came to understand that this system can’t sustain many of the migrations that unfold in the body. The structure of simple passive gradients is too fragile and too easily disrupted. Simple gradients like these don’t always reach far enough to guide cells’ lengthier journeys, and they may dissipate too quickly to maintain migrations that take longer. Raising the sensitivity of the cells might seem like a way to offset those problems, but then cells might often be too flooded with signals to sense where they come from. For a simple gradient to work, it has to be perfect, and nothing can go awry. But in reality, cells must find a way to navigate under all kinds of conditions. All Rights Reserved © 2022

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior
Related chapters from MM:Chapter 13: Memory and Learning
Link ID: 28261 - Posted: 03.30.2022

Gut molecule linked to decreased myelination in mouse brains

by Angie Voyles Askham Mice chemically coaxed to produce high levels of an autism-linked gut molecule have anxiety-like behavior and unusual patterns of brain connectivity, according to a study published today in Nature. The findings present a direct mechanism by which the gut could send signals to the brain and alter development, the researchers say. “It’s a true mechanistic paper, [like] the field has been asking for,” says Jane Foster, professor of psychiatry and behavioral neurosciences at McMaster University in Hamilton, Canada, who was not involved in the study. Although it’s not clear that this exact signaling pathway is happening in people, she says, “this is the sort of work that’s going to get us that answer.” The molecule, 4-ethylphenol (4EP), is produced by gut microbes in mice and people. An enzyme in the colon and liver converts 4EP to 4-ethylphenyl sulfate (4EPS), which then circulates in the blood. Mice exposed to a maternal immune response in the womb have atypically high blood levels of 4EPS, as do some autistic people, previous research shows. And injecting mice with the molecule increases behaviors indicative of anxiety. But it wasn’t clear how the molecule could contribute to those traits. In the new work, researchers show that 4EPS can enter the brain and that its presence is associated with altered brain connectivity and a decrease in myelin — the insulation around axons that helps conduct electrical signals. Boosting the function of myelin-producing cells, the team found, eases the animals’ anxiety. “This is one of the first — maybe, arguably, the first — demonstrations of a specific microbe molecule that has such a profound impact on a complex behavior,” says lead researcher Sarkis Mazmanian, professor of microbiology at the California Institute of Technology in Pasadena. “How it’s doing it, we still need to understand.” without the engineered enzymes, they showed increased anxiety-like behaviors, © 2022 Simons Foundation

Related chapters from BN: Chapter 13: Homeostasis: Active Regulation of the Internal Environment; Chapter 7: Life-Span Development of the Brain and Behavior
Related chapters from MM:Chapter 9: Homeostasis: Active Regulation of the Internal Environment; Chapter 13: Memory and Learning
Link ID: 28205 - Posted: 02.16.2022

Hollis Cline: Leapfrogging over gaps in autism research

by Laura Dattaro Early in her first postdoctoral position, Hollis Cline first showed her hallmark flair for creative problem-solving. Cline, who goes by Holly, and her adviser, neuroscientist Martha Constantine-Paton, wanted to study the brain’s ‘topographical maps’ — internal representations of sensory input from the external world. These maps are thought to shape a person’s ability to process sensory information — filtering that can go awry in autism and other neurodevelopmental conditions. No one knew just how these maps formed or what could potentially disrupt them. Cline and Constantine-Paton, who was then at Yale University and is now emerita professor of brain and cognitive sciences at the Massachusetts Institute of Technology, weren’t sure how to find out. But as a first step, the pair decided to take the plunge with an unusual animal model: the frog — specifically, a spotted greenish-brown species called Rana pipiens, or the northern leopard frog. The amphibians spend two to three months as tadpoles, a span during which their brains change rapidly and visibly — unlike in mammals, which undergo similar stages of development inside of the mother’s body. These traits made it possible for Cline and Constantine-Paton to introduce changes and repeatedly watch their effects in real time. “That’s an extended period when you can actually have access to the developing brain,” Cline says. The unorthodox approach paid off. Cline, 66, now professor of neuroscience at the Scripps Research Institute in La Jolla, California, worked out that a receptor for the neurotransmitter glutamate, which had been shown to be important for learning and memory, also mediated how visual experiences influence the developing topographical map. She later created a novel live imaging technique to visualize frog neurons’ development over time and, sticking with frogs over the ensuing decades, went on to make fundamental discoveries about how sensory experiences shape brain development and sensory processing. © 2022 Simons Foundation

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior
Related chapters from MM:Chapter 13: Memory and Learning
Link ID: 28179 - Posted: 02.02.2022

A newborn lost large parts of his brain. Today, he’s an athletic college grad.

By Meeri Kim Kellie Carr and her 13-year-old son, Daniel, sat in the waiting room of a pediatric neurology clinic for yet another doctor’s appointment in 2012. For years, she struggled to find out what was causing his weakened right side. It wasn’t an obvious deficit, by any means, and anyone not paying close attention would see a normal, healthy teenage boy. At that point, no one had any idea that Daniel had suffered a massive stroke as a newborn and lost large parts of his brain as a result. “It was the largest stroke I’d ever seen in a child who hadn’t died or suffered extreme physical and mental disability,” said Nico Dosenbach, the pediatric neurologist at Washington University School of Medicine in St. Louis who finally diagnosed him using a magnetic resonance imaging (MRI) scan. "If I saw the MRI first, I would have assumed this kid's probably in a wheelchair, has a feeding tube and might be on a ventilator," Dosenbach said. "Because normally, when a child is missing that much brain, it's bad." But Daniel — as an active, athletic young man who did fine in school — defied all logic. Before the discovery of the stroke, his mother had noticed some odd mannerisms, such as zipping up his coat or eating a burger using only his left hand. When engaged, his right hand often served as club-like support instead of a dexterous appendage with fingers. Daniel excelled as a left-handed pitcher in competitive baseball, but his coach found it unusual that he would always switch the glove to his left hand when catching the ball. Medical professionals tried to help — first his pediatrician, followed by an orthopedic doctor who sent him to physical therapy — but no one could figure out the root cause. They tried constraint-induced movement therapy, which forces patients to use the weaker arm by immobilizing the other in a cast, but Daniel soon rebelled and broke himself free. © 1996-2022 The Washington Post

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior; Chapter 19: Language and Lateralization
Related chapters from MM:Chapter 13: Memory and Learning; Chapter 15: Language and Lateralization
Link ID: 28174 - Posted: 01.26.2022

Cash Aid to Poor Mothers Increases Brain Activity in Babies

By Jason DeParle WASHINGTON — A study that provided poor mothers with cash stipends for the first year of their children’s lives appears to have changed the babies’ brain activity in ways associated with stronger cognitive development, a finding with potential implications for safety net policy. The differences were modest — researchers likened them in statistical magnitude to moving to the 75th position in a line of 100 from the 81st — and it remains to be seen if changes in brain patterns will translate to higher skills, as other research offers reason to expect. Still, evidence that a single year of subsidies could alter something as profound as brain functioning highlights the role that money may play in child development and comes as President Biden is pushing for a much larger program of subsidies for families with children. “This is a big scientific finding,” said Martha J. Farah, a neuroscientist at the University of Pennsylvania, who conducted a review of the study for the Proceedings of the National Academy of Sciences, where it was published on Monday. “It’s proof that just giving the families more money, even a modest amount of more money, leads to better brain development.” Another researcher, Charles A. Nelson III of Harvard, reacted more cautiously, noting the full effect of the payments — $333 a month — would not be clear until the children took cognitive tests. While the brain patterns documented in the study are often associated with higher cognitive skills, he said, that is not always the case. © 2022 The New York Times Company

COVID generation: how is the pandemic affecting kids’ brains?

Melinda Wenner Moyer Like many paediatricians, Dani Dumitriu braced herself for the impact of the SARS-CoV-2 coronavirus when it first surged in her wards. She was relieved when most newborn babies at her hospital who had been exposed to COVID-19 seemed to do just fine. Knowledge of the effects of Zika and other viruses that can cause birth defects meant that doctors were looking out for problems. But hints of a more subtle and insidious trend followed close behind. Dumitriu and her team at the NewYork–Presbyterian Morgan Stanley Children’s Hospital in New York City had more than two years of data on infant development — since late 2017, they had been analysing the communication and motor skills of babies up to six months old. Dumitriu thought it would be interesting to compare the results from babies born before and during the pandemic. She asked her colleague Morgan Firestein, a postdoctoral researcher at Columbia University in New York City, to assess whether there were neurodevelopmental differences between the two groups. A few days later, Firestein called Dumitriu in a panic. “She was like, ‘We’re in a crisis, I don’t know what to do, because we not only have an effect of a pandemic, but it’s a significant one,’” Dumitriu recalled. She was up most of that night, poring over the data. The infants born during the pandemic scored lower, on average, on tests of gross motor, fine motor and communication skills compared with those born before it (both groups were assessed by their parents using an established questionnaire)1. It didn’t matter whether their birth parent had been infected with the virus or not; there seemed to be something about the environment of the pandemic itself. Dumitriu was stunned. “We were like, oh, my God,” she recalled. “We’re talking about hundreds of millions of babies.” Although children have generally fared well when infected with SARS-CoV-2, preliminary research suggests that pandemic-related stress during pregnancy could be negatively affecting fetal brain development in some children. Moreover, frazzled parents and carers might be interacting differently or less with their young children in ways that could affect a child’s physical and mental abilities.

Brain wrinkles and folds matter – researchers are studying the mechanics of how they form

Mir Jalil Razavi Weiying Dai The human brain has been called the most complex object in the known universe. And with good reason: It has around 86 billion neurons and several hundred thousand miles of axon fibers connecting them. Unsurprisingly, the process of brain folding that results in the brain’s characteristic bumps and grooves is also highly complex. Despite decades of speculation and research, the underlying mechanism behind this process remains poorly understood. As biomechanics and computer science researchers, we have spent several years studying the mechanics of brain folding and ways to visualize and map the brain, respectively. Figuring out this complexity may help researchers better diagnose and treat developmental brain disorders such as lissencephaly, or smooth brain, and epilepsy. Because many neurological disorders emerge at the early stages of development, understanding how brain folding works can provide useful insights into normal and pathological brain function. The mechanics of brain folding The brain is made of two layers. The outer layer, called the cerebral cortex, is composed of folded gray matter made up of small blood vessels and the spherical cell bodies of billions of neurons. The inner layer is composed of white matter, consisting mostly of the neurons’ elongated tails, called myelinated axons. When a story fascinates you, remember: Your donations make it possible Illustration of cross section of brain showing axonal pathways transitioning from gray matter into white matter. In recent years, researchers have shown that mechanics, or the forces that objects exert on one another, play an important role in the growth and folding of the brain. © 2010–2021, The Conversation US, Inc.

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior
Related chapters from MM:Chapter 13: Memory and Learning
Link ID: 28119 - Posted: 12.18.2021

Finding a path forward for fragile X drugs

by Chloe Williams In June 2020, cannabidiol hit what has become a familiar hurdle in fragile X research: Like many previous drug candidates, it missed its primary target in clinical testing. Among 109 young people with fragile X syndrome who took the drug and 101 who took a placebo, researchers saw no meaningful difference in a rating of social avoidance. A secondary analysis factored into the trial’s original design offered a glimmer of hope, though. A subset of 91 participants showed marked improvement on the same measure after treatment with the drug, according to unpublished findings. Among that group, the gene underlying fragile X syndrome, called FMR1, is awash with methyl groups, which block its expression of the protein FMRP. By contrast, the remaining participants have only partially methylated copies of the gene and may make more FMRP. “Looking at methylation was pretty important to find that subgroup that had the most optimal response,” says Randi Hagerman, medical director of the MIND Institute at the University of California, Davis, who led one of the trial sites. The subgroup’s improvements meet only the minimum threshold for one measure of statistical significance — they have a p-value of 0.02 — and the results await replication, something the company running the trials, Zynerba Pharmaceuticals, is working on. But the trial’s design reflects a fundamental shift in how researchers are trying to advance drug development for fragile X syndrome, one of the leading inherited causes of intellectual disability and autism. © 2021 Simons Foundation

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior
Related chapters from MM:Chapter 13: Memory and Learning
Link ID: 28003 - Posted: 09.25.2021

X chromosome exerts extra influence on brain development

by Rachel Zamzow The X chromosome holds stronger-than-expected genetic sway over the structure of several brain regions, a new study finds. The X-linked genes that may underlie this oversized influence have ties to autism and intellectual disability. “There were already hints that the X chromosome was likely to be conspicuous, with how involved it is with the brain,” says lead investigator Armin Raznahan, chief of the section on developmental neurogenomics at the U.S. National Institute of Mental Health. Many X chromosome genes — including those at the root of several autism-related conditions, such as fragile X syndrome and Rett syndrome — are expressed in the brain, for example. But the new findings suggest that the X chromosome, despite containing only 5 percent of the human genome, has a privileged role in shaping the brain — one that may be particularly relevant to developmental conditions. What’s more, this influence may be stronger in men than in women, the study shows. “What they’re showing is X is fundamentally different,” says David Glahn, professor of psychology at Harvard University, who was not involved in the new study. “It’s off the scale.” Research over the past decade has linked genetic variation to shifts in brain features, such as overall size or patterns of connectivity between regions, Glahn says. But “the X chromosome and the Y chromosome are fundamentally understudied,” because including them requires extra analytical legwork, he says. © 2021 Simons Foundation

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior; Chapter 12: Sex: Evolutionary, Hormonal, and Neural Bases
Related chapters from MM:Chapter 13: Memory and Learning; Chapter 8: Hormones and Sex
Link ID: 27992 - Posted: 09.15.2021

How personalized brain organoids could help us demystify disorders

By Laura Sanders Clumps of brain cells grown from the stem cells of two people with a neurological syndrome show signs of the disorder. The results, published August 23 in Nature Neuroscience, suggest that personalized brain organoids could be powerful tools to understand complex disorders. Researchers are eager to create brain organoids, human stem cells coaxed into becoming 3-D blobs of brain cells, because of their ability to mimic human brains in the lab (SN: 2/20/18). In the current study, researchers grew two kinds of brain organoids. One kind, grown from healthy people’s stem cells, produced complex electrical activity that echoed the brain waves a full-sized brain makes. These waves, created by the coordinated firing of many nerve cells, are part of how the brain keeps information moving (SN: 3/13/18). The researchers also grew organoids using cells from a 25-year-old woman and a 5-year-old girl with Rett syndrome, a developmental disorder marked by seizures, autism and developmental lags. Rett syndrome is thought to be caused by changes in a gene called MECP2, mutations that the lab-grown organoids carried as well. These organoids looked like those grown from healthy people, but behaved differently in some ways. Their nerve cells fired off signals that were too synchronized and less varied. Some of the brain waves these organoids produced are reminiscent of a brain having a seizure, in which a bolus of electrical activity scrambles normal brain business. © Society for Science & the Public 2000–2021.

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior
Related chapters from MM:Chapter 13: Memory and Learning
Link ID: 27976 - Posted: 09.04.2021

Scientists Discover “Gorditas” and Other Novel Brain Cell Types

Amanda Heidt Scientists have discovered two types of glial cells in the brains of adult mice—an astrocyte and an oligodendrocyte progenitor cell—after nudging neural stem cells to rise from dormancy, according to a study published June 10 in Science. The results suggest new roles for glial cells, best known for providing support to neurons, and could prompt a better understanding of how brains remain plastic into adulthood, when the vast majority of neurons no longer undergo cell division. This study is “a very important addition to the whole story about these fascinating [stem] cells that exist in the adult brain of rodents that have the capacity to generate new cells,” says Arturo Alvarez-Buylla, a developmental neuroscientist at the University of California, San Francisco, who was not involved in the work. “Understanding adult stem cells is fundamental to really know the kinds of plasticity that exist after the developmental period is over.” Most mammalian brain cells, be they neurons or glia, are generated during embryonic development, and reservoirs of stem cells become largely, if not entirely, dormant in adulthood. The small trickle of activity that is left can help the brain respond to change, sometimes by generating new neurons to help with learning or by producing cells in response to injury or disease. One pool exists in the brains of adult humans and mice, in an area called the ventricular-subventricular zone (V-SVZ). The walls of the two lateral ventricles, cavities filled with cerebrospinal fluid, are lined with stem cells, and along these walls, the cells have a regional identity—where a stem cell lies on the wall dictates what it differentiates into. This feature has been well-characterized for neuronal subtypes, which are synthesized within discrete domains on the lateral wall. Glial cells are known to be generated at low levels along the septal wall, but the specific subtypes remain unknown because the cells along this wall generally remain inactive. © 1986–2021 The Scientist.

Ageism: The Brain Strikes Back!

Tanya T. Nguyen, M.D., Dilip V. Jeste, M.D. In James Hilton’s 1933 novel Lost Horizons, Shangri-La was a magical utopia where people lived well beyond 100 years. But now, less than a century later, it seems we are well on our way to making Hilton’s vision a reality. The US Census Bureau reported in 2020 that the average life expectancy has increased from 47 in 1900 to over 80 years today, while the number of people over age 60 exceeds children under 15 for the first time ever. By 2060, the average lifespan will approach 90 years. Astonishingly, more than half of the babies born today will live to age 100 and beyond, which will make Hilton’s seemingly far-fetched vision come to pass. One might think that people living longer would represent an enormous, thrilling milestone. But unfortunately, aging is rarely perceived that way. The increase in older people—metaphorically termed a “silver tsunami” since the 1980s—has economic implications, including unimaginable healthcare costs. Certain segments of western culture sadly equate aging with such “d” words as degeneration, decline, disability, diseases, dementia, depression, and death. Policy makers and economists are outspoken in their fear that spending money on older people’s care will mean less money for children and younger adults, who represent the future. This attitude—commonly labeled ageism—is analogous to such phenomena as sexism, racism, and bias against certain sexual orientations. Ageism has made many older people feel guilty about living longer and becoming a potential burden. They think—and are encouraged by society to think—that aging is an incurable disease. © 2021 The Dana Foundation.

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior
Related chapters from MM:Chapter 13: Memory and Learning
Link ID: 27911 - Posted: 07.17.2021

Keeping a Close Eye on Organoids

Philip M. Boffey I was astonished to learn while writing a column on the brain-computer interface in 2019 that patients with amyotrophic lateral sclerosis (ALS), whose brain signals were fed into a computer, could control a complex robotic arm, having it pick up a pitcher and pour water into a glass, just by thinking about it. So you can imagine my surprise when I learned that scientists have achieved comparably difficult tasks—not with signals from a human brain—but simply from a clump of stem calls in a Petri dish. The achievement is clearly described in Alan Alda’s Clear+Vivid podcast featuring Alysson Muotri, a Brazilian citizen who is director of the stem cell program at University of California, San Diego, where much of this pioneering work was performed. The podcast is a useful complement to a more comprehensive report issued on April 8 by the National Academies of Sciences, Engineering, and Medicine. As Alda’s introduction explains, Muotri uses factors that drive skin cells to revert to stem cells and then become brain tissues that self-organize, forming “brain organoids in a dish. Muotri, who has a personal interest because he has a son with autism, hopes to learn how early brain development can change course in conditions like autism and epilepsy—and how our brains differ from those of our evolutionary? cousins, the Neanderthals. Although some people call what he has created “brains” or “mini-brains” in a dish, Muotri is more circumspect, describing them as “brain organoids.” © 2021 The Dana Foundation.

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior
Related chapters from MM:Chapter 13: Memory and Learning
Link ID: 27886 - Posted: 07.03.2021

White matter and human behavior

Christopher M. Filley One of the most enduring themes in human neuroscience is the association of higher brain functions with gray matter. In particular, the cerebral cortex—the gray matter of the brain's surface—has been the primary focus of decades of work aiming to understand the neurobiological basis of cognition and emotion. Yet, the cerebral cortex is only a few millimeters thick, so the relative neglect of the rest of the brain below the cortex has prompted the term “corticocentric myopia” (1). Other regions relevant to behavior include the deep gray matter of the basal ganglia and thalamus, the brainstem and cerebellum, and the white matter that interconnects all of these structures. On page 1304 of this issue, Zhao et al. (2) present compelling evidence for the importance of white matter by demonstrating genetic influences on structural connectivity that invoke a host of provocative clinical implications. Insight into the importance of white matter in human behavior begins with its anatomy (3–5) (see the figure). White matter occupies about half of the adult human brain, and some 135,000 km of myelinated axons course through a wide array of tracts to link gray matter regions into distributed neural networks that serve cognitive and emotional functions (3). The human brain is particularly well interconnected because white matter has expanded more in evolution than gray matter, which has endowed the brain of Homo sapiens with extensive structural connectivity (6). The myelin sheath, white matter's characteristic feature, appeared late in vertebrate evolution and greatly increased axonal conduction velocity. This development enhanced the efficiency of distributed neural networks, expanding the transfer of information throughout the brain (5). Information transfer serves to complement the information processing of gray matter, where neuronal cell bodies, synapses, and a variety of neurotransmitters are located (5). The result is a brain with prodigious numbers of both neurons and myelinated axons, which have evolved to subserve the domains of attention, memory, emotion, language, perception, visuospatial processing, executive function (5), and social cognition (7). © 2021 American Association for the Advancement of Science.

Related chapters from BN: Chapter 18: Attention and Higher Cognition; Chapter 7: Life-Span Development of the Brain and Behavior
Related chapters from MM:Chapter 14: Attention and Higher Cognition; Chapter 13: Memory and Learning
Link ID: 27862 - Posted: 06.19.2021

‘The working of the brain resembles drug dealers in Albuquerque’

Andrew Anthony David Eagleman, 50, is an American neuroscientist, bestselling author and presenter of the BBC series The Brain, as well as co-founder and chief executive officer of Neosensory, which develops devices for sensory substitution. His area of speciality is brain plasticity, and that is the subject of his new book, Livewired, which examines how experience refashions the brain, and shows that it is a much more adaptable organ than previously thought. For the past half-century or more the brain has been spoken of in terms of a computer. What are the biggest flaws with that particular model? It’s a very seductive comparison. But in fact, what we’re looking at is three pounds of material in our skulls that is essentially a very alien kind of material to us. It doesn’t write down memories, the way we think of a computer doing it. And it is capable of figuring out its own culture and identity and making leaps into the unknown. I’m here in Silicon Valley. Everything we talk about is hardware and software. But what’s happening in the brain is what I call livewire, where you have 86bn neurons, each with 10,000 connections, and they are constantly reconfiguring every second of your life. Even by the time you get to the end of this paragraph, you’ll be a slightly different person than you were at the beginning. In what way does the working of the brain resemble drug dealers in Albuquerque? It’s that the brain can accomplish remarkable things without any top-down control. If a child has half their brain removed in surgery, the functions of the brain will rewire themselves on to the remaining real estate. And so I use this example of drug dealers to point out that if suddenly in Albuquerque, where I happened to grow up, there was a terrific earthquake, and half the territory was lost, the drug dealers would rearrange themselves to control the remaining territory. It’s because each one has competition with his neighbours and they fight over whatever territory exists, as opposed to a top-down council meeting where the territory is distributed. And that’s really the way to understand the brain. It’s made up of billions of neurons, each of which is competing for its own territory. © 2021 Guardian News & Media Limited

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