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by Lauren Schenkman Autism is thought to arise during prenatal development, when the brain is spinning its web of excitatory and inhibitory neurons, the main signal-generating cell types in the cerebral cortex. Though this wiring process remains mysterious, one thing seemed certain after two decades of studies in mice: Although both neuron types arise from radial glia, excitatory neurons crop up in the developing cortex, whereas inhibitory neurons, also known as interneurons, originate outside of the cortex and then later migrate into it. Not so in the human brain, according to a study published in December in Nature. A team of researchers led by Tomasz Nowakowski, assistant professor of anatomy at the University of California, San Francisco, used a new viral barcoding method to trace the descendants of radial glial cells from the developing human cortex and found that these progenitor cells can give rise to both excitatory neurons and interneurons. “This is really a paradigm-shifting finding,” Nowakowski says. “It sets up a new framework for studying, understanding and interpreting experimental models of autism mutations.” Nowakowski spoke with Spectrum about the discovery’s implications for studying the origins of autism in the developing brain. Spectrum: Why did you investigate this topic? Tomasz Nowakowski: My lab and I are interested in understanding the early neurodevelopmental events that give rise to the incredible complexity of the human cerebral cortex. We know especially little about the early stages of human development, primarily because a lot of our knowledge comes from mouse models. As we’ve begun to realize over the past decade, the processes that underlie development of the brain in humans and mice can be quite different. © 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: 28165 - Posted: 01.22.2022

by Anna Goshua A variety of traits, including developmental delay and intellectual disability, characterize people with mutations in the autism-linked gene MYT1L, according to a new study. The gene encodes a transcription factor important for cells that make myelin, which insulates nerve cells and is deficient in some forms of autism. The work, published 8 November in Human Genetics, represents the most detailed study of the traits associated with MYT1L mutations to date. “We wanted to gather more cases to bring a clearer clinical and molecular picture of the condition for lab scientists, clinicians and also for patients and families,” says study investigator Juliette Coursimault, a physician-researcher in the genetics department at Rouen University Hospital in France. She and her co-researchers described 62 people, whereas previous literature included only 12 cases. The new characterization will “benefit clinicians’ diagnosis and treatment strategies when a patient with MYT1L mutation arrives in their clinic,” says Brady Maher, a lead investigator at the Lieber Institute for Brain Development at Johns Hopkins University in Baltimore, Maryland, who was not part of the study. The researchers identified and reviewed data for 22 people with MYT1L mutations who had been described in the academic literature, and collected clinical and molecular data from an additional 40 people, aged 1 to 34 years old, with likely or confirmed pathogenic variants of MYT1L. They recruited the participants through Rouen University Hospital and data-sharing networks such as GeneMatcher, which connects clinicians and researchers. © 2021 Simons Foundation

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior; Chapter 3: Neurophysiology: The Generation, Transmission, and Integration of Neural Signals
Related chapters from MM:Chapter 13: Memory and Learning; Chapter 3: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
Link ID: 28122 - Posted: 12.22.2021

by Anna Goshua Researchers have identified hundreds of genes that may contribute to autism, but these genes can’t fully account for the condition’s traits. Studies from the past decade implicate an additional layer of ‘epigenetic’ complexity: chemical tags called methyl groups laid on top of a person’s genetic code. Enzymes that are mutated in some people with autism or related conditions attach the chemical tags to DNA. And that pattern of methyl marks across the genome can influence which genes are active or inactive at any given time. Much remains to be understood about this process, called DNA methylation. Here we describe how and when methylation happens and what researchers know about its relationship to autism. What is methylation? Methylation is the process by which enzymes called methyltransferases deposit methyl chemical groups onto DNA. The presence of these tags usually turns off nearby genes. The complete set of such modifications to the genome over a person’s lifetime is known as the methylome. Most methyl tags are deposited onto the DNA nucleotide called cytosine (C) whenever it occurs next to the nucleotide guanine (G). This CpG methylation begins during gestation and can change across the lifespan. Tags are also sometimes added to cytosines followed by other nucleotides, however. High levels of non-CpG methylation in the brain may be critical for neuron development. 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: 28115 - Posted: 12.15.2021

by Anna Goshua Mice that lack one copy of TBX1, a gene in the autism-linked 22q11.2 chromosomal region, produce too little myelin — the fatty insulation that surrounds neurons — and perform poorly on tasks that measure cognitive speed, according to a new study. The work, published 5 November in Molecular Psychiatry, may offer insight into the mechanisms that underlie impaired cognitive function in some people with a 22q11.2 deletion, and possibly other copy number variants (CNVs). “The myelin changes could potentially emerge as a common neuronal deficit that mediates cognitive changes among many CNV cases,” says lead investigator Noboru Hiroi, professor of pharmacology at the University of Texas Health Science Center at San Antonio. Neuronal axons — the projections that conduct nerve impulses — are coated with myelin, which serves to speed up electrical transmission. The brains of autistic people and several mouse models of autism have disruptions in myelin, previous research has shown. These connecting fibers are the “highways of the brain,” says Valerie Bolivar, research scientist at the New York State Department of Health’s Wadsworth Center in Albany. “If the highway doesn’t work, you can’t get your goods from one place to another as fast.” TBX1 encodes a protein that regulates the expression of other genes during brain development. Deleting one copy of TBX1 leads to social and communication deficits in mice, according to previous studies by Hiroi’s team. © 2021 Simons Foundation

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior; Chapter 3: Neurophysiology: The Generation, Transmission, and Integration of Neural Signals
Related chapters from MM:Chapter 13: Memory and Learning; Chapter 3: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
Link ID: 28103 - Posted: 12.08.2021

by Charles Q. Choi One injection of a potential new gene therapy for Angelman syndrome forestalls many of the neurodevelopmental condition’s key traits, according to early tests in mice. “While additional pharmacology and safety studies are needed, our viral vector can potentially provide transformative therapeutic relief with a single dose,” says lead investigator Benjamin Philpot, professor of neuroscience at the University of North Carolina at Chapel Hill. Angelman syndrome, which affects about one in 20,000 children, is associated with significant developmental delays and, often, autism. It arises from mutations or deletions in the maternal copy of the UBE3A gene, which encodes a protein that helps regulate the levels of other important proteins. There are no treatments specifically for Angelman syndrome, but several gene therapies are under development. One in clinical trials requires repeat injections in the spine and has shown serious side effects at high doses. These therapies all aim to restore UBE3A function in neurons. One challenge, though, is that neurons produce several variants, or ‘isoforms,’ of the UBE3A protein that vary slightly in length; in mice, for example, neurons make two isoforms in a ratio of about four short forms for every long one. In contrast to other gene therapies, the new one generates short and long forms of the UBE3A protein at nearly the same ratio as is seen in mouse neurons. Such proportions “may be important for therapeutic efficacy,” says Eric Levine, professor of neuroscience at the University of Connecticut in Farmington, who was not involved in this study. © 2021 Simons Foundation

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: 28093 - Posted: 12.01.2021

by Niko McCarty Growing numbers of autistic children are diagnosed with the condition before age 3, in the United States, and those diagnoses tend to precede the start of any interventions or developmental services, according to a new study based on parent surveys. Children traversing autism’s ‘diagnostic odyssey’ a decade ago were typically diagnosed years later, and only after they had begun receiving services. The analysis included data from 2,303 autistic children aged 2 to 17 years from the National Survey of Children’s Health, which asks parents questions about the children in their household. The selected participants, split into three groups based on their age, either had a plan for early intervention or had received special services to meet developmental needs. The oldest children, aged 12 to 17 at the time of the survey, had been diagnosed at about age 5 and a half years, on average. Their first intervention or developmental service occurred at around age 5. By contrast, the youngest cohort, aged 2 to 5, had been diagnosed at about age 2 and a half years and started their first intervention or developmental services at roughly the same age. The results are based on parent responses to a question — “How old was your child when a doctor or other health care provider first said they had autism?” — so the findings likely skew toward younger ages than if the researchers had used clinical diagnoses. Also, the study omitted children who did not already have a diagnosis, which might have pushed the average age older. Still, the findings suggest that the time between getting a diagnosis and accessing services is shrinking. © 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: 28084 - Posted: 11.20.2021

by Angie Voyles Askham Two new unpublished studies presented virtually at the 2021 Society for Neuroscience annual meeting offer insights into synapse development: One maps the trajectories of synapse formation across nine species, and the other characterizes the earliest synapses to arise in the human brain. The findings could help researchers better understand how developmental changes may alter synaptic function and contribute to autism. “In order to understand whether something is deviated from neurotypical, you actually have to know what neurotypical is,” says Sam Wang, professor of neuroscience at Princeton University and principal investigator on one of the new studies. Across species, early brain development is defined by a period of exuberant synapse formation, followed by one in which any unnecessary connections are pruned. Disruption to either process may explain some of the atypical development seen in autism, but much about synaptic development remains unknown. For example, when Wang and his colleagues began sifting through the literature to figure out when in development cortical synapses are most abundant and whether that timing shows shared patterns across species, they couldn’t find any studies that had charted the full developmental trajectory from birth to adulthood, says Henk-Jan Boele, a postdoctoral researcher in Wang’s lab who presented the work. So they decided to plot that course themselves, for as many species of mammals as they could find data for. © 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: 28074 - Posted: 11.13.2021

by Angie Voyles Askham The gut microbiome is having a moment. An explosion of research over the past decade has delved into a possible connection between the microbiome and brain conditions, including autism. Once-fringe microbial treatments for autism, such as fecal transplants and probiotic pills, are receiving serious scientific attention and funding. It’s still an open question, however, whether the microbiome has a direct effect on autism traits. The most promising data supporting this idea involve altering a mouse’s gut flora, but it is not clear exactly what the mechanism is or if this work translates to people. And the evidence from human studies linking microbes to autism is thin, if a 2021 review of the literature is any guide. Adding to the uncertainty, new unpublished data from one of the largest human studies yet suggests that the link between an atypical gut microbiome and autism is driven solely by a difference in diet. At least four small firms are spearheading early-stage trials of ‘bug as drug’ treatments for autism-associated traits. But until those trials play out, the role of the microbiome in autism is far from clear, says Gaspar Taroncher-Oldenburg, a consultant on microbiome research for the Simons Foundation, Spectrum’s parent organization. “There’s no denying that the microbiome is part of the [autism] conversation,” Taroncher-Oldenburg says. “But it’s a very complex conversation, and we’re only starting to scratch the surface.” A potential connection between the gut microbiome and autism first surfaced in the 1990s, after parents reported changes in their autistic children’s behavior when the children took antibiotics, which kill some gut bacteria. A 2000 study following up on this idea showed that 8 of 10 autistic children taking an antibiotic had temporary improvements in their speech and sociability. Later work associated an atypical gut microbiome with unusual social behaviors in mice. © 2021 Simons Foundation

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior; Chapter 13: Homeostasis: Active Regulation of the Internal Environment
Related chapters from MM:Chapter 13: Memory and Learning; Chapter 9: Homeostasis: Active Regulation of the Internal Environment
Link ID: 28043 - Posted: 10.20.2021

by Angie Voyles Askham An intranasal form of the hormone oxytocin is no more effective than placebo at increasing social behaviors in autistic children, according to what may be the largest clinical trial of the treatment to date. The results were published today in The New England Journal of Medicine. Because of oxytocin’s role in strengthening social bonds, researchers have considered it as a candidate treatment for autism for more than a decade. Small trials hinted that the hormone could improve social skills in some autistic people, such as those with low blood levels of oxytocin or infants with Prader-Willi syndrome, an autism-related condition. But the new results, based on 250 autistic children, suggest that “oxytocin, at least in its current form, is probably not helpful for the majority of kids with autism,” says Evdokia Anagnostou, professor of pediatrics at University of Toronto in Canada, who was not involved in the new work. The null results “change things,” says lead researcher Linmarie Sikich, associate professor of psychiatry and behavioral sciences at the Duke Center for Autism and Brain Development in Durham, North Carolina. “Most people still felt like there was a good chance that this would be treatment for many people with autism.” This type of research is prone to publication bias, in which non-significant results are less likely to be published than significant ones, says Daniel Quintana, senior researcher in biological psychiatry at the University of Oslo in Norway, who was not involved in the study. For that reason, the new work is “an important contribution to the field,” he says, but “it does not alone put to rest the idea of using intranasal oxytocin as an autism treatment.” © 2021 Simons Foundation

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior; Chapter 5: Hormones and the Brain
Related chapters from MM:Chapter 13: Memory and Learning; Chapter 8: Hormones and Sex
Link ID: 28036 - Posted: 10.16.2021

by Peter Hess Mice with a mutated copy of MYT1L, a leading autism candidate gene, have unusually small brains and many other physical and behavioral traits mirroring those seen in people with similar mutations, according to a study published today in Neuron. The mice represent the first model of MYT1L syndrome, a rare genetic condition marked by autism, intellectual disability, attention deficit hyperactivity disorder (ADHD), obesity and microcephaly, or a smaller-than-average head. “Generating a mouse line is always a gamble,” says lead investigator Joseph Dougherty, associate professor of genetics and psychiatry at Washington University in St. Louis, Missouri. “The stars really aligned for us.” MYT1L encodes a transcription factor, a type of protein that influences gene expression. But few studies have explored how mutations in the gene lead to the traits seen in people, partly because there are likely fewer than 100 cases worldwide. Dougherty and his colleagues used CRISPR to engineer mice with a MYT1L mutation that resembles one identified in an autistic person. The mice have neurons that mature earlier than expected, which could help explain the traits seen in people. As the first mouse model of MYT1L mutations, “this is a landmark piece of work, and is certainly promising for fundamental science exploration and as a preclinical model,” says Charis Eng, chair of the Cleveland Clinic’s Genomic Medicine Institute in Ohio, who was not involved in the work. © 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: 28021 - Posted: 10.06.2021

Katharine Sanderson A large, UK-based study of genetics and autism spectrum disorder (ASD) has been suspended, following criticism that it failed to properly consult the autism community about the goals of the research. Concerns about the study include fears that its data could potentially be misused by other researchers seeking to ‘cure’ or eradicate ASD. The Spectrum 10K study is led by Simon Baron-Cohen, director of the Autism Research Centre (ARC) at the University of Cambridge, UK. The £3-million (US$4-million) project, which is funded by the London-based biomedical funding charity Wellcome, is the largest genetic study of ASD in the United Kingdom. It aims to collect DNA samples, together with information on participants’ mental and physical health, from 10,000 people with autism and their families. This will be used to study the genetic and environmental contributions to ASD, and to co-occurring conditions such as epilepsy and gut-health problems. “If we can understand why these co-occurring conditions are more frequent in autistic people, that could open the door to treatment or management of very distressing symptoms,” says Baron-Cohen. But soon after the study’s high-profile launch on 24 August, people with autism and some ASD researchers expressed concern that it had gone ahead without meaningfully consulting the autism community. Fears about the sharing of genetic data and an alleged failure to properly explain the benefits of the research have been raised by a group called Boycott Spectrum 10K, which is led by people with autism. The group plans to protest outside the ARC premises in Cambridge in October. A separate petition against the study gathered more than 5,000 signatures. © 2021 Springer Nature Limited

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: 28012 - Posted: 09.29.2021

by Giorgia Guglielmi About five years ago, when his younger twin brothers reached their thirties, Giacomo Vivanti started to wonder how the pair, who both have autism, would fare in middle and old age. In particular, he wondered if they might be prone to develop age-related neurological conditions. His brothers didn’t show any signs of ill health or cognitive deterioration, but Vivanti, associate professor of early detection and intervention at the A.J. Drexel Autism Institute in Philadelphia, Pennsylvania, knew that the scientific literature provided few clear answers. “I was pretty shocked to learn that we have such limited knowledge of outcomes as children with autism become adults, and as they age,” Vivanti says. It prompted him to scour four years’ worth of data from Medicaid, the largest healthcare program in the United States, to determine the incidence of neurodegenerative conditions among 30- to 64-year-olds with autism. That group, he and his colleagues reported last month, is about 2.5 times as likely to be diagnosed with early-onset Alzheimer’s or other forms of dementia as the general population. The study is one of a handful that have found higher-than-average rates of neurodegenerative conditions in autistic adults. The risk estimates for Parkinson’s disease in autistic people range from 15 to 20 percent, compared with about 1 percent in the general population. Similarly, the prevalence of dementia is less than 1 percent in non-autistic people but about 4 percent in those with autism. None of these studies offer solid evidence, but their results are strong enough to warrant further investigation, researchers say. © 2021 Simons Foundation

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior; Chapter 16: Psychopathology: Biological Basis of Behavior Disorders
Related chapters from MM:Chapter 13: Memory and Learning; Chapter 12: Psychopathology: The Biology of Behavioral Disorders
Link ID: 28011 - Posted: 09.29.2021

James Cusack Being autistic, for me and the 700,000 other autistic people in the UK, often means spending a lot of time inhabiting a world that doesn’t work well for you. This is why it’s vital that the needs and preferences of autistic people are better understood. A trial of a therapy whose findings were published this week attempts to address this issue by trying to ensure the needs of toddlers who may be autistic are recognised. On one hand, the results are exciting, but they are also complex. Complexity is always hard to communicate. The international research study, led by Prof Andrew Whitehouse at the University of Western Australia in Perth, is technically well designed. It partly replicates a previous trial, and has promising results. Of its two main findings, one is exciting for child development. The second is thornier in how it relates to autism diagnoses. Advertisement The therapy used in the trial was an adapted version of one used among children who are not autistic. It focuses on working with parents to understand how a child prefers to play, and supports them to adapt their own behaviour to match their toddler’s natural way of interacting. Play is one of the fundamental building blocks of how children begin to learn how to interact with people and the world around them. From speaking to autistic people and families, we know that developing communication and language skills alongside finding ways to ensure families feel able to support autistic people are top priorities for autism research. Social communication skills make a huge difference in all our lives. They improve our chances of being able to explain our needs, build stronger relationships and find employment: all things that autistic people can find challenging. © 2021 Guardian News & Media Limited

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: 28010 - Posted: 09.29.2021

by Giorgia Guglielmi Severe infections during early childhood are linked to autism — at least in some boys, a new study in mice and people suggests. The findings were published today in Science Advances. Researchers analyzed the health records of millions of children in the United States and found that boys diagnosed with autism are more likely than non-autistic boys to have had an infection requiring medical attention between age 1 and a half and 4. The study also showed that provoking a strong immune response in newborn mice with only one copy of TSC2, a gene tied to autism, leads to social memory problems in adult male rodents. In people, mutations in TSC2 cause tuberous sclerosis, a condition characterized by non-cancerous tumors and skin growths. About half of all people with tuberous sclerosis also have autism. “If the TSC2 mutation was sufficient to cause autism, then everyone with that mutation would have autism — but they don’t,” says senior investigator Alcino Silva, director of the Integrative Center for Learning and Memory at the University of California, Los Angeles. A child’s chances of having autism rise with severe infections in the child or his mother, previous studies show, but not all children who contract serious infections go on to be diagnosed with autism. The new study is the first to examine the relationship between immune activation and a specific genetic variant tied to autism, Silva says. The findings suggest that genetics and severe infection represent a ‘two-hit’ scenario for autism. © 2021 Simons Foundation

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior; Chapter 15: Emotions, Aggression, and Stress
Related chapters from MM:Chapter 13: Memory and Learning; Chapter 11: Emotions, Aggression, and Stress
Link ID: 27996 - Posted: 09.18.2021

by Niko McCarty Brain scans from 16 mouse models of autism reveal at least four distinct patterns of brain activity, a new study suggests. The findings lend fresh support to the popular idea that autism is associated with a range of brain ‘signatures.’ Telltale neural signatures of autism have long proved elusive, with functional magnetic resonance imaging (fMRI) and other brain scanning technologies shouldering the blame for scattered and inconsistent results. “One big question is whether there’s a single signature of dysfunction in the brain of people with autism. And many people consider that to be, like, something that there must be,” says study investigator Alessandro Gozzi, senior researcher at the Istituto Italiano di Tecnologia in Rovereto, Italy. “If we’ve not found it yet, the blame must be on the method: fMRI.” The method gauges small changes in blood flow and oxygenation as an indirect measure of brain activity. For the new study, published in Molecular Psychiatry in August, Gozzi and his colleagues used fMRI to study brain connectivity patterns — or which brain regions ‘talk’ to each other, and to what degree. Brain regions are considered to be in communication if they have synchronous oscillations in blood flow. To tackle the question of reproducibility in fMRI, the researchers conducted their analysis in mice, anesthetizing the animals and fixing their heads in place to prevent any motion that could perturb brain signals. “We moved to a model organism where we can control, in exquisite detail, many of the factors that are considered to be at the basis of this variability, this unreliability in imaging,” Gozzi says. © 2021 Simons Foundation

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior; Chapter 2: Functional Neuroanatomy: The Cells and Structure of the Nervous System
Related chapters from MM:Chapter 13: Memory and Learning; Chapter 2: Neurophysiology: The Generation, Transmission, and Integration of Neural Signals
Link ID: 27982 - Posted: 09.11.2021

by Angie Voyles Askham Male mice exposed to atypically low levels of a placental hormone in the womb have altered brain development and asocial behaviors, according to a new study. The findings may help explain why preterm birth — which coincides with a deficiency in hormones made by the placenta — is linked to an increased likelihood of having autism. The hormone, called allopregnanolone, crosses the blood-brain barrier, binds to receptors for the chemical messenger gamma-aminobutyric acid (GABA) and helps regulate aspects of neurodevelopment, including the growth of new neurons. Its levels typically peak in the fetus during the second half of gestation. In the new study, researchers engineered a mouse model to have low fetal levels of allopregnanolone, mimicking the hormone’s loss due to preterm birth or placental dysfunction. The male mice in particular have structural changes in the cerebellum, a brain region known for balance and motor control, and exhibit more pronounced autism-like traits than control mice or female model mice. The new model “has a good translational potential for understanding the underlying mechanisms of sex differences in neurodevelopmental conditions such as autism,” says Amanda Kentner, professor of psychology at the Massachusetts College of Pharmacy and Health Sciences in Boston, who was not involved in the work. Injecting a pregnant mouse with allopregnanolone partway through gestation decreased the likelihood that its offspring would have autism-like traits, the researchers found. © 2021 Simons Foundation

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior; Chapter 5: Hormones and the Brain
Related chapters from MM:Chapter 13: Memory and Learning; Chapter 8: Hormones and Sex
Link ID: 27977 - Posted: 09.04.2021

by Peter Hess Some mutations in SCN2A, a gene reliably linked to autism, change social behaviors in mice by dampening the electrical activity of their neurons, according to a new study. SCN2A encodes a sodium channel that helps neurons send electrical signals. So-called ‘gain-of-function’ mutations make the channel hyperactive and can lead to epilepsy, whereas ‘loss-of-function’ mutations diminish its activity and are typically associated with autism. The mice in the new study carry the latter type and, as a result, have fewer functioning sodium channels than usual. The animals also react to unfamiliar mice in an atypical way, mirroring social behaviors seen in autistic people with similar SCN2A mutations. “We’re in the position of really connecting a single mutation, or at least a defect in the channel, to the behavior,” says lead investigator Geoffrey Pitt, professor of medicine at Weill Cornell Medicine in New York. “The message that our paper shows is that loss-of-function mutations and decreased sodium current can lead to behaviors.” This study confirms previous work showing that autism-linked mutations in SCN2A dampen channel activity in neurons, and further connects the loss-of-function mutations to clear changes in behavior, says Kevin Bender, associate professor of neurology at the University of California San Francisco, who was not involved in the work. “The behavioral results were actually some of the most robust that I’ve seen in this field to date.” © 2021 Simons Foundation

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior; Chapter 3: Neurophysiology: The Generation, Transmission, and Integration of Neural Signals
Related chapters from MM:Chapter 13: Memory and Learning; Chapter 3: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
Link ID: 27968 - Posted: 08.28.2021

By Pamela Feliciano As social beings, when thinking about autism we tend to focus on its social challenges, such as difficulty communicating, making friends and showing empathy. I am a geneticist and the mother of a teenage boy with autism. I too worry most about whether he’ll have the conversational skills to do basic things like grocery shopping or whether he will ever have a real friend. But I assure you that the nonsocial features of autism are also front and center in our lives: intense insistence on sameness, atypical responses to sensory stimuli and a remarkable ability to detect small details. Many attempts have been made to explain all the symptoms of autism holistically, but no one theory has yet explained all the condition’s puzzling and diverse features. Now, a growing number of neurocognitive scientists think that many traits found in people with autism spectrum disorder (ASD) may be explained centrally by impairments in predictive skills—and have begun testing this hypothesis. Generally, the human brain determines what’s coming next based on the status quo, plus what we recall from previous experiences. Scientists theorize that people with ASD have differences that disturb their ability to predict. It’s not that people with autism can’t make predictions; it’s that their predictions are flawed because they perceive the world “too accurately.” Their predictions are less influenced by prior experiences and more influenced by what they are experiencing in the moment. They overemphasize the “now.” © 2021 Scientific American

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: 27936 - Posted: 08.07.2021

by Peter Hess Neurons in mice with an autism-linked mutation sprout extraneous protrusions, an overgrowth that tracks with above-average motor learning. The animals lose both attributes when treated with an experimental drug that suppresses the activity of the Ras-ERK/MAPK cell signaling pathway, according to a new study. This pathway helps reshape neurons to change the strength of their connections in response to learning or other influences, part of a process known as neuroplasticity. “There is a balance between learning and forgetting in the brain,” says lead researcher Stelios Smirnakis, associate professor of neurology at Harvard University. “Understanding these pathways and how to balance them is of critical importance to a number of neurological disorders.” Hyperactivation of the Ras-ERK/MAPK pathway, which is also involved in cell growth, has been linked to cancer as well as multiple autism-related conditions. “A lot of genes in that pathway have been shown to underlie several forms of autism,” says Maria Chahrour, assistant professor of neuroscience at the University of Texas Southwestern Medical Center in Dallas, who was not involved in the study. “The pathway itself is also dysregulated in several forms of autism, so there’s a potential convergence.” The mice in the new work had an extra copy of the gene MECP2. As in previous studies and some other autism mouse models, the MECP2-duplication mice showed enhanced motor learning, mastering how to balance on a rotating rod more quickly than their wildtype counterparts. The animals’ motor learning prowess offers a model for studying how the repetitive behaviors seen in people with autism develop, the researchers say. © 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: 27918 - Posted: 07.21.2021

by Giorgia Guglielmi Autism research has long focused on genes involved in the formation of neurons and the function of synapses. Mutations in these genes were the first to be solidly linked to the condition and its traits. Over the past decade, however, several studies have implicated a second class of genes: those involved in the remodeling of chromatin — the complex of DNA and proteins that makes up chromosomes. These ‘chromatin regulators,’ which can influence whether other genes are turned on or off, are sometimes mutated in people with autism or other neurodevelopmental conditions. Scientists are just beginning to understand how these mutations can alter brain development. Why is chromatin remodeling important? If the chromosomes of a single human cell were stretched out and joined together end to end, their DNA would measure about 6.5 feet long. To fit inside a nucleus no wider than one-tenth of a human hair, the DNA strand wraps around histone proteins to form a series of bead-like structures called nucleosomes. Together these beads make up the chromatin. When a stretch of DNA is tightly packed into a nucleosome, it is inaccessible to the proteins that turn genes on and off by way of a process called transcription. For cells to express the right genes at the right time, their DNA needs to transition from tightly to loosely packed coils, a process carried out by a group of proteins called chromatin remodeling complexes. © 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: 27891 - Posted: 07.06.2021