Chapter 2. Neurophysiology: The Generation, Transmission, and Integration of Neural Signals

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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

Keyword: Development of the Brain; Brain imaging
Link ID: 28277 - Posted: 04.09.2022

Linda Geddes A completely locked-in patient is able to type out words and short sentences to his family, including what he would like to eat, after being implanted with a device that enables him to control a keyboard with his mind. The findings, published in Nature Communications, overturn previous assumptions about the communicative abilities of people who have lost all voluntary muscle control, including movement of the eyes or mouth, as well as giving a unique insight into what it’s like to be in a “locked in” state. Locked-in syndrome – also known as pseudocoma - is a rare condition, where people are conscious and can see, hear, and smell, but are unable to move or speak due to complete paralysis of their voluntary muscles, eg as a result of the progressive neurodegenerative disease amyotrophic lateral sclerosis (ALS). Advertisement Some can communicate by blinking or moving their eyes, but those with completely locked-in syndrome (CLIS) cannot even control their eye muscles. In 2017, doctors at the University of Tübingen in Germany enabled three patients with CLIS to answer “yes” or “no” to questions by detecting telltale patterns in their brain activity, using a technology called functional near-infrared spectroscopy (fNIRS). The advance generated widespread media coverage, and prompted the parents of the current patient, who was diagnosed with ALS in 2015, to write to the medical team, saying he was losing the ability to communicate with his eye movements, and could they help. The problem with using fNIRS to help CLIS patients to communicate is that it is relatively slow, and only gives the correct answer 70% of the time, meaning questions have to be repeated to get a reliable answer. “It was always our goal to enable a patient in a completely locked down state to spell out words, but with a classification accuracy of 70%, it is almost impossible to enable free spelling,” said Dr Ujwal Chaudhary, a biomedical engineer and managing director of ALS Voice gGmbH in Mössingen, Germany, who co-led the research. © 2022 Guardian News & Media Limited

Keyword: ALS-Lou Gehrig's Disease ; Movement Disorders
Link ID: 28250 - Posted: 03.23.2022

By Matt Richtel For two decades, researchers have used brain-imaging technology to try to identify how the structure and function of a person’s brain connects to a range of mental-health ailments, from anxiety and depression to suicidal tendencies. But a new paper, published Wednesday in Nature, calls into question whether much of this research is actually yielding valid findings. Many such studies, the paper’s authors found, tend to include fewer than two dozen participants, far shy of the number needed to generate reliable results. “You need thousands of individuals,” said Scott Marek, a psychiatric researcher at the Washington University School of Medicine in St. Louis and an author of the paper. He described the finding as a “gut punch” for the typical studies that use imaging to try to better understand mental health. Studies that use magnetic-resonance imaging technology commonly temper their conclusions with a cautionary statement noting the small sample size. But enlisting participants can be time-consuming and expensive, ranging from $600 to $2,000 an hour, said Dr. Nico Dosenbach, a neurologist at Washington University School of Medicine and another author on the paper. The median number of subjects in mental-health-related studies that use brain imaging is around 23, he added. But the Nature paper demonstrates that the data drawn from just two dozen subjects is generally insufficient to be reliable and can in fact yield “massively inflated” findings,” Dr. Dosenbach said. For their analysis, the researchers examined three of the largest studies using brain-imaging technology to reach conclusions about brain structure and mental health. All three studies are ongoing: the Human Connectome Project, which has 1,200 participants; the Adolescent Brain Cognitive Development, or A.B.C.D., study, with 12,000 participants; and the U.K. Biobank study, with 35,700 participants. The authors of the Nature paper looked at subsets of data within those three studies to determine whether smaller slices were misleading or “reproducible,” meaning that the findings could be considered scientifically valid. © 2022 The New York Times Company

Keyword: Brain imaging
Link ID: 28245 - Posted: 03.19.2022

by Niko McCarty The ‘opto’ in optogenetics — the powerful method some autism researchers use to control neurons in mice and other animals — comes from the Greek optós, meaning visible. It’s a nod to the blue light used to switch on select neurons. A new technique can do the same, albeit with something invisible: sound. In a study published in Nature Communications this month, researchers engineered neurons in the motor cortex of mice to express an ultrasound-sensitive ion channel protein called hsTRPA1. They placed an ultrasound transducer near the animal’s skull and switched it on. The response? A flex of a muscle, a perceptible twitch. The approach, called sonogenetics, enables noninvasive control over any neural circuit that can be manipulated with optogenetics, an invasive method, says lead investigator Sreekanth Chalasani, associate professor in the Molecular Neurobiology Laboratory at the Salk Institute for Biological Studies in La Jolla, California. Spectrum spoke to Chalasani about his early experiments in Caenorhabditis elegans, lucky number 63 and how sonogenetics could one day have clinical applications. Spectrum: Our readers might be familiar with optogenetics, but I’m assuming sonogenetics is new for most people. Sreekanth Chalasani: Yeah. Well, the idea in sonogenetics is that we want to manipulate things noninvasively. Ultrasound can travel through bone and skin, into the body. We’ve been using it for decades. It’s safe. The question is: Can we leverage it to get in the body and control cells, like with optogenetics? S: Literally controlling cells with sound. SC: Right. In optogenetics, light triggers action potentials in cells that have a channelrhodopsin, or opsin, protein. In sonogenetics, we wanted a protein that would let us have that same level of cellular control. But finding that protein has been difficult. Lots of groups have been looking for these proteins, and we were fortunate to find one. © 2022 Simons Foundation

Keyword: Brain imaging
Link ID: 28227 - Posted: 03.02.2022

Natalia Mesa More than a decade ago, scientists developed optogenetics, a method to turn cells on and off with light. The technique allows scientists to spur or suppress cells' electrical activity with just the flip of a switch to tease apart the roles of specific cell types. But because light doesn’t penetrate deep into tissues, scientists need to surgically implant light sources to illuminate cells below the surface of the skin or skull. In a new study published today (February 9) in Nature Communications, researchers report they’ve found a way to use ultrasound to noninvasively activate mouse neurons, both in culture and in the brains of living animals. The technique, which the authors call sonogenetics, elicits electrical activity in a subset of brain cells that have been genetically engineered to respond to sound waves. “We know that ultrasound is safe,” study coauthor Sreekanth Chalasani, a neuroscientist in Salk’s Molecular Neurobiology Laboratory, tells The Scientist. “The potential for neuronal control is huge. It has applications for pacemakers, insulin pumps, and other therapies that we’re not even thinking about. Jamie Tyler, a biomedical engineer at the University of Alabama at Birmingham who was not involved in the study but has previously collaborated with some of its authors, tells The Scientist that the work represents “more than just a step forward” in being able to use ultrasound to control neural activity: “It shows that sonogenetics is a viable technique in mammalian cells.” © 1986–2022 The Scientist.

Keyword: Brain imaging
Link ID: 28199 - Posted: 02.12.2022

In 2016, Science magazine ranked Randy L. Buckner among the top 10 most influential brain scientists of the modern era. He explains the road to discovering the default network, the pattern of brain activity triggered as we think about the past and the future. Q: Why don’t we begin with a brief description of what the default network is, how and when it was discovered, and why it’s important. Randy L. Buckner: In the 1990s, neuroscientists were just starting to do functional imaging studies. For the first time, we had brain scanners that could see the mind at work. We were like kids in a candy store in the sense that we no longer needed a scalpel to see the brain; the new technology allowed us to safely discern information out about what parts of the brain people used when given different tasks and different kinds of visual or auditory stimuli. I was a graduate student at the time at Washington University and one of my mentors, Marcus Raichle, was at the forefront of positron emission tomography (PET), an imaging technique that measures physiological changes in the brain and shows where blood flow is increasing due to brain activity. This is when many of us first became aware of the Dana Foundation, which was helping fund our work. I was a Dana fellow in those early days, and this was an exciting time in neuroscience. In early studies, we often asked participants to perform very simple tasks: read and say words, detect colors in pictures, or try to recognize whether a viewed word was on an earlier studied list. The imaging revealed the parts of the brain involved in their responses. But what jumped out at us was something unexpected: When people weren’t asked for a response or given a specific task, much of their brain still remained active. © 2022 The Dana Foundation.

Keyword: Brain imaging
Link ID: 28171 - Posted: 01.26.2022

Chloe Tenn Whether they’re predicting the outcomes of sports games or opening jars, the intelligence of octopuses and their cephalopod kin has fascinated avid sports fans and scientists alike (not that the two groups are mutually exclusive). However, insights into the animals’ brains have been limited, as structural data has come from low-tech methods such as dissection. Wen-Sung Chung, a University of Queensland Brain Institute neurobiologist who focuses on marine species, explains that octopuses have “probably the biggest centralized brain in invertebrates,” with multiple layers and lobes. Some species have more than 500 million neurons, he adds—compared to around 70 million in lab mice—making cephalopods especially intriguing as models for neuroscience. Chung and his colleagues decided to bring cephalopod neuroscience into the 21st century: using cutting-edge MRI, they probed the brains of four cephalopod species. They were especially interested in exploring whether cephalopod brain structures reflect the environments they live in. Indeed, the team reports numerous structural differences between species that live on reefs and those that dwell in deeper waters in a November 18 Current Biology paper. Giovanna Ponte, an evolutionary marine biologist at Stazione Zoologica Anton Dohrn Napoli in Italy who was not involved with the work, tells The Scientist that while this isn’t the first study to look for neurological correlates underlying ecological differences in cephalopods, it offers a new technological approach to investigating these animals’ brain morphology and diversity, and most importantly, “is the first time that there is . . . a comparative approach between different species.” © 1986–2022 The Scientist.

Keyword: Evolution; Brain imaging
Link ID: 28166 - Posted: 01.22.2022

Monique Brouillette Last summer a group of Harvard University neuroscientists and Google engineers released the first wiring diagram of a piece of the human brain. The tissue, about the size of a pinhead, had been preserved, stained with heavy metals, cut into 5,000 slices and imaged under an electron microscope. This cubic millimeter of tissue accounts for only one-millionth of the entire human brain. Yet the vast trove of data depicting it comprises 1.4 petabytes’ worth of brightly colored microscopy images of nerve cells, blood vessels and more. “It is like discovering a new continent,” said Jeff Lichtman of Harvard, the senior author of the paper that presented these results. He described a menagerie of puzzling features that his team had already spotted in the human tissue, including new types of cells never seen in other animals, such as neurons with axons that curl up and spiral atop each other and neurons with two axons instead of one. These findings just scratched the surface: To search the sample completely, he said, would be a task akin to driving every road in North America. Lichtman has spent his career creating and contemplating these kinds of neural wiring diagrams, or connectomes — comprehensive maps of all the neural connections within a part or the entirety of a living brain. Because a connectome underpins all the neural activity associated with a volume of brain matter, it is a key to understanding how its host thinks, feels, moves, remembers, perceives, and much more. Don’t expect a complete wiring diagram for a human brain anytime soon, however, because it’s technically infeasible: Lichtman points out that the zettabyte of data involved would be equivalent to a significant chunk of the entire world’s stored content today. In fact, the only species for which there is yet a comprehensive connectome is Caenorhabditis elegans, the humble roundworm. Nevertheless, the masses of connectome data that scientists have amassed from worms, flies, mice and humans are already having a potent effect on neuroscience. And because techniques for mapping brains are getting faster, Lichtman and other researchers are excited that large-scale connectomics — mapping and comparing the brains of many individuals of a species — is finally becoming a reality. Share this article Simons Foundation All Rights Reserved © 2021

Keyword: Brain imaging
Link ID: 28104 - Posted: 12.08.2021

Yongsoo Kim The brain plays an essential role in how people navigate the world by generating both thought and behavior. Despite being one of the most vital organs of life, it takes up only 2% of human body volume. How can something so small perform such complex tasks? Luckily, modern tools like brain mapping have allowed neuroscientists like me to answer this exact question. By mapping out how all the cell types in the brain are organized and examining how they communicate with one another, neuroscientists can better understand how brains normally work, and what happens when certain cell parts go missing or malfunction. The task of understanding the inner workings of the brain has fascinated both philosophers and scientists for centuries. Aristotle proposed that the brain is where spirit resides. Leonardo da Vinci drew anatomical depictions of the brain with wax embedding. And Santiago Ramón y Cajal, with his 1906 Nobel Prize-winning work on the cellular structure of the nervous system, made one of the first breakthroughs that led to modern neuroscience as we know it. Using a new way to visualize individual cells called Golgi staining, a method pioneered by Nobel co-winner Camillo Golgi, and microscopic examination of brain tissue, Cajal established the seminal neuron doctrine. This principle states that neurons, among the main types of brain cells, communicate with one another via the gaps between them called synapses. These findings launched a race to understand the cellular composition of the brain and how brain cells are connected to one another. Conversation US, Inc.

Keyword: Brain imaging
Link ID: 28085 - Posted: 11.20.2021

By David Dobbs Chronic pain is both one of the world’s most costly medical problems, affecting one in every five people, and one of the most mysterious. In the past two decades, however, discoveries about the crucial role played by glia — a set of nervous system cells once thought to be mere supports for neurons — have rewritten chronic pain science. These findings have given patients and doctors a hard-science explanation that chronic pain previously lacked. By doing so, this emerging science of chronic pain is beginning to influence care — not by creating new treatments, but by legitimizing chronic pain so that doctors take it more seriously. Although glia are scattered throughout the nervous system and take up almost half its space, they long received far less scientific attention than neurons, which do the majority of signaling in the brain and body. Some types of glia resemble neurons, with roughly starfish-like bodies, while others look like structures built with Erector sets, their long, straight structural parts joined at nodes. When first discovered in the mid-1800s, glia — from the Greek word for glue — were thought to be just connective tissue holding neurons together. Later they were rebranded as the nervous system’s janitorial staff, as they were found to feed neurons, clean up their waste and take out their dead. In the 1990s they were likened to secretarial staff when it was discovered they also help neurons communicate. Research over the past 20 years, however, has shown that glia don’t just support and respond to neuronal activity like pain signals — they often direct it, with enormous consequences for chronic pain. If you’re hearing this for the first time and you’re one of the billion-plus people on Earth who suffer from chronic pain (meaning pain lasting beyond three to six months that has no apparent cause or has become independent of the injury or illness that caused it), you might be tempted to say that your glia are botching their pain-management job. © 2021 The New York Times Company

Keyword: Pain & Touch; Glia
Link ID: 28075 - Posted: 11.13.2021

Kate Wild “The skull acts as a bastion of privacy; the brain is the last private part of ourselves,” Australian neurosurgeon Tom Oxley says from New York. Oxley is the CEO of Synchron, a neurotechnology company born in Melbourne that has successfully trialled hi-tech brain implants that allow people to send emails and texts purely by thought. In July this year, it became the first company in the world, ahead of competitors like Elon Musk’s Neuralink, to gain approval from the US Food and Drug Administration (FDA) to conduct clinical trials of brain computer interfaces (BCIs) in humans in the US. Synchron has already successfully fed electrodes into paralysed patients’ brains via their blood vessels. The electrodes record brain activity and feed the data wirelessly to a computer, where it is interpreted and used as a set of commands, allowing the patients to send emails and texts. BCIs, which allow a person to control a device via a connection between their brain and a computer, are seen as a gamechanger for people with certain disabilities. “No one can see inside your brain,” Oxley says. “It’s only our mouths and bodies moving that tells people what’s inside our brain … For people who can’t do that, it’s a horrific situation. What we’re doing is trying to help them get what’s inside their skull out. We are totally focused on solving medical problems.” BCIs are one of a range of developing technologies centred on the brain. Brain stimulation is another, which delivers targeted electrical pulses to the brain and is used to treat cognitive disorders. Others, like imaging techniques fMRI and EEG, can monitor the brain in real time. “The potential of neuroscience to improve our lives is almost unlimited,” says David Grant, a senior research fellow at the University of Melbourne. “However, the level of intrusion that would be needed to realise those benefits … is profound”. © 2021 Guardian News & Media Limited

Keyword: Brain imaging; Language
Link ID: 28070 - Posted: 11.09.2021

By Emily Anthes The brain of a fruit fly is the size of a poppy seed and about as easy to overlook. “Most people, I think, don’t even think of the fly as having a brain,” said Vivek Jayaraman, a neuroscientist at the Janelia Research Campus of the Howard Hughes Medical Institute in Virginia. “But, of course, flies lead quite rich lives.” Flies are capable of sophisticated behaviors, including navigating diverse landscapes, tussling with rivals and serenading potential mates. And their speck-size brains are tremendously complex, containing some 100,000 neurons and tens of millions of connections, or synapses, between them. Since 2014, a team of scientists at Janelia, in collaboration with researchers at Google, have been mapping these neurons and synapses in an effort to create a comprehensive wiring diagram, also known as a connectome, of the fruit fly brain. The work, which is continuing, is time-consuming and expensive, even with the help of state-of-the-art machine-learning algorithms. But the data they have released so far is stunning in its detail, composing an atlas of tens of thousands of gnarled neurons in many crucial areas of the fly brain. And now, in an enormous new paper, being published on Tuesday in the journal eLife, neuroscientists are beginning to show what they can do with it. By analyzing the connectome of just a small part of the fly brain — the central complex, which plays an important role in navigation — Dr. Jayaraman and his colleagues identified dozens of new neuron types and pinpointed neural circuits that appear to help flies make their way through the world. The work could ultimately help provide insight into how all kinds of animal brains, including our own, process a flood of sensory information and translate it into appropriate action. © 2021 The New York Times Company

Keyword: Brain imaging; Evolution
Link ID: 28057 - Posted: 10.30.2021

By Emily Anthes The brain of a fruit fly is the size of a poppy seed and about as easy to overlook. “Most people, I think, don’t even think of the fly as having a brain,” said Vivek Jayaraman, a neuroscientist at the Janelia Research Campus of the Howard Hughes Medical Institute in Virginia. “But, of course, flies lead quite rich lives.” Flies are capable of sophisticated behaviors, including navigating diverse landscapes, tussling with rivals and serenading potential mates. And their speck-size brains are tremendously complex, containing some 100,000 neurons and tens of millions of connections, or synapses, between them. Since 2014, a team of scientists at Janelia, in collaboration with researchers at Google, have been mapping these neurons and synapses in an effort to create a comprehensive wiring diagram, also known as a connectome, of the fruit fly brain. The work, which is continuing, is time-consuming and expensive, even with the help of state-of-the-art machine-learning algorithms. But the data they have released so far is stunning in its detail, composing an atlas of tens of thousands of gnarled neurons in many crucial areas of the fly brain. And now, in an enormous new paper, being published on Tuesday in the journal eLife, neuroscientists are beginning to show what they can do with it. By analyzing the connectome of just a small part of the fly brain — the central complex, which plays an important role in navigation — Dr. Jayaraman and his colleagues identified dozens of new neuron types and pinpointed neural circuits that appear to help flies make their way through the world. The work could ultimately help provide insight into how all kinds of animal brains, including our own, process a flood of sensory information and translate it into appropriate action. It is also a proof of principle for the young field of modern connectomics, which was built on the promise that constructing detailed diagrams of the brain’s wiring would pay scientific dividends. “It’s really extraordinary,” Dr. Clay Reid, a senior investigator at the Allen Institute for Brain Science in Seattle, said of the new paper. “I think anyone who looks at it will say connectomics is a tool that we need in neuroscience — full stop.” © 2021 The New York Times Company

Keyword: Brain imaging; Evolution
Link ID: 28055 - Posted: 10.27.2021

Barbara Jacquelyn Sahakian Christelle Langley Katrin Amunts While humans have walked on the Moon and sent probes all over the solar system, our understanding of our own brain is still severely lacking. We do not have complete knowledge of how brain structure, chemicals and connectivity interact to produce our thoughts and behaviours. But this isn’t from an absence of ambition. It is nearly eight years since the start of the Human Brain Project (HBP) in Europe, which aims to unravel the brain’s mysteries. After a difficult start, the project has made substantial discoveries and innovation, relevant for tackling clinical disorders, as well as technological advances – and it has two more years to go. It has also created EBRAINS, an open research infrastructure built on the scientific advances and tools developed by the project’s research teams, and making them available to the scientific community via a shared digital platform – a new achievement for collaborative research and instrumental in the achievements listed below. 1. Human brain atlas The project has created a unique multilevel human brain atlas based on several aspects of brain organisation, including its structure on the smallest of scales, its function and connectivity. This atlas provides a large number of tools to visualise data and work with them. Researchers can automatically extract data from the atlas using a special tool to run a simulation for modelling the brains of specific patients. This can help to inform clinicians of the optimal treatment option. © 2010–2021, The Conversation US, Inc.

Keyword: Brain imaging
Link ID: 28031 - Posted: 10.13.2021

Alison Abbott Imagine looking at Earth from space and being able to listen in on what individuals are saying to each other. That’s about how challenging it is to understand how the brain works. From the organ’s wrinkled surface, zoom in a million-fold and you’ll see a kaleidoscope of cells of different shapes and sizes, which branch off and reach out to each other. Zoom in a further 100,000 times and you’ll see the cells’ inner workings — the tiny structures in each one, the points of contact between them and the long-distance connections between brain areas. Scientists have made maps such as these for the worm1 and fly2 brains, and for tiny parts of the mouse3 and human4 brains. But those charts are just the start. To truly understand how the brain works, neuroscientists also need to know how each of the roughly 1,000 types of cell thought to exist in the brain speak to each other in their different electrical dialects. With that kind of complete, finely contoured map, they could really begin to explain the networks that drive how we think and behave. Such maps are emerging, including in a series of papers published this week that catalogue the cell types in the brain. Results are streaming in from government efforts to understand and stem the increasing burden of brain disorders in their ageing populations. These projects, launched over the past decade, aim to systematically chart the brain’s connections and catalogue its cell types and their physiological properties. It’s an onerous undertaking. “But knowing all the brain cell types, how they connect with each other and how they interact, will open up an entirely new set of therapies that we can’t even imagine today,” says Josh Gordon, director of the US National Institute of Mental Health (NIMH) in Bethesda, Maryland. © 2021 Springer Nature Limited

Keyword: Brain imaging; Development of the Brain
Link ID: 28029 - Posted: 10.09.2021

Amanda Heidt Qin Liu studies sneezing for a personal reason: her entire family suffers from seasonal allergies. “Until you experience something chronically, it is really hard to appreciate how disruptive it can be,” says Liu, a neuroscientist at Washington University in St. Louis. And given the role of sneezing in pathogen transmission, a better understanding of the molecular underpinnings of the phenomenon could one day help scientists mitigate or treat infectious diseases. When Liu first started looking into the mechanisms governing sneezing, she found that scientists know surprisingly little about how this process works. While prior research had identified a region in the brains of cats and humans that is active during sneezing, the exact pathways involved in turning a stimulus like pollen or spicy food into a sneeze remained unknown. To study sneezing in more detail, Liu and her team developed a new model by exposing mice to irritants such as histamine and capsaicin—a chemical in spicy peppers—and characterizing the physical properties of their resulting sneezes. Then, focusing on that previously discovered sneeze center, located in the brain’s ventromedial spinal trigeminal nucleus (SpV), Liu attempted to map the neural pathway. SNEEZE TRIGGER: When exposed to allergens such as histamine or chemical irritants such as capsaicin (1), sensory neurons in the noses of mice produce a peptide called neuromedin B (NMB). This signaling molecule binds to neurons in a region of the brainstem known as the ventromedial spinal trigeminal nucleus (SpV), which is known to be active during sneezing (2). These neurons send electrical signals (3) to neurons in another brainstem region called the caudal ventral respiratory group (cVRG), which controls exhalation, thus driving the initiation and propagation of sneezing (4). Ablating the nasal neurons or disrupting NMB signaling led to a significantly reduced sneezing reflex in the mice. WEB | PDF © 1986–2021 The Scientist.

Keyword: Brain imaging; Pain & Touch
Link ID: 28014 - Posted: 10.02.2021

Abby Olena Delivering anything therapeutic to the brain has long been a challenge, largely due to the blood-brain barrier, a layer of cells that separates the vessels that supply the brain with blood from the brain itself. Now, in a study published August 12 in Nature Biotechnology, researchers have found that double-stranded RNA-DNA duplexes with attached cholesterol can enter the brains of both mice and rats and change the levels of targeted proteins. The results suggest a possible route to developing drugs that could target the genes implicated in disorders such as muscular dystrophy and amyotrophic lateral sclerosis (ALS). “It’s really exciting to have a study that’s focused on delivery to the central nervous system” with antisense oligonucleotides given systemically, says Michelle Hastings, who investigates genetic disease at the Rosalind Franklin University of Medicine and Science in Chicago and was not involved in the study. The authors “showed that it works for multiple targets, some clinically relevant.” In 2015, Takanori Yokota of Tokyo Medical and Dental University and colleagues published a study showing that a so-called heteroduplex oligonucleotide (HDO)—consisting of a short chain of both DNA and an oligonucleotide with modified bases paired with complementary RNA bound to a lipid on one end—was successful at decreasing target mRNA expression in the liver. Yokota’s team later joined forces with researchers at Ionis Pharmaceuticals to determine whether HDOs could cross the blood-brain barrier and target mRNA in the central nervous system. © 1986–2021 The Scientist.

Keyword: Genes & Behavior; ALS-Lou Gehrig's Disease
Link ID: 27998 - 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

Keyword: Autism; Brain imaging
Link ID: 27982 - Posted: 09.11.2021

Jordana Cepelewicz Neuroscientists are the cartographers of the brain’s diverse domains and territories — the features and activities that define them, the roads and highways that connect them, and the boundaries that delineate them. Toward the front of the brain, just behind the forehead, is the prefrontal cortex, celebrated as the seat of judgment. Behind it lies the motor cortex, responsible for planning and coordinating movement. To the sides: the temporal lobes, crucial for memory and the processing of emotion. Above them, the somatosensory cortex; behind them, the visual cortex. Not only do researchers often depict the brain and its functions much as mapmakers might draw nations on continents, but they do so “the way old-fashioned mapmakers” did, according to Lisa Feldman Barrett, a psychologist at Northeastern University. “They parse the brain in terms of what they’re interested in psychologically or mentally or behaviorally,” and then they assign the functions to different networks of neurons “as if they’re Lego blocks, as if there are firm boundaries there.” But a brain map with neat borders is not just oversimplified — it’s misleading. “Scientists for over 100 years have searched fruitlessly for brain boundaries between thinking, feeling, deciding, remembering, moving and other everyday experiences,” Barrett said. A host of recent neurological studies further confirm that these mental categories “are poor guides for understanding how brains are structured or how they work.” Neuroscientists generally agree about how the physical tissue of the brain is organized: into particular regions, networks, cell types. But when it comes to relating those to the task the brain might be performing — perception, memory, attention, emotion or action — “things get a lot more dodgy,” said David Poeppel, a neuroscientist at New York University. All Rights Reserved © 2021

Keyword: Brain imaging; Attention
Link ID: 27963 - Posted: 08.25.2021

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.

Keyword: Development of the Brain; Neurogenesis
Link ID: 27921 - Posted: 07.24.2021