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An Advance in Brain Research That Was Once Considered Impossible

By Carl Zimmer The human brain is so complex that scientific brains have a hard time making sense of it. A piece of neural tissue the size of a grain of sand might be packed with hundreds of thousands of cells linked together by miles of wiring. In 1979, Francis Crick, the Nobel-prize-winning scientist, concluded that the anatomy and activity in just a cubic millimeter of brain matter would forever exceed our understanding. “It is no use asking for the impossible,” Dr. Crick wrote. Forty-six years later, a team of more than 100 scientists has achieved that impossible, by recording the cellular activity and mapping the structure in a cubic millimeter of a mouse’s brain — less than one percent of its full volume. In accomplishing this feat, they amassed 1.6 petabytes of data — the equivalent of 22 years of nonstop high-definition video. “This is a milestone,” said Davi Bock, a neuroscientist at the University of Vermont who was not involved in the study, which was published Wednesday in the journal Nature. Dr. Bock said that the advances that made it possible to chart a cubic millimeter of brain boded well for a new goal: mapping the wiring of the entire brain of a mouse. “It’s totally doable, and I think it’s worth doing,” he said. More than 130 years have passed since the Spanish neuroscientist Santiago Ramón y Cajal first spied individual neurons under a microscope, making out their peculiar branched shapes. Later generations of scientists worked out many of the details of how a neuron sends a spike of voltage down a long arm, called an axon. Each axon makes contact with tiny branches, or dendrites, of neighboring neurons. Some neurons excite their neighbors into firing voltage spikes of their own. Some quiet other neurons. Human thought somehow emerges from this mix of excitation and inhibition. But how that happens has remained a tremendous mystery, largely because scientists have been able to study only a few neurons at a time. In recent decades, technological advances have allowed scientists to start mapping brains in their entirety. In 1986, British researchers published the circuitry of a tiny worm, made up of 302 neurons. In subsequent years, researchers charted bigger brains, such as the 140,000 neurons in the brain of a fly. © 2025 The New York Times Company

To make a meaningful contribution to neuroscience, fMRI must break out of its silo

Avram Holmes. Human thought and behavior emerge through complex and reciprocal interactions that link microscale molecular and cellular processes with macroscale functional patterns. Functional MRI (fMRI), one of the most common methods for studying the human brain, detects these latter patterns through the “blood oxygen level dependent,” or BOLD, signal, a composite measure of both neural and vascular signals that reflects an indirect measure of brain activity. Despite an enormous investment by scientific funders and the research community in the use of fMRI, though, researchers still don’t fully understand the underlying mechanisms that drive individual or population-level differences measured via in-vivo brain imaging, which limits our ability to interpret those data. For fMRI to meaningfully contribute to progress in neuroscience, we need to develop research programs that link phenomena across levels, from genes and molecules to cells, circuits, networks and behavior. Without a concerted effort in this direction, fMRI will remain a methodological spandrel, a byproduct of technological development rather than a tool explicitly designed to reveal neural mechanisms, generating isolated datapoints that are left unintegrated with broader scientific theory or progress. Recently, the human functional neuroimaging community has turned a critical eye toward its own methods and findings. These debates have led to field-wide initiatives calling for larger and more diverse study samples, better phenotypic reliability and findings that generalize across populations. But researchers have put relatively little emphasis on contextualizing the resulting work across levels of analysis or on deciphering the biological mechanism that may underpin changes to the BOLD signal across groups and individual people or over the lifespan. Appeals to better integrate the different levels of neuroscience are not new. But despite persuasive arguments, fMRI researchers have largely remained scientifically siloed, isolated by a nearly ubiquitous focus on a single level of analysis and a rigid adherence to a select set of imaging methods. Our work is typically presented inside of field-specific echo chambers—departmental or group seminars, topic-specific journals and society meetings—where our methodological and analytic choices go unchallenged. What progress can we expect to make if we remain isolated from other fields of study? © 2025 Simons Foundation

Related chapters from BN: Chapter 2: Functional Neuroanatomy: The Cells and Structure of the Nervous System
Related chapters from MM:Chapter 2: Neurophysiology: The Generation, Transmission, and Integration of Neural Signals
Link ID: 29735 - Posted: 04.09.2025

The Mysterious Flow of Fluid in the Brain

By Veronique Greenwood Encased in the skull, perched atop the spine, the brain has a carefully managed existence. It receives only certain nutrients, filtered through the blood-brain barrier; an elaborate system of protective membranes surrounds it. That privileged space contains a mystery. For more than a century, scientists have wondered: If it’s so hard for anything to get into the brain, how does waste get out? The brain has one of the highest metabolisms of any organ in the body, and that process must yield by-products that need to be removed. In the rest of the body, blood vessels are shadowed by a system of lymphatic vessels. Molecules that have served their purpose in the blood move into these fluid-filled tubes and are swept away to the lymph nodes for processing. But blood vessels in the brain have no such outlet. Several hundred kilometers of them, all told, seem to thread their way through this dense, busily working tissue without a matching waste system. However, the brain’s blood vessels are surrounded by open, fluid-filled spaces. In recent decades, the cerebrospinal fluid, or CSF, in those spaces has drawn a great deal of interest. “Maybe the CSF can be a highway, in a way, for the flow or exchange of different things within the brain,” said Steven Proulx, who studies the CSF system at the University of Bern. A recent paper in Cell contains a new report about what is going on around the brain (opens a new tab) and in its hidden cavities. A team at the University of Rochester led by the neurologist Maiken Nedergaard (opens a new tab) asked whether the slow pumping of the brain’s blood vessels might be able to push the fluid around, among, and in some cases through cells, to potentially drive a system of drainage. In a mouse model, researchers injected a glowing dye into CSF, manipulated the blood vessel walls to trigger a pumping action, and saw the dye concentration increase in the brain soon after. They concluded that the movement of blood vessels might be enough to move CSF, and possibly the brain’s waste, over long distances. © 2025 Simons Foundation.

First map of human brain mitochondria is ‘groundbreaking’ achievement

Nora Bradford Scientists have created the first map of the crucial structures called mitochondria throughout the entire brain ― a feat that could help to unravel age-related brain disorders1. The results show that mitochondria, which generate the energy that powers cells, differ in type and density in different parts of the brain. For example, the evolutionarily oldest brain regions have a lower density of mitochondria than newer regions. The map, which the study’s authors call the MitoBrainMap, is “both technically impressive and conceptually groundbreaking”, says Valentin Riedl, a neurobiologist at Friedrich-Alexander University in Erlangen, Germany, who was not involved in the project. The brain’s mitochondria are not just bit-part players. “The biology of the brain, we know now, is deeply intertwined with the energetics of the brain,” says Martin Picard, a psychobiologist at Columbia University in New York City, and a co-author of the study. And the brain accounts for 20% of the human body’s energy usage2. Wielding a tool typically used for woodworking, the study’s authors divided a slice of frozen human brain ― from a 54-year-old donor who died of a heart attack ― into 703 tiny cubes. Each cube measured 3 × 3 × 3 millimetres, which is comparable to the size of the units that make up standard 3D images of the brain. “The most challenging part was having so many samples,” says Picard. The team used biochemical and molecular techniques to determine the density of mitochondria in each of the 703 samples. In some samples, the researchers also estimated the mitochondria’s efficiency at producing energy. To extend their findings beyond a single brain slab, the authors developed a model to predict the numbers and types of mitochondria across the entire brain. They fed it brain-imaging data and the brain-cube data. To check their model, they applied it to other samples of the frozen brain slice and found that it accurately predicted the samples’ mitochondrial make-up. © 2025 Springer Nature

New brain scan method could help people with drug-resistant epilepsy

Anna Bawden Health and social affairs correspondent Researchers have developed ultra-powerful scans that could enable surgery for previously treatment-resistant epilepsy. Globally, about 50 million people have epilepsy. In England, epileptic seizures are the sixth most common reason for hospital admission. About 360,000 people in the UK have focal epilepsy, which causes recurring seizures in a specific part of the brain. Many patients successfully treat their condition with medication but for more than 100,000 patients, their symptoms do not improve with drugs, leaving surgery as the only option. Finding brain lesions, a significant cause of epilepsy, can be tricky. Ultra-powerful MRI scanners are capable of identifying even tiny lesions in patients’ brains. These 7T MRI scanners produce much more detailed resolution on brain scans, enabling better detection of lesions. If surgeons can see the lesions on MRI scans, this can double the chances of the patient being free of seizures after surgery. But 7T scanners are also susceptible to “dark patches” known as signal dropouts. Now researchers in Cambridge and Paris have developed a new technique to overcome the problem. Scientists at the University of Cambridge’s Wolfson Brain Imaging Centre, and the Université Paris-Saclay, used eight transmitters around the brain, rather than the usual one, to “parallel transmit” MRI images, which significantly reduced the number of black spots. The first study to use this approach, doctors at Addenbrooke’s hospital, Cambridge, then trialled the technique with 31 drug-resistant epilepsy patients to see whether the parallel transmit 7T scanner was better than conventional 3T scanners at detecting brain lesions. The research, published in the journal Epilepsia, found that the parallel transmit 7T scanner identified previously unseen structural lesions in nine patients. © 2025 Guardian News & Media Limited

Vesuvius Turned One Victim’s Brain to Glass

Five years ago Italian researchers published a study on the eruption of Mount Vesuvius in A.D. 79. that detailed how one victim of the blast, a male presumed to be in his mid 20s, had been found nearby in the seaside settlement of Herculaneum. He was lying facedown and buried by ash on a wooden bed in the College of the Augustales, a public building dedicated to the worship of Emperor Augustus. Some scholars believe that the man was the center’s caretaker and was asleep at the time of the disaster. In 2018, one researcher discovered black, glossy shards embedded inside the caretaker’s skull. The paper, published in 2020, speculated that the heat of the explosion was so immense that it had fused the victim’s brain tissue into glass. Vesuvius Erupted, but When Exactly? March 2, 2025 Forensic analysis of the obsidian-like chips revealed proteins common in brain tissue and fatty acids found in human hair, while a chunk of charred wood unearthed near the skeleton indicated a thermal reading as high as 968 degrees Fahrenheit, roughly the dome temperature of a wood-fired Neapolitan pizza oven. It was the only known instance of soft tissue — much less any organic material — being naturally preserved as glass. On Thursday, a paper published in Nature verified that the fragments are indeed glassified brain. Using techniques such as electron microscopy, energy dispersive X-ray spectroscopy and differential scanning calorimetry, scientists examined the physical properties of samples taken from the glassy fragments and demonstrated how they were formed and preserved. “The unique finding implies unique processes,” said Guido Giordano, a volcanologist at the Roma Tre University and lead author of the new study. Foremost among those processes is vitrification, by which material is burned at a high heat until it liquefies. To harden into glass, the substance requires rapid cooling, solidifying at a temperature higher than its surroundings. This makes organic glass formation challenging, Dr. Giordano said, as vitrification entails very specific temperature conditions and the liquid form must cool fast enough to avoid being crystallized as it congeals. © 2025 The New York Times Company

Cell ‘fingerprints’ identify distinct cortical networks

By Holly Barker Hunched over a microscope more than a century ago, Santiago Ramón y Cajal discovered that distinct types of neurons favor different brain regions. Looking at tissue from a pigeon’s cerebellum, he drew Purkinje cells, their dendrites outspread and twisted like a ravaged oak. And drawing from another sample—the first cortical layer of a newborn rabbit’s brain—he traced the tentacled nerve cells that would later bear his name. But the brain’s cellular organization is even more ordered than Ramón y Cajal could have imagined, a new study suggests. Different functional networks—measured using functional MRI—involve distinct blends of cell types, identified from their transcriptional profiles. And a machine-learning tool trained on cell distributions in postmortem tissue can identify functional networks based on these cellular “fingerprints,” the researchers found. The findings could address the gulf between neuroimaging and cell-based research, says the study’s principal investigator, Avram Holmes, associate professor of psychiatry at Rutgers University. “In-vivo imaging studies are almost never linked back to the underlying biological cascades that give rise to the phenotypes,” he says. But the new approach “lets you jump between fields of study—that was very difficult to do in the past.” Using bulk gene-expression data from postmortem human brain tissue—obtained from the Allen Human Brain Atlas—Holmes and his colleagues classified 24 different types of cells. They then mapped the cells’ spatial distribution to two features of large-scale brain organization derived from a popular fMRI atlas: networks, and those networks’ position in the cortical gradient, which is based on location, style of information processing and connectivity pattern. Unimodal sensorimotor networks—those that perceive stimuli and act on them—anchor one end of the gradient, and the other end is occupied by transmodal systems, such as the default mode network, that integrate multiple information streams across the cortex. The remaining networks are parked between these two extremes. © 2025 Simons Foundation

This drawing is the oldest known sketch of an insect brain

By Tina Hesman Saey After nearly 350 years, a depiction of a bee’s brain is getting some buzz. A manuscript created in the mid-1670s contains the oldest known depiction of an insect’s brain, historian of science Andrea Strazzoni of the University of Turin in Italy reports January 29 in Royal Society Notes and Records. Handwritten by Dutch biologist and microscopist Johannes Swammerdam, the manuscript contains a detailed description and drawing of a honeybee drone’s brain. The illustration, based on his own dissections, was just one of Swammerdam’s firsts. In 1658, he was also the first to see and describe red blood cells. Since no one had previously reported dissecting a bee brain, Swammerdam based his descriptions on what was known about the brain anatomy of humans and other mammals. “He knew what to expect from or to imagine in his observations: in particular, the pineal gland and the cerebellum,” Strazzoni writes. Bees have neither of those parts but have brain structures that the 17th century scientist mistook for them. But Swammerdam deserves some slack, Strazzoni suggests. He was working with single-lens microscopes and developing new techniques for dissecting and observing insects’ internal organs. Even with those crude instruments, he was able to identify some nerves and describe how parts of the brain connected. © Society for Science & the Public 2000–2025.

Related chapters from BN: Chapter 2: Functional Neuroanatomy: The Cells and Structure of the Nervous System; Chapter 6: Evolution of the Brain and Behavior
Related chapters from MM:Chapter 2: Neurophysiology: The Generation, Transmission, and Integration of Neural Signals
Link ID: 29644 - Posted: 01.29.2025

Digitization of ‘breathtaking’ neuroanatomy slide collection offers untapped research gold mine

By Shaena Montanari For evolutionary neuroanatomists who compare diverse animal brains, access to a gold mine of 500,000 histological sections and whole mounts is now only a mouse-click away. The R. Glenn Northcutt Collection of Comparative Vertebrate Neuroanatomy and Embryology at Harvard University—which comprises 33,000 slides of tissue samples from more than 240 vertebrate genera—is one of the world’s largest and most diverse collections of its kind. Northcutt, a prolific comparative vertebrate neuroanatomist and emeritus professor of neurosciences at the University of California, San Diego, amassed the collection over the course of five decades. Since 2021, James Hanken, research professor of biology at Harvard University and curator at the Museum of Comparative Zoology, has led an effort to digitize it. The scanning process is still ongoing and may take another two years to complete, Hanken says, but more than 8,000 slides are already publicly available in two online data repositories: MCZBase and MorphoSource. A comprehensive inventory of the entire collection appears in a paper Hanken and his colleagues published last week in the Bulletin of the Museum of Comparative Zoology. It provides researchers with an in-depth guide for using the collection, Hanken says. Few other resources of this type are available online to researchers interested in evolutionary biology and brain anatomy, says Andrew Iwaniuk, professor of neuroscience at the University of Lethbridge. For example, neither the Welker Comparative Anatomy Collection nor the Starr Collection, both housed at the U.S. National Museum of Health and Medicine in Silver Spring, Maryland, are available online. To access slide collections such as these, scientists have had to travel to see them in person, which can be difficult for those outside the United States, Iwaniuk adds. © 2025 Simons Foundation

Cambridge study aims to find out if dogs and their owners are on same wavelength

Nicola Davis Science correspondent Standing patiently on a small fluffy rug, Calisto the flat-coated retriever is being fitted with some hi-tech headwear. But this is not a new craze in canine fashion: she is about to have her brainwaves recorded. Calisto is one of about 40 pet dogs – from newfoundlands to Tibetan terriers – taking part in a study to explore whether their brainwaves synchronise with those of their owners when the pair interact, a phenomenon previously seen when two humans engage with each other. The researchers behind the work say such synchronisation would suggest person and pet are paying attention to the same things, and in certain circumstances interpreting moments in a similar way. In other words, owner and dog really are on the same wavelength. Dr Valdas Noreika of Queen Mary, University of London said he got the idea for the study after working on similar experiments with mothers and their babies, where such synchronisation has also been seen. “Owners modulate their language in a similar way as parents modulate when they speak to children,” he said. “There are lots of similarities. That could be one of the reasons why we get so attached to dogs – because we already have these cognitive functions and capacities to attach with someone who is smaller or requires help or attention.” Hints of an emotional bond between humans and their dogs stretch into the distant past: researchers have previously discovered the 14,000-year-old remains of a puppy buried in Germany alongside a man and a woman: the analysis suggested the young dog had been nursed through several periods of illness, despite having no particular use. © 2025 Guardian News & Media Limited o

Controversial study redraws classical picture of the neuron

' By Sofia Quaglia Flip open any neuroscience textbook and the depiction of a neuron will be roughly the same: a blobby, amoebalike cell body shooting out a long, thick strand. That strand is the axon, which conducts electrical signals to terminals where the cell communicates with other neurons. Axons have long been depicted as smooth and cylindrical, but a new study of mouse neurons challenges that view. Instead, it suggests their natural shape is more like a string of pearls. Even more provocatively, the authors propose those pearly bumps serve as control knobs, influencing how quickly and precisely the cell fires its signals. The study, published today in Nature Neuroscience, should “100%” change how we’ve been thinking about neurons and their signals, says senior author Shigeki Watanabe, a molecular neuroscientist at John Hopkins University. Some outsiders agree. The findings are “highly significant and I think have been overlooked for quite some time,” says evolutionary biologist Pawel Burkhardt of the University of Bergen, who recently spotted similar pearl structures in neurons from tiny marine invertebrates known as comb jellies. Yet several experts in the field contest the findings. Some cite potential confounding effects of the preparation and freezing method used to preserve cells before imaging. And some doubt the work totally upends what’s known about the true shape of the axon. “I think it’s true that [the axon is] not a perfect tube, but it’s not also just this kind of accordion that they show,” says neuroscientist Christophe Leterrier from Aix-Marseille University, who calls the study “a controversial addition to the literature.” Since the mid-1960s, microscopists have seen that axons can scrunch up to form beads when they are diseased or under other stress. Leterrier has called these temporary beads “stress balls for the brain” and found evidence that they prevent cellular damage from spreading. Other studies suggest even normal axons bulge temporarily when cargo traveling to and from the cell nucleus forms a traffic jam, like the elephant bulging inside the body of a boa in the children’s book The Little Prince.

Largest brain map ever reveals fruit fly’s neurons in exquisite detail

By Sara Reardon Researchers have mapped nearly 140,000 neurons in the fruit-fly brain. This version shows the 50 largest. Credit: Tyler Sloan and Amy Sterling for FlyWire, Princeton University (ref. 1) A fruit fly might not be the smartest organism, but scientists can still learn a lot from its brain. Researchers are hoping to do that now that they have a new map — the most complete for any organism so far — of the brain of a single fruit fly (Drosophila melanogaster). The wiring diagram, or ‘connectome’, includes nearly 140,000 neurons and captures more than 54.5 million synapses, which are the connections between nerve cells. “This is a huge deal,” says Clay Reid, a neurobiologist at the Allen Institute for Brain Science in Seattle, Washington, who was not involved in the project but has worked with one of the team members who was. “It’s something that the world has been anxiously waiting for, for a long time.” The map1 is described in a package of nine papers about the data published in Nature today. Its creators are part of a consortium known as FlyWire, co-led by neuroscientists Mala Murthy and Sebastian Seung at Princeton University in New Jersey. Seung and Murthy say that they’ve been developing the FlyWire map for more than four years, using electron microscopy images of slices of the fly’s brain. The researchers and their colleagues stitched the data together to form a full map of the brain with the help of artificial-intelligence (AI) tools. But these tools aren’t perfect, and the wiring diagram needed to be checked for errors. The scientists spent a great deal of time manually proofreading the data — so much time that they invited volunteers to help. In all, the consortium members and the volunteers made more than three million manual edits, according to co-author Gregory Jefferis, a neuroscientist at the University of Cambridge, UK. (He notes that much of this work took place in 2020, when fly researchers were at loose ends and working from home during the COVID-19 pandemic.) © 2024 Springer Nature Limited

Brain imaging at the fair with Ka Ip

By Angie Voyles Askham Most people visit the Minnesota State Fair for a fun-filled day of fried food, farm animals and carnival rides. Not Ka Ip. He saw the annual event as the perfect setting for a new experiment. Ip, assistant professor of child development at the University of Minnesota, is particularly interested in executive function: the set of skills, such as organization and impulse control, people need to plan and achieve goals. Children from lower socioeconomic backgrounds tend to perform worse on tests of these skills than do their more privileged peers, past research shows. But that gap may reflect where those skills are typically tested: a quiet lab, in which some children may feel out of their element, Ip says. “That may not actually mimic their actual day-to-day environment.” Which is why Ip started to devise a series of experiments to conduct at the less-than-serene state fair. “We really want to understand how, for example, unpredictability in the home environment is related to executive function development,” he says. The fair also offered a way to recruit children from a wider swath of society than researchers can often find at a university, he adds. Last month, after a year of planning, Ip and his team lugged a trolley full of equipment to the fairgrounds outside Minneapolis. There, they collected functional near-infrared spectroscopy (fNIRS) data on 75 children aged 3 to 7 as they played a computer game that tests impulse control. The team aims to evaluate whether the bustling surroundings affect participants’ performances and neural activity differently based on their background. © 2024 Simons Foundation

AI met fruit fly, and a better brain model emerged

Jon Hamilton Scientists have created a virtual brain network that can predict the behavior of individual neurons in a living brain. The model is based on a fruit fly’s visual system, and it offers scientists a way to quickly test ideas on a computer before investing weeks or months in experiments involving actual flies or other lab animals. “Now we can start with a guess for how the fly brain might work before anyone has to make an experimental measurement,” says Srini Turaga, a group leader at the Janelia Research Campus, a part of the Howard Hughes Medical Institute (HHMI). The approach, described in the journal Nature, also suggests that power-hungry artificial intelligence systems like ChatGPT might consume much less energy if they used some of the computational strategies found in a living brain. A fruit fly brain is “small and energy efficient,” says Jakob Macke, a professor at the University of Tübingen and an author of the study. “It’s able to do so many computations. It’s able to fly, it’s able to walk, it’s able to detect predators, it’s able to mate, it’s able to survive—using just 100,000 neurons.” In contrast, AI systems typically require computers with tens of billions of transistors. Worldwide, these systems consume as much power as a small country. “When we think about AI right now, the leading charge is to make these systems more power efficient,” says Ben Crowley, a computational neuroscientist at Cold Spring Harbor Laboratory who was not involved in the study. Borrowing strategies from the fruit fly brain might be one way to make that happen, he says. © 2024 npr

Brain fluid may travel to distant parts of body

By Rodrigo Pérez Ortega Names can be deceiving. One might think “cerebrospinal fluid” only lives in the brain and spinal cord. Indeed, that’s what scientists and doctors have largely believed for centuries. But the clear liquid—which cleans, feeds, and protects the organs it surrounds—also bathes the body’s nerves, researchers report today in Science Advances. “This is one of the [most] important papers in this area,” says Karl Bechter, a clinical neurologist at Ulm University who was not involved in the study. In the past, he and others have suggested instances in which cerebrospinal fluid (CSF) permeates nerves, but he says this is the first study that shows it can travel far throughout the body. The finding could open new ways to deliver drugs to some of the most inaccessible parts of the body. The human body is a bundle of nerves. Besides the head honchos that make up the central nervous system—the brain and spinal cord—kilometers of spindly fibers snake their way throughout our anatomy. Here, they form a peripheral nervous system that fires the signals that allow us to do everything from walking to feeling pain. Yet even though the two systems interface, previous anatomy studies indicated CSF was restricted to the central nervous system. Things changed 2.5 years ago when Edward Scott, a stem cell biologist at the University of Florida, and his surgeon colleague Joe Pessa noticed something strange during a plastic surgery study. Pessa was researching ways to avoid damaging CSF-containing structures and nerves during surgical procedures. When the scientists injected saline into the brain chambers of human cadavers that contained CSF, a peripheral nerve in the wrist swelled up. They then decided to explore further, injecting a fluorescent liquid in live mice’s brain chambers to track where the liquid went. The dye somehow made its way to the sciatic nerve, which runs throughout the back of the leg. Intrigued, the team decided to repeat the experiment in mice using a much finer tracer: nanoparticles of gold. These tiny particles can be detected through both light and electron microscopy and can be tailored to specific sizes.

Neurons’ spikes may convey their whereabouts

By Holly Barker Machine-learning models can predict a neuron’s location based on recorded bursts of activity, a new preprint suggests. The findings may provide novel insights into how the brain integrates signals from different regions, the researchers say. The algorithm—trained on electrode recordings of neurons in mice—appeared to learn a cell’s whereabouts from its interspike interval, the sequence of delays between blips of activity. And after deciphering the spike pattern from one mouse, the tool predicted neuronal locations based on recordings from another rodent. That conservation between animals suggests the information serves some useful brain function, or at least doesn’t get in the way, says lead investigator Keith Hengen, assistant professor of biology at Washington University in St. Louis. Although more research is needed, the anatomical information embedded in interspike intervals could—in theory—provide contextual information for neuronal computations. For example, the brain might process signals from thalamic neurons differently from those in the hippocampus, says study investigator Aidan Schneider, a graduate student in Hengen’s lab. Schneider and his colleagues trained the model using tens of thousands of Neuropixels probe recordings from 58 awake mice, published by the Allen Institute. When Schneider’s team presented the algorithm with fresh data, it could decipher whether a given neuron resided in the hippocampus, midbrain, thalamus or visual cortex 89 percent of the time, once the team removed noise from the data. (Random guesses would be correct 25 percent of the time.) But the tool was less able to pinpoint specific substructures within those regions. It’s a great example of the kinds of insights that labs poring over huge datasets can produce, says Drew Headley, assistant professor of molecular and behavioral neuroscience at Rutgers University, who was not involved in the study. But the findings may simply echo published reports of variations in spiking activity across different brain regions, he says. © 2024 Simons Foundation

Getting drugs into the brain is hard. Maybe a parasite can do the job

By Tina Hesman Saey A mind-bending parasite may one day deliver drugs to the brain. Toxoplasma gondii is a single-celled parasite that famously makes mice lose their fear of cats, but also can cause deadly foodborne illnesses (SN: 1/14/20). Now, researchers have engineered the parasite to deliver large therapeutic proteins to the brains of mice and into human brain cells grown in lab dishes, an international team of scientists reports July 29 in Nature Microbiology. Such proteins and the genes that produce them are often too big for viruses — the most common courier for gene therapy — to carry (SN: 10/20/23). If the parasite can be made safe for human use, the technique may eventually help treat a variety of neurological conditions. While critics doubt that the parasitic villain can ever be turned into a helpful hero, some researchers are intrigued by the idea. Microbes such as bacteria and parasites are usually viewed as bad guys, says Sara Molinari, a bacterial synthetic biologist at the University of Maryland in College Park who was not involved with the work. But microbes have evolved “pretty sophisticated relationships with our bodies,” she says. “The idea that we can leverage this relationship to instruct them to do good things for us is actually groundbreaking.” Current methods of delivering therapies to the brain often produce unpredictable results or have a hard time penetrating the protective shield known as the blood-brain barrier, says Shahar Bracha, a bioengineer and neuroscientist at MIT (SN: 5/2/23). © Society for Science & the Public 2000–2024.

New connectomes fly beyond the brain

By Laura Dattaro When John Tuthill was a postdoctoral researcher at Harvard Medical School, he worked just down the hall from Wei-Chung Allen Lee, who was developing new technology to image and map cell connections in the central nervous system. Lee wanted to use his technique in the fruit fly Drosophila, but he knew that other groups were already making such images of the fly brain. So Tuthill, who was studying touch stimuli in Drosophila, suggested Lee pivot to map the fly’s ventral nerve cord (VNC) instead. A decade later, Tuthill, Lee and colleagues have published a map of the connections among motor neurons in a female fly’s VNC, which is analogous to the spinal cord in mammals. The diagram, published on 26 June in Nature, details roughly 45 million synapses that connect nearly 15,000 neurons, and is the second such connectome to be released. A different team, at Howard Hughes Medical Institute’s Janelia Research Campus, published a male fly’s VNC connectome to eLife’s preprint server in June 2023. (The team posted an updated, reviewed preprint on 23 May 2024.) “The connectome is only useful if you can connect it to the muscles,” says Tuthill, associate professor of neuroscience at the University of Washington. “The output of the connectome is the activity of motor neurons.” With connectomes from both a male and a female fly, researchers are starting to look for differences not only between individuals, but between the sexes. An initial comparison of the two connectomes, posted to bioRxiv on 28 June by members of both teams, including Tuthill and Lee, identified circuits that appear to control sex-specific behaviors, including male courtship songs and the female extension of an organ used to deposit eggs. © 2024 Simons Foundation

To develop better nervous-system visualizations, we need to think BIG

By Tyler Sloan If I ask you to picture a group of “neurons firing,” what comes to mind? For most people, it’s a few isolated neurons flashing in synchrony. This type of minimalist representation of neurons is common within neuroscience, inspired in part by Santiago Ramón y Cajal’s elegant depictions of the nervous system. His work left a deep mark on our intuitions, but the method he used—Golgi staining—highlights just 1 to 5 percent of neurons. More than a century later, researchers have mapped out brain connectivity in such detail that it easily becomes overwhelming; I vividly recall an undergraduate neurophysiology lecture in which the professor showed a wiring diagram of the primary visual cortex to make the point that it was too complex to understand. We’ve reached a point where simple wiring diagrams no longer suffice to represent what we’re learning about the brain. Advances in experimental and computational neuroscience techniques have made it possible to map brains in more detail than ever before. The wiring diagram for the whole fly brain, for example, mapped at single-synapse resolution, comprises 2.7 million cell-to-cell connections and roughly 150 million synapses. Building an intuitive understanding of this type of complexity will require new tools for representing neural connectivity in a way that is both meaningful and compact. To do this, we will have to embrace the elaborate and move beyond the single neuron to a more “maximalist” approach to visualizing the nervous system. I spent my Ph.D. studying the spinal cord, where commissural growth cones are depicted as pioneers on a railhead extending through uncharted territory. The watershed moment for me was seeing a scanning electron micrograph of the developing spinal cord for the first time and suddenly understanding the growth cone’s dense environment—its path was more like squeezing through a crowded concert than wandering across an empty field. I realized how poor my own intuitions were, which nudged me toward learning the art of 3D visualization. © 2024 Simons Foundation

Big Brother of the Brain Is Here

By Adolfo Plasencia Recently, a group of Australian researchers demonstrated a “mind-reading” system called BrainGPT. The system can, according to its creators, convert thoughts (recorded with a non-invasive electrode helmet) into words that are displayed on a screen. Essentially, BrainGPT connects a multitasking EEG encoder to a large language model capable of decoding coherent and readable sentences from EEG signals. Is the mind, the last frontier of privacy, still a safe place to think one’s thoughts? I spoke with Harvard-based behavioral neurologist Alvaro Pascual-Leone, a leader in the study of neuroplasticity and noninvasive brain stimulation, about what it means and how we can protect ourselves. The reality is that the ability to read the brain and influence activity is already here. It’s no longer only in the realm of science fiction. Now, the question is, what exactly can we access and manipulate in the brain? Consider this example: If I instruct you to move a hand, I can tell if you are preparing to move, say, your right hand. I can even administer a precise “nudge” to your brain and make you move your right hand faster. And you would then claim, and fully believe, that you moved it yourself. However, I know that, in fact, it was me who moved it for you. I can even force you to move your left hand—which you were not going to move—and lead you to rationalize why you changed your mind when in fact, our intervention led to that action you perceive as your choice. We have done this experiment in our laboratory. In humans, we can modify brain activity by reading and writing in the brain, so to speak, though we can affect only very simple things right now. In animals, we can do much more complex things because we have much more precise control of the neurons and their timing. But the capacity for that modulation of smaller circuits progressively down to individual neurons in humans is going to come, including much more selective modification with optogenetic alternatives—that is, using light to control the activity of neurons. © 2024 NautilusNext Inc.,

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