Chapter 3. The Chemistry of Behavior: Neurotransmitters and Neuropharmacology

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By Yasemin Saplakoglu György Buzsáki first started tinkering with waves when he was in high school. In his childhood home in Hungary, he built a radio receiver, tuned it to various electromagnetic frequencies and used a radio transmitter to chat with strangers from the Faroe Islands to Jordan. He remembers some of these conversations from his “ham radio” days better than others, just as you remember only some experiences from your past. Now, as a professor of neuroscience at New York University, Buzsáki has moved on from radio waves to brain waves to ask: How does the brain decide what to remember? By studying electrical patterns in the brain, Buzsáki seeks to understand how our experiences are represented and saved as memories. New studies from his lab and others have suggested that the brain tags experiences worth remembering by repeatedly sending out sudden and powerful high-frequency brain waves. Known as “sharp wave ripples,” these waves, kicked up by the firing of many thousands of neurons within milliseconds of each other, are “like a fireworks show in the brain,” said Wannan Yang, a doctoral student in Buzsáki’s lab who led the new work, which was published in Science in March. They fire when the mammalian brain is at rest, whether during a break between tasks or during sleep. Sharp wave ripples were already known to be involved in consolidating memories or storing them. The new research shows that they’re also involved in selecting them — pointing to the importance of these waves throughout the process of long-term memory formation. It also provides neurological reasons why rest and sleep are important for retaining information. Resting and waking brains seem to run different programs: If you sleep all the time, you won’t form memories. If you’re awake all the time, you won’t form them either. “If you just run one algorithm, you will never learn anything,” Buzsáki said. “You have to have interruptions.” © 2024 the Simons Foundation.

Keyword: Learning & Memory
Link ID: 29322 - Posted: 05.23.2024

Ian Sample Science editor A device that stimulates the spinal nerves with electrical pulses appears to boost how well people recover from major spinal cord injuries, doctors say. An international trial found that patients who had lost some or all use of their hands and arms after a spinal cord injury regained strength, control and sensation when the stimulation was applied during standard rehabilitation exercises. The improvements were small but were described by doctors and patients as life-changing because of the impact they had on the patients’ daily routines and quality of life. “It actually makes it easier for people to move, including people who have complete loss of movement in their hands and arms,” said Prof Chet Moritz, in the department of rehabilitation medicine at the University of Washington in Seattle. “The benefits accumulate gradually over time as we pair this spinal stimulation with intensive therapy of the hands and arms, such that there are benefits even when the stimulator is turned off.” Rather than being implanted, the Arc-Ex device is worn externally and uses electrodes that are placed on the skin near the section of the spinal cord responsible for controlling a particular movement or function. The researchers believe that electrical stimulation helps nerves that remain intact after the injury to send signals and ultimately partially restore some communication between the brain and paralysed body part. More than half of patients who suffer spinal cord injuries still have some intact nerves that cross the injury site. © 2024 Guardian News & Media Limited

Keyword: Robotics; Movement Disorders
Link ID: 29315 - Posted: 05.21.2024

By Claudia López Lloreda As animals carry out complex behaviors, multiple brain areas turn on and talk to one another. But neuroscientists have had limited means to measure that neuronal dialogue. Electrical recordings, for example, are typically constrained to one brain area at a time, or require that mice have their head fixed in a specific position. A new technology overcomes those restrictions. The device, called E-Scope, reported in a peer-reviewed preprint in eLife, effectively measures the activity of neurons in two different areas at the same time, even as rodents move freely. The headset captures images of calcium currents, made using a microscope, and recordings of neurons’ electrical activity through electrodes to show how the cerebellum communicates with other brain regions during social interaction in mice. “Everything [is] synchronized together that way,” says Peyman Golshani, assistant professor of neurology at the University of California, Los Angeles and a study investigator. This approach holds the potential to illuminate how coordination between brain areas in conditions marked by impaired social interaction, such as attention-deficit/hyperactivity disorder and autism, is disrupted, Golshani says. By combining technologies, researchers who use the E-Scope “don’t need separate electrophysiology and imaging hardware,” he adds. It’s also much more comfortable for the animals, according to Golshani. A single wire conveys all of the small headset’s data, so mice can move more freely than when wearing other devices. © 2024 Simons Foundation

Keyword: Brain imaging
Link ID: 29244 - Posted: 04.06.2024

By Javier C. Hernández The pianist Alice Sara Ott, barefoot and wearing a silver bracelet, was smiling and singing to herself the other day as she practiced a jazzy passage of Ravel at Steinway Hall in Midtown Manhattan. A Nintendo Switch, which she uses to warm up her hands, was by her side (another favored tool is a Rubik’s Cube). A shot of espresso sat untouched on the floor. “I feel I have finally found my voice,” Ott said during a break. “I feel I can finally be myself.” Ott, 35, who makes her New York Philharmonic debut this week, has built a global career, recording more than a dozen albums and appearing with top ensembles. She has become a force for change in classical music, embracing new approaches (playing Chopin on beat-up pianos in Iceland) and railing against stuffy concert culture (she performs without shoes, finding it more comfortable). And Ott, who lives in Munich and has roots in Germany and Japan, has done so while grappling with illness. In 2019, when she was 30, she was diagnosed with multiple sclerosis. She says she has not shown any symptoms since starting treatment, but the disorder has made her reflect on the music industry’s grueling work culture. “I learned to accept that there is a limit and to not go beyond that,” she said. “Everybody knows how to ignore their body and just go on. But there’s always a payback.” Ott has used her platform to help dispel myths about multiple sclerosis, a disorder of the central nervous system that can cause a wide range of symptoms, including muscle spasms, numbness and vision problems. She has taken to social media to detail her struggles and to challenge those who have suggested that the illness has affected her playing. She said she felt she had no choice but to be transparent, saying it was important to show that people with multiple sclerosis could lead full lives. “I don’t consider it as a weakness,” she said. “It’s a fact. I live with it. And I don’t want to make a big drama out of it.” © 2024 The New York Times Company

Keyword: Multiple Sclerosis
Link ID: 29237 - Posted: 04.04.2024

by Alex Blasdel Patient One was 24 years old and pregnant with her third child when she was taken off life support. It was 2014. A couple of years earlier, she had been diagnosed with a disorder that caused an irregular heartbeat, and during her two previous pregnancies she had suffered seizures and faintings. Four weeks into her third pregnancy, she collapsed on the floor of her home. Her mother, who was with her, called 911. By the time an ambulance arrived, Patient One had been unconscious for more than 10 minutes. Paramedics found that her heart had stopped. After being driven to a hospital where she couldn’t be treated, Patient One was taken to the emergency department at the University of Michigan. There, medical staff had to shock her chest three times with a defibrillator before they could restart her heart. She was placed on an external ventilator and pacemaker, and transferred to the neurointensive care unit, where doctors monitored her brain activity. She was unresponsive to external stimuli, and had a massive swelling in her brain. After she lay in a deep coma for three days, her family decided it was best to take her off life support. It was at that point – after her oxygen was turned off and nurses pulled the breathing tube from her throat – that Patient One became one of the most intriguing scientific subjects in recent history. For several years, Jimo Borjigin, a professor of neurology at the University of Michigan, had been troubled by the question of what happens to us when we die. She had read about the near-death experiences of certain cardiac-arrest survivors who had undergone extraordinary psychic journeys before being resuscitated. Sometimes, these people reported travelling outside of their bodies towards overwhelming sources of light where they were greeted by dead relatives. Others spoke of coming to a new understanding of their lives, or encountering beings of profound goodness. Borjigin didn’t believe the content of those stories was true – she didn’t think the souls of dying people actually travelled to an afterworld – but she suspected something very real was happening in those patients’ brains. In her own laboratory, she had discovered that rats undergo a dramatic storm of many neurotransmitters, including serotonin and dopamine, after their hearts stop and their brains lose oxygen. She wondered if humans’ near-death experiences might spring from a similar phenomenon, and if it was occurring even in people who couldn’t be revived. © 2024 Guardian News & Media Limited

Keyword: Consciousness; Attention
Link ID: 29236 - Posted: 04.02.2024

Andrew Gregory Health editor Previous evidence has suggested a link between high body mass index (BMI) in adolescence and an increased risk of MS. But most of these studies were retrospective in design and used self-reported data. Researchers involved with the new study sought to prospectively evaluate the risk of developing MS in a large cohort of obese children compared with the general population. Academics analysed data from the Swedish Childhood Obesity Treatment Register. The database, known as Boris, is one of the world’s largest registries for treatment of childhood obesity. The research team looked at data on children aged two to 19 who joined the registry between 1995 and 2020, and compared their information with that of children in the general population. The study included data on more than 21,600 children with obesity, who started treatment for obesity when they were an average age of 11, and more than 100,000 children without obesity. Children involved in the study were tracked for an average of six years. During the follow-up period, MS was diagnosed in 28 of those with obesity (0.13% of the group) and 58 in the group without obesity (0.06%). © 2024 Guardian News & Media Limite

Keyword: Multiple Sclerosis; Obesity
Link ID: 29224 - Posted: 03.30.2024

By Elizabeth Landau Electroconvulsive therapy has a public relations problem. The treatment, which sends electric currents through the brain to induce a brief seizure, has barbaric, inhumane connotations — for example, it was portrayed as a sadistic punishment in the film One Flew Over the Cuckoo’s Nest. But for patients with depression that does not improve with medications, electroconvulsive therapy (ECT) can be highly effective. Studies have found that some 50% to 70% of patients with major depressive disorder see their symptoms improve after a course of ECT. In comparison, medications aimed at altering brain chemistry help only 10% to 40% of depression patients. Still, even after many decades of use, scientists don’t know how ECT alters the brain’s underlying biology. Bradley Voytek, a neuroscientist at the University of California, San Diego, said a psychiatrist once told him that the therapy “reboots the brain” — an explanation he found “really unsatisfying.” Recently, Voytek and his collaborators paired their research into the brain’s electrical patterns with patient data to explore why inducing seizures has antidepressant effects. In two studies published last fall, the researchers observed that ECT and a related seizure therapy increased the unstructured background noise hiding behind well-defined brain waves. Neuroscientists call this background noise “aperiodic activity.” The authors suggested that induced seizures might help restore the brain’s balance of excitation and inhibition, which could have an overall antidepressant effect. “Every time that I talk to someone who’s not in this field about this work they’re like, ‘They still do that? They still use electroshock? I thought that was just in horror movies,’” said Sydney Smith, a graduate student in neuroscience in Voytek’s lab and the first author of the new studies. “Dealing with the stigma around it has become even more of a motivation to figure out how it works.” © 2024 Simons Foundation.

Keyword: Depression; Attention
Link ID: 29199 - Posted: 03.19.2024

By Tina Hesman Saey One particular retrovirus — embedded in the DNA of jawed vertebrates — helps turn on production of a protein needed to insulate nerve fibers, researchers report February 15 in Cell. Such insulation, called myelin, may have helped make speedy thoughts and complex brains possible. The retrovirus trick was so handy, in fact, that it showed up many times in the evolution of vertebrates with jaws, the team found. Retroviruses — also known as jumping genes or retrotransposons — are RNA viruses that make DNA copies of themselves to embed in a host’s DNA. Scientists once thought of remnants of ancient viruses as genetic garbage, but that impression is changing, says neuroscientist Jason Shepherd, who was not involved in the study. “We’re finding more and more that these retrotransposons and retroviruses have influenced the evolution of life on the planet,” says Shepherd, of the University of Utah Spencer Fox Eccles School of Medicine in Salt Lake City. Remains of retroviruses were already known to have aided the evolution of the placenta, the immune system and other important milestones in human evolution (SN: 5/16/17). Now, they’re implicated in helping to produce myelin. Myelin is a coating of fat and protein that encases long nerve fibers known as axons. The coating works a bit like the insulation around an electrical wire: Nerves sheathed in myelin can send electrical signals faster than uninsulated nerves can. © Society for Science & the Public 2000–2024.

Keyword: Glia; Evolution
Link ID: 29154 - Posted: 02.20.2024

By Jyoti Madhusoodanan On July 12, 2015, Elena Daly was packing for a family vacation when she walked into her 16-year-old son’s room and found him unconscious. Her son, Max, had overdosed on opioids, aspirated vomit, and fallen into a coma. By that point, Max had struggled with addiction for about three years. He had tried medication, therapy, and residential treatment programs in France, where the family lives, as well as in the United States and the United Kingdom. In fact, his July relapse occurred just days after returning home from a six-month stint in an in-patient rehab program. The coma lasted three days and worsened a pre-existing movement disorder to a degree where Max was unable to attend high school. “I couldn’t hold a pen without throwing it across the room or hold a cup of coffee without spilling it on myself,” he recently recalled. Max’s struggles with opioid use are not unusual: An estimated 40 to 60 percent of people who have an addiction experience relapse after treatment. Some researchers have suggested that a substantial portion of those who relapse suffer from what might be considered a “treatment-resistant” form of the disorder, though that condition is not formally recognized as a medical diagnosis. In recent years, scientists have explored treating these intractable cases of opioid dependence with deep brain stimulation, an intervention that entails surgically implanting an electrode into a precisely determined region of the brain, where it delivers regular pulses to control problematic electric signals. The surgery has proven effective for neurological conditions such as Parkinson’s disease and essential tremor, a disorder that can cause a person’s limbs, head, trunk, and voice to quake. But for researchers attempting to study its efficacy for addiction, the procedure’s invasiveness and cost — typically in the hundreds of thousands of dollars — have raised steep hurdles. Work in the field has largely been limited to one-off treatments and small studies with one or a few participants, making it tough to ascertain how many people globally have received the treatment or how successful it has been for them.

Keyword: Drug Abuse
Link ID: 29121 - Posted: 01.31.2024

By Carl Zimmer Multiple sclerosis, an autoimmune disease that affects 2.9 million people, presents a biological puzzle. Many researchers suspect that the disease is triggered by a virus, known as Epstein-Barr, which causes the immune system to attack the nerves and can leave patients struggling to walk or talk. But the virus can’t be the whole story, since nearly everyone is infected with it at some point in life. A new study found a possible solution to this paradox in the skeletal remains of a lost tribe of nomads who herded cattle across the steppes of western Asia 5,000 years ago. It turns out that the nomads carried genetic mutations that most likely protected them from pathogens carried by their animals, but that also made their immune systems more sensitive. These genes, the study suggests, made the nomads’ descendants prone to a runaway immune response. The finding is part of a larger, unprecedented effort to understand how the evolutionary past has shaped the health of living people. Researchers are analyzing thousands of genomes of people who lived between Portugal and Siberia and between Norway and Iran roughly 3,000 to 11,000 years ago. They hope to trace the genetic roots of not only multiple sclerosis, but also diabetes, schizophrenia and many other modern illnesses. “We are taking ancient human genomics to a whole new level,” said Eske Willerslev, a geneticist at the University of Copenhagen who led the effort. The researchers published the multiple sclerosis study as well as three other papers on the genetics and health of ancient peoples on Wednesday in the journal Nature. For more than a decade, Dr. Willerslev and other researchers have been pulling DNA from ancient human bones. By comparing the surviving genetic material with that of living people, the scientists have been able to track some of the most significant migrations of people across the world. © 2024 The New York Times Company

Keyword: Multiple Sclerosis; Evolution
Link ID: 29093 - Posted: 01.11.2024

Kamal Nahas Peter Hegemann, a biophysicist at Humboldt University, has spent his career exploring interactions between proteins and light. Specifically, he studies how photoreceptors detect and respond to light, focusing largely on rhodopsins, a family of membrane photoreceptors in animals, plants, fungi, protists, and prokaryotes.1 Early in his career, his curiosity led him to an unknown rhodopsin in green algae that later proved to have useful applications in neuroscience research. Hegemann became a pioneer in the field of optogenetics, which revolutionized the ways in which scientists draw causal links between neuronal activity and behavior. In the early 1980s during his graduate studies at the Max Planck Institute of Biochemistry, Hegemann spent his days exploring rhodopsins in bacteria and archaea. However, the field was crowded, and he was eager to study a rhodopsin that scientists knew nothing about. Around this time, Kenneth Foster, a biophysicist at Syracuse University, was investigating whether the green algae Chlamydomonas, a photosynthetic unicellular eukaryote related to plants, used a rhodopsin in its eyespot organelle to detect light and trigger the algae to swim. He struggled to pinpoint the protein itself, so he took a roundabout approach and started interfering with nearby molecules that interact with rhodopsins.2 Rhodopsins require the small molecule retinal to function as a photoreceptor. When Foster depleted Chlamydomonas of its own retinal, the algae were unable to use light to direct movement, a behavior that was restored when he introduced retinal analogues. In 1985, Hegemann joined Foster’s group as a postdoctoral researcher to continue this work. “I wanted to find something new,” Hegemann said. “Therefore, I worked on an exotic organism and an exotic topic.” A year later, Hegemann started his own research group at the Max Planck Institute of Biochemistry where he searched for the green algae’s rhodopsin that Foster proposed should exist. © 1986–2024 The Scientist.

Keyword: Brain imaging; Vision
Link ID: 29077 - Posted: 01.03.2024

Sydney E. Smith When most people hear about electroconvulsive therapy, or ECT, it typically conjures terrifying images of cruel, outdated and pseudo-medical procedures. Formerly known as electroshock therapy, this perception of ECT as dangerous and ineffective has been reinforced in pop culture for decades – think the 1962 novel-turned-Oscar-winning film “One Flew Over the Cuckoo’s Nest,” where an unruly patient is subjected to ECT as punishment by a tyrannical nurse. Despite this stigma, ECT is a highly effective treatment for depression – up to 80% of patients experience at least a 50% reduction in symptom severity. For one of the most disabling illnesses around the world, I think it’s surprising that ECT is rarely used to treat depression. Contributing to the stigma around ECT, psychiatrists still don’t know exactly how it heals a depressed person’s brain. ECT involves using highly controlled doses of electricity to induce a brief seizure under anesthesia. Often, the best description you’ll hear from a physician on why that brief seizure can alleviate depression symptoms is that ECT “resets” the brain – an answer that can be fuzzy and unsettling to some. As a data-obsessed neuroscientist, I was also dissatisfied with this explanation. In our newly published research, my colleagues and I in the lab of Bradley Voytek at UC San Diego discovered that ECT might work by resetting the brain’s electrical background noise. To study how ECT treats depression, my team and I used a device called an electroencephalogram, or EEG. It measures the brain’s electrical activity – or brain waves – via electrodes placed on the scalp. You can think of brain waves as music played by an orchestra. Orchestral music is the sum of many instruments together, much like EEG readings are the sum of the electrical activity of millions of brain cells. © 2010–2023, The Conversation US, Inc.

Keyword: Depression
Link ID: 29036 - Posted: 12.09.2023

By Carl Zimmer Traumatic brain injuries have left more than five million Americans permanently disabled. They have trouble focusing on even simple tasks and often have to quit jobs or drop out of school. A study published on Monday has offered them a glimpse of hope. Five people with moderate to severe brain injuries had electrodes implanted in their heads. As the electrodes stimulated their brains, their performance on cognitive tests improved. If the results hold up in larger clinical trials, the implants could become the first effective therapy for chronic brain injuries, the researchers said. “This is the first evidence that you can move the dial for this problem,” said Dr. Nicholas Schiff, a neurologist at Weill Cornell Medicine in New York who led the study. Gina Arata, one of the volunteers who received the implant, was 22 when a car crash left her with fatigue, memory problems and uncontrollable emotions. She abandoned her plans for law school and lived with her parents in Modesto, Calif., unable to keep down a job. In 2018, 18 years after the crash, Ms. Arata received the implant. Her life has changed profoundly, she said. “I can be a normal human being and have a conversation,” she said. “It’s kind of amazing how I’ve seen myself improve.” Dr. Schiff and his colleagues designed the trial based on years of research on the structure of the brain. Those studies suggested that our ability to focus on tasks depends on a network of brain regions that are linked to each other by long branches of neurons. The regions send signals to each other, creating a feedback loop that keeps the whole network active. Sudden jostling of the brain — in a car crash or a fall, for example — can break some of the long-distance connections in the network and lead people to fall into a coma, Dr. Schiff and his colleagues have hypothesized. During recovery, the network may be able to power itself back up. But if the brain is severely damaged, it may not fully rebound. Dr. Schiff and his colleagues pinpointed a structure deep inside the brain as a crucial hub in the network. Known as the central lateral nucleus, it is a thin sheet of neurons about the size and shape of an almond shell. © 2023 The New York Times Company

Keyword: Brain Injury/Concussion
Link ID: 29033 - Posted: 12.06.2023

By Simon Makin Our thoughts and feelings arise from networks of neurons, brain cells that send signals using chemicals called neurotransmitters. But neurons aren't alone. They're supported by other cells called glia (Greek for “glue”), which were once thought to hold nerve tissue together. Today glia are known to help regulate metabolism, protect neurons and clean up cellular waste—critical but unglamorous roles. Now, however, neuroscientists have discovered a type of “hybrid” glia that sends signals using glutamate, the brain's most common neurotransmitter. These findings, published in Nature, breach the rigid divide between signaling neurons and supportive glia. “I hope it's a boost for the field to move forward, to maybe begin studying why certain [brain] circuits have this input and others don't,” says study co-author Andrea Volterra, a neuroscientist at the University of Lausanne in Switzerland. Around 30 years ago researchers began reporting that star-shaped glia called astrocytes could communicate with neurons. The idea was controversial, and further research produced contradictory results. To resolve the debate, Volterra and his team analyzed existing data from mouse brains. These data were gathered using a technique called single-cell RNA sequencing, which lets researchers catalog individual cells' molecular profiles instead of averaging them in a bulk tissue sample. Of nine types of astrocytes they found in the hippocampus—a key memory region—one had the cellular machinery required to send glutamate signals. The small numbers of these cells, present only in certain regions, may explain why earlier research missed them. “It's quite convincing,” says neuroscientist Nicola Hamilton-Whitaker of King's College London, who was not involved in the study. “The reason some people may not have seen these specialized functions is they were studying different astrocytes.” © 2023 SCIENTIFIC AMERICAN,

Keyword: Glia
Link ID: 29025 - Posted: 11.26.2023

By Erin Garcia de Jesús A new brain-monitoring device aims to be the Goldilocks of anesthesia delivery, dispensing drugs in just the right dose. No physician wants a patient to wake up during surgery — nor do patients. So anesthesiologists often give more drug than necessary to keep patients sedated during medical procedures or while on lifesaving machines like ventilators. But anesthetics can sometimes be harmful when given in excess, says David Mintz, an anesthesiologist at Johns Hopkins University. For instance, elderly people with cognitive conditions like dementia or age-related cognitive decline may be at higher risk of post-surgical confusion. Studies also hint that long periods of use in young children might cause behavioral problems. “The less we give of them, the better,” Mintz says. An automated anesthesia delivery system could help doctors find the right drug dose. The new device monitored rhesus macaques’ brain activity and supplied a common anesthetic called propofol in doses that were automatically adjusted every 20 seconds. Fluctuating doses ensured the animals received just enough drug — not too much or too little — to stay sedated for 125 minutes, researchers reported October 31 in PNAS Nexus. The study is a step toward devising and testing a system that would work for people. © Society for Science & the Public 2000–2023.

Keyword: Consciousness; Pain & Touch
Link ID: 29021 - Posted: 11.26.2023

By Laura Dattaro A brain is nothing if not communicative. Neurons are the chatterboxes of this conversational organ, and they speak with one another by exchanging pulses of electricity using chemical messengers called neurotransmitters. By repeating this process billions of times per second, a brain converts clusters of chemicals into coordinated actions, memories and thoughts. Researchers study how the brain works by eavesdropping on that chemical conversation. But neurons talk so loudly and often that if there are other, quieter voices, it might be hard to hear them. For most of the 20th century, neuroscientists largely agreed that neurons are the only brain cells that propagate electrical signals. All the other brain cells, called glia, were thought to serve purely supportive roles. Then, in 1990, a curious phenomenon emerged: Researchers observed an astrocyte, a subtype of glial cell, responding to glutamate, the main neurotransmitter that generates electrical activity. In the decades since, research teams have come up with conflicting evidence, some reporting that astrocytes signal, and others retorting that they definitely do not. The disagreement played out at conferences and in review after review of the evidence. The two sides seemed irreconcilable. A new paper published in Nature in September presents the best proof yet that astrocytes can signal, gathered over eight years by a team co-led by Andrea Volterra, visiting faculty at the Wyss Center for Bio and Neuro Engineering in Geneva, Switzerland. The study includes two key pieces of evidence: images of glutamate flowing from astrocytes, and genetic data suggesting that these cells, dubbed glutamatergic astrocytes, have the cellular machinery to use glutamate the way neurons do. The paper also helps explain the decades of contradictory findings. Because only some astrocytes can perform this signaling, both sides of the controversy are, in a sense, right: A researcher’s results depend on which astrocytes they sampled. All Rights Reserved © 2023

Keyword: Glia
Link ID: 28972 - Posted: 10.25.2023

by Angie Voyles Askham About once a month throughout 2012, researchers from four labs at the University of California, San Francisco filed into a conference room in the early morning to hear the latest news on their ambitious project. The heads of the labs — Arturo Alvarez-Buylla, Scott Baraban, Arnold Kriegstein and John Rubenstein — had formed the company Neurona Therapeutics in 2008 to develop a new approach to treating neurological conditions, using cell therapy. Their goal was to transplant inhibitory interneurons into people’s nervous systems to treat the overexcited circuits that can give rise to conditions such as epilepsy, Alzheimer’s disease and neuropathic pain. These meetings had grown tense as researchers within the four groups struggled to see eye to eye on data interpretation, particularly when Cory Nicholas, then a postdoctoral researcher in Kriegstein’s lab, presented his protocol for producing the inhibitory interneurons. On those days, Nicholas would open his slide deck to reveal images of fluorescent cells on a large screen behind him — red and white branching blobs against a black background. Then the questions would come from Baraban’s group. Why do some of the cells seem to be the wrong kind? Are they forming tumors? Can we see the neighboring images? There were some in the audience who thought they were being shown only the best images, says Joy Sebe, a postdoc in Baraban’s lab at the time. Nicholas, for his part, says he welcomed the questioning — in science, he says, “your job is to challenge” — and Daniel Vogt, who was a postdoc Rubenstein’s lab at the time, says the back and forth was simply part of the scientific process. © 2023 Simons Foundation

Keyword: Epilepsy
Link ID: 28948 - Posted: 10.07.2023

Max Kozlov Doctors measure blood pressure to track heart disease, and scrutinize insulin levels in people with diabetes. But when it comes to depression, clinicians must rely on people’s self-reported symptoms, making it difficult to objectively measure a treatment’s effects. Now, researchers have used artificial intelligence (AI) to identify a brain signal linked to recovery from depression in people treated with deep-brain stimulation (DBS), a technique that uses electrodes implanted into the brain to deliver electric pulses that alter neural activity. The team reported1 its results on ten people with severe depression, in Nature on 20 September. If replicated in a larger sample, these findings could represent a “game-changer in how we would be able to treat depression”, says Paul Holtzheimer, a neuroscientist at the Geisel School of Medicine at Dartmouth in Hanover, New Hampshire, who was not involved in the research. Efforts to treat depression with DBS have so far had limited success: two randomized-controlled trials2,3 failed to demonstrate a benefit compared with a placebo. One problem, says Helen Mayberg, a neurologist at Icahn School of Medicine at Mount Sinai in New York City, and a co-author of the Nature paper, is that doctors only have access to self-reported data to assess whether a person’s stimulation voltage needs adjustment. With self-reported data, clinicians have a difficult time distinguishing between normal, day-to-day mood fluctuations and pathological depression, says Todd Herrington, director of the DBS programme at Massachusetts General Hospital in Boston, who was not involved in the research. To find a more objective measure of depression recovery, Mayberg and her colleagues developed a DBS device that includes sensors to measure brain activity, as well as the standard electrodes for brain stimulation. They implanted this device into the subcallosal cingulate cortex — an area of the brain that has a role in regulating emotional behaviour — in ten people with depression that resisted all forms of treatment. © 2023 Springer Nature Limited

Keyword: Depression; Brain imaging
Link ID: 28932 - Posted: 09.27.2023

by Maris Fessenden A new lightweight device with a wisplike tether can record neural activity while mice jump, run and explore their environment. The open-source recording system, which its creators call ONIX, overcomes several of the limitations of previous systems and enables the rodents to move more freely during recording. The behavior that ONIX allows brings to mind children running around in a playground, says Jakob Voigts, a researcher at the Howard Hughes Medical Institute’s Janelia Research Campus in Ashburn, Virginia, who helped build and test the system. He and his colleagues describe their work in a preprint posted on bioRxiv earlier this month. To understand how the brain creates complex behaviors — such as those found in social interaction, sensory processing and cognition, which are commonly affected in autism — researchers observe brain signals as these behaviors unfold. Head-mounted devices enable researchers to eavesdrop on the electrical chatter between brain cells in mice, rats and primates. But as the smallest of these animal models, mice present some significant challenges. Current neural recording systems are bulky and heavy, making the animals carry up to a fifth of their body weight on their skulls. Predictably, this slows the mice down and tires them out. And most neural recording systems use a tether to relay signals from the mouse’s brain to a computer. But this tether twists and tangles as the mouse turns its head and body, exerting torque that the mouse can feel. Researchers must therefore periodically replace or untangle the tether. Longer tethers allow for more time to elapse between changeouts, but the interruptions still affect natural behavior. And battery-powered, wireless systems add too much weight. Altogether, these challenges inhibit natural behaviors and limit the amount of time that recording can take place, preventing scientists from studying, for example, the complete process of learning a new task. © 2023 Simons Foundation

Keyword: Brain imaging
Link ID: 28930 - Posted: 09.27.2023

By Laura Sanders On a hot, sunny Sunday afternoon in Manhattan, time froze for Jon Nelson. He stood on the sidewalk and said good-bye to his three kids, whose grandfather had come into the city from Long Island to pick them up. Like any parent, Jon is deeply attuned to his children’s quirks. His oldest? Sometimes quiet but bitingly funny. His middle kid? Rates dad a 10 out of 10 on the embarrassment scale and doesn’t need a hug. His 10-year-old son, the baby of the family, is the emotional one. “My youngest son would climb back up into my wife’s womb if he could,” Jon says. “He’s that kid.” An unexpected parade had snarled traffic, so Jon parked illegally along a yellow curb on 36th Street, near where his father-in-law was waiting. It was time to go. His youngest gave the last hug. “He looked up, scared and sad,” Jon says, and asked, “Dad, am I going to see you again?” That question stopped the clock. “I was like, ‘Oh man,’” Jon says. “It was one of those moments where I was living it through his eyes. And I got scared for the first time.” Until that good-bye, Jon hadn’t wanted to live. For years, he had a constant yearning to die — he talks about it like it was an addiction — as he fought deep, debilitating depression. But his son’s question pierced through that heaviness and reached something inside him. “That was the first time I really thought about it. I was like, ‘I kind of hope I don’t die.’ I hadn’t had that feeling in so long.” That hug happened around 5 p.m. on August 21, 2022. Twelve hours later, Jon was wheeled into a surgical suite. There, at Mount Sinai’s hospital just southwest of Central Park, surgery team members screwed Jon’s head into a frame to hold it still. Then they numbed him and drilled two small holes through the top of his skull, one on each side. Through each hole, a surgeon plunged a long, thin wire dotted at the end with electrodes deep into his brain. The wiring, threaded under his skin, snaked around the outside of Jon’s skull and sank down behind his ear. From there, a wire wrapped around to the front, meeting a battery-powered control box that surgeons implanted in his chest, just below his collarbone. © Society for Science & the Public 2000–2023.

Keyword: Depression
Link ID: 28924 - Posted: 09.23.2023