Not unique to humans but uniquely human: researchers identify factor involved in brain expansion in humans

A microscopy image of a human brain organoid.
Image Credit: © Janine Hoffmann

What makes us human? According to neurobiologists it is our neocortex. This outer layer of the brain is rich in neurons and lets us do abstract thinking, create art, and speak complex languages. An international team led by Dr. Mareike Albert at the Center for Regenerative Therapies Dresden (CRTD) of TUD Dresden University of Technology has identified a new factor that might have contributed to neocortex expansion in humans. The results were published in the EMBO Journal.

The neocortex is the characteristic folded outer layer of the brain that resembles a walnut. It is responsible for higher cognitive functions such as abstract thinking, art, and language. “The neocortex is the most recently evolved part of the brain,” says Dr. Mareike Albert, research group leader at the CRTD. “All mammals have a neocortex, but it varies in size and complexity. Human and primate neocortices have folds while, for example, mice have a completely smooth neocortex, without any creases.”

The folds characteristic of the human brain increases the surface area of the neocortex. The human neocortex has a greater number of neurons that support complex cognitive functions.

The molecular mechanisms driving neocortex evolution are still largely unknown. “Which genes are responsible for inter-species differences in neocortex size? What factors have contributed to brain expansion in humans? Answering these questions is crucial to understanding human brain development and potentially addressing mental health disorders,” explains Dr. Albert.

Seeing a Path to Nerve Regeneration

The image on the left (A) shows four optic nerves that have been crushed. Live nerve tissue glows green in this image, while damaged nerve tissue is dark. The top nerve was not treated with any regenerative factors, and there is no regrowth of the nerve (shown by the uniformly dark area on the right.) The second and third nerves were treated with previously identified regeneration factors, and show some live nerve tissue beyond the crushed area. The bottom nerve was treated with Nfe3, and also shows live nerve tissue beyond the crushed region. (B) shows close-ups of the left, middle, and far right sections of the crushed nerves. The nerve treated with Nfe3 (bottom) shows regeneration as good or better than the nerves treated with the other factors (middle two rows).
Image Credit: Courtesy of researcher Et al Experimental Neurology and University of Connecticut

This opens a whole new novel realm of research. It could help glaucoma and other types of nerve damage

Damage to the optic nerve can lead to irreversible blindness. A newly investigated regeneration factor could change that, UConn researchers report in the May 2024 issue of Experimental Neurology.

Blindness and vision impairment due to optic nerve damage affect more than 3 million people in the US alone, according to the Centers for Disease Control (CDC). The most common reason for that damage is glaucoma, a family of eye diseases that affect the flow of liquid in the eye, eventually damaging the long bundle of cells that connect the retina to the brain. That bundle of cells is the optic nerve. They don’t grow back after being damaged, leading to permanent vision loss.

Now, a team of researchers in the lab of UConn School of Medicine neuroscientist Ephraim Trakhtenberg have shown that a protein previously thought unimportant can stimulate regrowth of nerve cells. The protein is called nuclear factor erythroid 3 (Nfe3), and it is unique to nerves originating in the retina. Normally it is not produced by adult neurons.

Human brains are getting larger. That may be good news for dementia risk

Image Credit: Dmitriy Gutarev

A new study by researchers at UC Davis Health found human brains are getting larger. Study participants born in the 1970s had 6.6% larger brain volumes and almost 15% larger brain surface area than those born in the 1930s.

The researchers hypothesize the increased brain size may lead to an increased brain reserve, potentially reducing the overall risk of age-related dementias.

The findings were published in JAMA Neurology.

“The decade someone is born appears to impact brain size and potentially long-term brain health,” said Charles DeCarli, first author of the study. DeCarli is a distinguished professor of neurology and director of the UC Davis Alzheimer’s Disease Research Center. “Genetics plays a major role in determining brain size, but our findings indicate external influences — such as health, social, cultural and educational factors — may also play a role.”

The aging brain: protein mapping furnishes new insights

Stained mouse microvessels under the fluorescence microscope (green: vascular endothelium, red: cell nuclei). 
Image Credit: © Dichgans Lab

For the neurons in the brain to work smoothly and be able to process information, the central nervous system needs a strictly regulated environment. This is maintained by the blood-brain barrier, whereby specialized brain endothelial cells lining the inner walls of blood vessels regulate the exchange of molecules between the circulatory and nervous systems. Earlier studies have shown that various functions that are dependent on these cells, such as the integrity of the blood-brain barrier or the regulation of blood supply to the brain, decline over the course of a person’s life. This dysregulation leads to a dysfunction of the brain vasculature and is therefore a major contributor to medical conditions such as strokes and dementia.

However, the molecular changes that underlie this loss of function have remained largely obscure. To improve our mechanistic understanding, researchers carry out molecular profiling studies to investigate the different components of brain endothelial cells and collect their findings in large databases. “The transcriptome – that is to say, the RNA contained in endothelial cells – has since been quite comprehensively mapped,” says LMU professor Martin Dichgans, Director of the Institute for Stroke and Dementia Research at University of Munich Hospital and Principal Investigator at the SyNergy Cluster of Excellence. “What has been lacking is corresponding data on the complete set of proteins in the cells, the proteome.” A study recently published in the journal Nature Aging, which had major contributions by researchers from LMU and SyNergy, has now closed this knowledge gap.

Research offers hope for preventing post-COVID ‘brain fog’ by targeting brain’s blood vessels

Blood vessel endothelial cells (green) and basement membrane (red) in the brain.
Image Credit: Sarah Lutz

Among the many confounding symptoms in patients recovering from a COVID-19 infection are memory loss and difficulty learning. Yet little is known about the mechanisms of cognitive impairments like these, commonly called brain fog. 

In a new study, researchers at the University of Illinois Chicago have identified a mechanism that causes neurological problems in mice infected with SARS-CoV-2, the virus behind COVID-19. The researchers also found a treatment that helped prevent these changes. Sarah Lutz, assistant professor of anatomy and cell biology in the College of Medicine, led the research, which was published in the journal Brain.

The team focused on the blood-brain barrier, which plays a role in other neurological diseases, such as multiple sclerosis. Normally, this barrier protects the brain from potentially harmful cells or molecules circulating in the bloodstream. But the infected mice, researchers found, had leaky blood-brain barrier vessels and impaired memory or learning.

To understand why, the researchers looked at blood vessels from the brains of infected mice to see which genes were most altered. They found a significant decrease in a signaling pathway called Wnt/beta-catenin, which helps maintain the health of the blood-brain barrier and protects the brain from damage.

Neighboring synapses shape learning and memory

A mathematical model reveals how interactions between neighboring contact sites of nerve cells influence learning.
Image Credit: University of Basel, Biozentrum

A researcher at the University of Basel, in collaboration with a colleague in Austria, has developed a new model that provides a holistic view on how our brain manages to learn quickly and forms stable, long-lasting memories. Their study sheds light on the crucial role of interactions among neighboring contact sites of nerve cells for brain plasticity – the brain’s ability to adapt to new experiences.

In 1949, the Canadian psychologist Donald O. Hebb described that connections between neurons become stronger when the neurons are active at the same time and that strengthened connections facilitate signal transmission. The ability of our brain to modify the connections between neurons is fundamental for learning and memory.

 “It has long been assumed that these adaptations occur mostly on a one-on-one basis at specific synapses, the contact sites between two neurons”, explains Dr. Everton Agnes from the Biozentrum, University of Basel. “Interestingly, synapses that undergo changes also affect multiple neighboring synapses.” As these complex synaptic interactions are difficult to investigate experimentally, Agnes and his colleague Prof. Tim Vogels from the Institute of Science and Technology Austria have built a theoretical model to disentangle this phenomenon, also known as co-dependency. Their work has recently been published in Nature Neuroscience.

Craving snacks after a meal? It might be food-seeking neurons, not an overactive appetite

The discovery of a circuit in the brain of mice that makes them seek fatty food, even when they are not hungry, could have implications for future understanding of and treatment for human eating disorders.
Photo Credit: Annie Spratt

People who find themselves rummaging around in the refrigerator for a snack not long after they’ve eaten a filling meal might have overactive food-seeking neurons, not an overactive appetite.

UCLA psychologists have discovered a circuit in the brain of mice that makes them crave food and seek it out, even when they are not hungry. When stimulated, this cluster of cells propels mice to forage vigorously and to prefer fatty and pleasurable foods like chocolate over healthier foods like carrots.

People possess the same kinds of cells, and if confirmed in humans, the finding could offer new ways of understanding eating disorders.

The report, published in the journal Nature Communications, is the first to find cells dedicated to food-seeking in a part of the mouse brainstem usually associated with panic, but not with feeding.

“This region we’re studying is called the periaqueductal gray (PAG), and it is in the brainstem, which is very old in evolutionary history and because of that, it is functionally similar between humans and mice,” said corresponding author Avishek Adhikari, a UCLA associate professor of psychology. “Although our findings were a surprise, it makes sense that food-seeking would be rooted in such an ancient part of the brain, since foraging is something all animals need to do.”

Two artificial intelligences talk to each other

A UNIGE team has developed an AI capable of learning a task solely on the basis of verbal instructions. And to do the same with a «sister» AI.
Prompts by Scientific Frontline
Image Credit: AI Generated by Copilot / Designer / DALL-E

Performing a new task based solely on verbal or written instructions, and then describing it to others so that they can reproduce it, is a cornerstone of human communication that still resists artificial intelligence (AI). A team from the University of Geneva (UNIGE) has succeeded in modelling an artificial neural network capable of this cognitive prowess. After learning and performing a series of basic tasks, this AI was able to provide a linguistic description of them to a ‘‘sister’’ AI, which in turn performed them. These promising results, especially for robotics, are published in Nature Neuroscience.

Performing a new task without prior training, on the sole basis of verbal or written instructions, is a unique human ability. What’s more, once we have learned the task, we are able to describe it so that another person can reproduce it. This dual capacity distinguishes us from other species which, to learn a new task, need numerous trials accompanied by positive or negative reinforcement signals, without being able to communicate it to their congeners.

A sub-field of artificial intelligence (AI) - Natural language processing - seeks to recreate this human faculty, with machines that understand and respond to vocal or textual data. This technique is based on artificial neural networks, inspired by our biological neurons and by the way they transmit electrical signals to each other in the brain. However, the neural calculations that would make it possible to achieve the cognitive feat described above are still poorly understood.

The integrity of the blood-brain barrier depends on a protein that is altered in some neurodegenerative diseases

From left to right, Pilar Villacampa, Víctor Arribas and Eloi Montañez.
Photo Credit: Courtesy of University of Barcelona

Defects in the blood vessel network of the central nervous system have been linked to early symptoms of neurodegenerative diseases such as Alzheimer's disease and amyotrophic lateral sclerosis (ALS). It is this complex vascular network that provides the necessary nutrients, especially glucose and oxygen to activate all neuronal functions. Now, a study led by the University of Barcelona and the Bellvitge Biomedical Research Institute (IBIDELL) reveals that the TDP-43 protein is essential for forming a stable and mature blood vessel network in the central nervous system.

According to the study the TDP-43 protein is also critical in maintaining the integrity of the blood-brain barrier, which prevents toxins and pathogens from reaching the central nervous system.

The project is led by Professor Eloi Montañez, from the Faculty of Medicine and Health Sciences of the University of Barcelona and IDIBELL, and involves teams from the Faculty of Biology and the Institute of Biomedicine of the UB (IBUB), the Josep Carreras Leukemia Research Institute, and the National Centre for Genomic Analysis (CNAG-CRG).

Brain Waves Travel in One Direction When Memories Are Made and the Opposite When Recalled

Traveling wave propagation directions in the memory task reveal how the brain quickly coordinates activity and shares information across multiple regions.
Photo Credit: Hongui Zhang

In the space of just a few seconds, a person walking down a city block might check their phone, yawn, worry about making rent, and adjust their path to avoid a puddle. The smell from a food cart could suddenly conjure a memory from childhood, or they could notice a rat eating a slice of pizza and store the image as a new memory. 

For most people, shifting through behaviors quickly and seamlessly is a mundane part of everyday life. 

For neuroscientists, it’s one of the brain’s most remarkable capabilities. That’s because different activities require the brain to use different combinations of its many regions and billions of neurons. How it manages to do this so rapidly has been an open question for decades. 

The study

In a paper published in Nature Human Behaviour, a team of researchers, led by Joshua Jacobs, associate professor of biomedical engineering at Columbia Engineering, shed new light on this question. By carefully monitoring neural activity of people who were recalling memories or forming new ones, the researchers managed to detect how a newly appreciated type of brainwave — traveling waves — influences the storage and retrieval of memories. 

“Broadly, we found that waves tended to move from the back of the brain to the front while patients were putting something into their memory,” said the paper’s co-author Uma R. Mohan, a postdoctoral researcher at NIH and former postdoctoral researcher in the Electrophysiology, Memory, and Navigation Laboratory at Columbia Engineering. “When patients were later searching to recall the same information, those waves moved in the opposite direction, from the front towards the back of the brain,” she said. 

Researchers uncover protein responsible for cold sensation

Image Credit: Copilot AI Generated 

University of Michigan researchers have identified the protein that enables mammals to sense cold, filling a long-standing knowledge gap in the field of sensory biology.

The findings, published in Nature Neuroscience, could help unravel how we sense and suffer from cold temperatures in the winter, and why some patients experience cold differently under particular disease conditions.

“The field started uncovering these temperature sensors over 20 years ago, with the discovery of a heat-sensing protein called TRPV1,” said neuroscientist Shawn Xu, a professor at the U-M Life Sciences Institute and a senior author of the new research.

“Various studies have found the proteins that sense hot, warm, even cool temperatures—but we’ve been unable to confirm what senses temperatures below about 60 degrees Fahrenheit.”

In a 2019 study, researchers in Xu’s lab discovered the first cold-sensing receptor protein in Caenorhabditis elegans, a species of millimeter-long worm that the lab studies as a model system for understanding sensory responses.

What Makes Birds So Smart?

The avian brain is smaller than that of many mammals, but just as capable.
Photo Credit: Kevin Mueller

Researchers at Ruhr University Bochum explain how it is possible for the small brains of pigeons, parrots and corvids to perform equally well as those of mammals, despite their significant differences.

Since the late 19th century, it has been a common belief among researchers that high intelligence requires the high computing capacity of large brains. They also discovered that the cerebral cortex as typical of mammals, is necessary to analyze and link information in great detail. Avian brains, by contrast, are very small and lack any structure resembling a cortex. Nevertheless, scientists showed that parrots and corvids are capable of planning for the future, forging social strategies, recognizing themselves in the mirror and building tools. These and similar aptitudes put them on a par with chimpanzees. Even less gifted birds, such as pigeons, learn orthographic rules that enable them to recognize typos in short words or classify pictures according to categories such as “impressionism”, “water” or “man-made”. How do they do it with such small brains and without a cortex? With their article in Trends in Cognitive Science, Professor Onur Güntürkün, Dr. Roland Pusch and Professor Jonas Rose from Ruhr University Bochum come closer to solving this more than one hundred-year-old puzzle.

How the Body Copes With Airway Closure

Image Credit: Scientific Frontline stock image

There is perhaps no bodily function more essential for humans and other mammals than breathing. With each breath, we suffuse our bodies with oxygen-rich air that keeps our organs and tissues healthy and working properly — and without oxygen, we can survive mere minutes.

But sometimes, our breathing becomes restricted, whether due to infection, allergies, exercise, or some other cause, forcing us to take deep, gasping breaths to quickly draw in more air.

Now, researchers at Harvard Medical School have identified a previously unknown way in which the body counteracts restricted breathing — a new reflex of the vagus nerve that initiates deep breathing. Their work is published in Nature.

The research, conducted in mice, reveals a rare and mysterious cell type in the lungs that detects airway closure and relays the signal to the vagus nerve — the information highway that connects the brain to almost every major organ. After the signal reaches the brain, a gasping reflex is initiated that helps the animal compensate for the lack of air.

Earliest-yet Alzheimer’s biomarker found in mouse model could point to new targets

Illinois graduate student Yeeun Yook, left, and professor Nien-Pei Tsai worked with their team to find the earliest marker of Alzheimer’s disease yet reported in the brains of mice. The work could create new targets for early detection or treatment options.
Photo Credit: Fred Zwicky

A surge of a neural-specific protein in the brain is the earliest-yet biomarker for Alzheimer’s disease, report University of Illinois Urbana-Champaign researchers studying a mouse model of the disease. Furthermore, the increased protein activity leads to seizures associated with the earliest stages of neurodegeneration, and inhibiting the protein in the mice slowed the onset and progression of seizure activity. 

The neural-specific protein, PSD-95, could pose a new target for Alzheimer’s research, early diagnosis and treatment, said study leader Nien-Pei Tsai, an Illinois professor of molecular and integrative physiology. 

Tsai’s group studies mice that make more of the proteins that form amyloid-beta, which progressively aggregates in Alzheimer’s disease to form plaques in the brain that hamper neural activity. However, in the new work, the group focused on a time frame much earlier in the mouse lifespan than others have studied – when no other markers or abnormalities have been reported, Tsai said.

Dopamine production is not behind vulnerability to cocaine abuse

Averaged parametric brain maps of [18F]-FDOPA kicer, and index of dopamine synthesis capacity, in high- and low-impulsive rats before and after repeated cocaine self-administration.
Image Credit: © 2024 Urueña-Méndez et al.

Why do some people who try drugs struggle with substance abuse while others don’t? This question has long puzzled scientists. A team from the University of Geneva (UNIGE) explored the complex interplay between personality traits and brain chemistry. The scientists studied the role of impulsivity and the production of dopamine – the so-called "happiness hormone" – in influencing the risk of cocaine abuse. These results, published in eNeuro, offer new keys to understanding vulnerability to drug abuse, which could lead to the development of more targeted interventions for people at risk.

When a person consumes an addictive drug, his or her dopamine release surges, creating a “high” feeling. With repeated drug use, this dopamine release drops, potentially driving the person to increase drug consumption. This mechanism varies between individuals, with some showing a greater propensity to consume the drug while others don’t. However, the reasons for these differences are unknown.

Neurons help flush waste out of brain during sleep

Researchers at Washington University School of Medicine in St. Louis have found that brain cell activity during sleep is responsible for propelling fluid into, through and out of the brain, cleaning it of debris.
Image Credit: Scientific Frontline stock image.

There lies a paradox in sleep. Its apparent tranquility juxtaposes with the brain’s bustling activity. The night is still, but the brain is far from dormant. During sleep, brain cells produce bursts of electrical pulses that cumulate into rhythmic waves — a sign of heightened brain cell function.

But why is the brain active when we are resting?

Slow brain waves are associated with restful, refreshing sleep. And now, scientists at Washington University School of Medicine in St. Louis has found that brain waves help flush waste out of the brain during sleep. Individual nerve cells coordinate to produce rhythmic waves that propel fluid through dense brain tissue, washing the tissue in the process.

“These neurons are miniature pumps. Synchronized neural activity powers fluid flow and removal of debris from the brain,” explained first author Li-Feng Jiang-Xie, a postdoctoral research associate in the Department of Pathology & Immunology. “If we can build on this process, there is the possibility of delaying or even preventing neurological diseases, including Alzheimer’s and Parkinson’s disease, in which excess waste — such as metabolic waste and junk proteins — accumulate in the brain and lead to neurodegeneration.”

Gut-brain communication turned on its axis

How the gut communicates with the brain
Image Credit: Copilot AI

The mechanisms by which antidepressants and other emotion-focused medications work could be reconsidered due to an important new breakthrough in the understanding of how the gut communicates with the brain.

New research led by Flinders University has uncovered major developments in understanding how the gut communicates with the brain, which could have a profound impact on the make-up and use of medications such as antidepressants.

“The gut-brain axis consists of complex bidirectional neural communication pathway between the brain and the gut, which links emotional and cognitive centers of the brain,” says Professor Nick Spencer from the College of Medicine and Public Health.

“As part of the gut-brain axis, vagal sensory nerves relay a variety of signals from the gut to the brain that play an important role in mental health and wellbeing.

“The mechanisms by which vagal sensory nerve endings in the gut wall are activated has been a major mystery but remains of great interest to medical science and potential treatments for mental health and wellbeing.”

Human stem cells coaxed to mimic the very early central nervous system

Jianping Fu, Ph.D., Professor of Mechanical Engineering at the University of Michigan and the corresponding author of the paper being published at Nature discusses his team’s work in their lab with Jeyoon Bok, Ph.D. candidate at the Department of Mechanical Engineering.
Photo Credit: Marcin Szczepanski, Michigan Engineering

The first stem cell culture method that produces a full model of the early stages of the human central nervous system has been developed by a team of engineers and biologists at the University of Michigan, the Weizmann Institute of Science, and the University of Pennsylvania.

“Models like this will open doors for fundamental research to understand early development of the human central nervous system and how it could go wrong in different disorders,” said Jianping Fu, U-M professor of mechanical engineering and corresponding author of the study in Nature.

The system is an example of a 3D human organoid—stem cell cultures that reflect key structural and functional properties of human organ systems but are partial or otherwise imperfect copies.

“We try to understand not only the basic biology of human brain development, but also diseases—why we have brain-related diseases, their pathology, and how we can come up with effective strategies to treat them,” said Guo-Li Ming, who along with Hongjun Song, both Perelman Professors of Neuroscience at UPenn and co-authors of the study, developed protocols for growing and guiding the cells and characterized the structural and cellular characteristics of the model.

Study sheds light on how neurotransmitter receptors transport calcium, a process linked with origins of neurological disease

Illustration Credit: Courtesy of McGill University

A new study from a team of McGill University and Vanderbilt University researchers is shedding light on our understanding of the molecular origins of some forms of autism and intellectual disability.

For the first time, researchers were able to successfully capture atomic resolution images of the fast-moving ionotropic glutamate receptor (iGluR) as it transports calcium. iGluRs and their ability to transport calcium are vitally important for many brain functions such as vision or other information coming from sensory organs. Calcium also brings about changes in the signaling capacity of iGluRs and nerve connections which are a key cellular events that lead to our ability to learn new skills and form memories.

iGluRs are also key players in brain development and their dysfunction through genetic mutations has been shown to give rise to some forms of autism and intellectual disability. However, basic questions about how iGluRs trigger biochemical changes in the brain’s physiology by transporting calcium have remained poorly understood.

In the study, the researchers took millions of snapshots of the iGluR protein in the act of transporting calcium, and unexpectedly discovered a temporary pocket that traps calcium on the outside of the protein. With this information at hand, they then used high-resolution electrophysiological recordings to watch the protein in motion as it transported calcium into the nerve cell.

Arterial Connections Improve Treatment Outcomes Following Stroke

Visualization of the blood vessels in the brain of a patient without early venous filling, meaning without excessive reperfusion of the brain area after removal of the blood clot in the blocked artery.
Image Credit: P. Thurner und Z. Kulcsar, USZ

Blood vessels that cross-connect adjacent arterial trees regulate blood flow to the brain in stroke patients. Researchers at the University of Zurich have now shown that these vessels prevent brain hemorrhage following treatment to remove blood clots. They play a crucial role in the recovery of stroke patients.

Ischemic strokes are a major health burden. They occur when a blood vessel that supplies the brain becomes blocked, impairing blood flow to the brain. As a result, brain tissue suffers from a lack of oxygen and nutrients, which causes symptoms such as paralysis, confusion, dizziness, headache, trouble speaking or even death.

Many stroke patients recover poorly despite timely treatment

To treat these symptoms and restore blood flow to the brain, the obstructed vessel needs to be “declogged”, or recanalized. Contemporary treatments to remove the clot include intravenous thrombolysis or mechanical thrombectomy using a catheter. However, even with timely clot removal, many stroke patients only recover poorly.

The research group of Susanne Wegener, professor at the University of Zurich (UZH) and senior leading physician at the Department of Neurology of the University Hospital Zurich (USZ), has now demonstrated that the outcome of stroke treatments depends on the collateral network. Collaterals are blood vessels that cross-connect adjacent arterial trees, providing potential detour networks in case of a vascular blockage. “These vascular bridges maintain cerebral autoregulation and allow for a slower, gradual reperfusion, which results in smaller infarcts,” says Wegener.