How Electric Fish Were Able to Evolve Electric Organs

UT Austin researchers confirmed that the genetic control region they discovered only controls the expression of a sodium channel gene in muscle and no other tissues. In this image, a green fluorescent protein lights up only in trunk muscle in a developing zebrafish embryo.
Image credit: Mary Swartz/Johann Eberhart/University of Texas at Austin.

Electric organs help electric fish, such as the electric eel, do all sorts of amazing things: They send and receive signals that are akin to bird songs, helping them to recognize other electric fish by species, sex and even individual. A new study in Science Advances explains how small genetic changes enabled electric fish to evolve electric organs. The finding might also help scientists pinpoint the genetic mutations behind some human diseases.

Evolution took advantage of a quirk of fish genetics to develop electric organs. All fish have duplicate versions of the same gene that produces tiny muscle motors, called sodium channels. To evolve electric organs, electric fish turned off one duplicate of the sodium channel gene in muscles and turned it on in other cells. The tiny motors that typically make muscles contract were repurposed to generate electric signals, and voila! A new organ with some astonishing capabilities was born.

“This is exciting because we can see how a small change in the gene can completely change where it’s expressed,” said Harold Zakon, professor of neuroscience and integrative biology at The University of Texas at Austin and corresponding author of the study.

In the new paper, researchers from UT Austin and Michigan State University describe discovering a short section of this sodium channel gene—about 20 letters long—that controls whether the gene is expressed in any given cell. They confirmed that in electric fish, this control region is either altered or entirely missing. And that’s why one of the two sodium channel genes is turned off in the muscles of electric fish. But the implications go far beyond the evolution of electric fish.

Alzheimer’s disease causes cells to overheat and ‘fry like eggs’

Mammalian cell stained with fluorescence polymeric thermometers and falsely-colored based on temperature gradients. 
Credit: Chyi Wei Chung

The researchers, from the University of Cambridge, used sensors small and sensitive enough to detect temperature changes inside individual cells, and found that as amyloid-beta misfolds and clumps together, it causes cells to overheat.

In an experiment using human cell lines, the researchers found the heat released by amyloid-beta aggregation could potentially cause other, healthy amyloid-beta to aggregate, causing more and more aggregates to form.

In the same series of experiments, the researchers also showed that amyloid-beta aggregation can be stopped, and the cell temperature lowered, with the addition of a drug compound. The experiments also suggest that the compound has potential as a therapeutic for Alzheimer’s disease, although extensive tests and clinical trials would first be required.

The researchers say their assay could be used as a diagnostic tool for Alzheimer’s disease, or to screen potential drug candidates. The results are reported in the Journal of the American Chemical Society.

Chemists reveal how tau proteins form tangles

MIT chemists have used nuclear magnetic resonance (NMR) spectroscopy to reveal how two different forms of the Tau protein mix to form the tangles seen in the brains of Alzheimer’s patients. 
Credit: Aurelio Dregni/Nadia El-Mammeri/Hong Lab at MIT

One of the hallmarks of Alzheimer’s disease is the presence of neurofibrillary tangles in the brain. These tangles, made of tau proteins, impair neurons’ ability to function normally and can cause the cells to die.

A new study from MIT chemists has revealed how two types of tau proteins, known as 3R and 4R tau, mix together to form these tangles. The researchers found that the tangles can recruit any tau protein in the brain, in a nearly random way. This feature may contribute to the prevalence of Alzheimer’s disease, the researchers say.

“Whether the end of an existing filament is a 3R or 4R tau protein, the filament can recruit whichever tau version is in the environment to add onto the growing filament. It is very advantageous for the Alzheimer’s disease tau structure to have that property of randomly incorporating either version of the protein,” says Mei Hong, an MIT professor of chemistry.

Hong is the senior author of the study, which appears today in Nature Communications. MIT graduate student Aurelio Dregni and postdoc Pu Duan are the lead authors of the paper.

New sensors allow the exact measurement of the messenger substance dopamine

Sebastian Kruss (right) and Björn Hill belong to the team that was able to measure the messenger substance dopamine directly.
Credit: RUB, Kramer

Carbon nanotubes shine brighter in the presence of the messenger. In this way, signals between nerve cells can be measured easily and precisely.

Dopamine is an important signaling molecule for nerve cells. So far, its concentration could not be determined spatially and temporally. Thanks to a new process, this is now possible: A research team from Bochum, Göttingen and Duisburg used modified carbon nanotubes that glow brighter in the presence of the messenger substance dopamine. With these sensors, the release of dopamine from nerve cells with a resolution that has not yet been achieved has been made visible. The researchers around Prof. Dr. Sebastian Kruss from the Physical Chemistry of the Ruhr University Bochum (RUB) and Dr. James Daniel and Prof. Dr. Nils Brose from the Max Planck Institute for Multidisciplinary Natural Sciences in Göttingen reports on this in the journal PNAS.

Fluorescence changes in the presence of dopamine

The messenger substance dopamine controls, among other things, the reward center of the brain. If this signal transmission no longer works, diseases such as Parkinson's can occur. In addition, the chemical signals are changed by drugs such as cocaine and play a role in addiction. "However, there was previously no method with which the dopamine signals could be made visible at the same time with high spatial and temporal resolution," explains Sebastian Kruss, head of the functional interfaces and biosystems group at the RUB and member of the Ruhr Explores Solvation Cluster of Excellence, in short RESOLV, and the Research Training Group International Graduate School of Neuroscience (IGSN).

Bat Brains Organized for Echolocation and Flight

Researchers at the UC Davis Center for Neuroscience mapped the brain regions controlling movements in Egyptian fruit bats. Large regions of motor cortex are dedicated to the tongue, which makes sonar sounds, and coordinated movements of fore- and hindlimbs for flying

A new study shows how the brains of Egyptian fruit bats are highly specialized for echolocation and flight, with motor areas of the cerebral cortex that are dedicated to sonar production and wing control. The work by researchers at the University of California, Davis, and UC Berkeley was published May 25 in Current Biology.

Professor Leah Krubitzer’s lab at the UC Davis Center for Neuroscience studies how evolution produces variation in brain organization across a wide variety of mammals, including opossums, tree shrews, rodents and primates. This comparative neurobiology approach shows how both evolution and development influence brain organization.

Although bats represent a quarter of all living mammalian species, this is the first time the full motor cortex of any bat has been mapped, said first author Andrew Halley, a postdoctoral researcher in Krubitzer’s lab.

The drug gabapentin may boost functional recovery after a stroke

These 3D images of mouse brain vasculature show normal conditions, top, and after an ischemic stroke, which occurs when a blood vessel clot blocks blood flow in the brain.
Credit: Andrea Tedeschi

The drug gabapentin, currently prescribed to control seizures and reduce nerve pain, may enhance recovery of movement after a stroke by helping neurons on the undamaged side of the brain take up the signaling work of lost cells, new research in mice suggests.

The experiments mimicked ischemic stroke in humans, which occurs when a clot blocks blood flow and neurons die in the affected brain region.

Results showed that daily gabapentin treatment for six weeks after a stroke restored fine motor functions in the animals’ upper extremities. Functional recovery also continued after treatment was stopped, the researchers found.

The Ohio State University team previously found that gabapentin blocks the activity of a protein that, when expressed at elevated levels after an injury to the brain or spinal cord, hinders re-growth of axons, the long, slender extensions of nerve cell bodies that transmit messages.

Neuroscientists Find Brain Mechanism Tied to Age-Related Memory Loss

As the brain ages, a region in the hippocampus becomes imbalanced, causing forgetfulness. Scientists say understanding this region of the brain and its function may be the key to preventing cognitive decline.

Working with rats, neuroscientists at Johns Hopkins University have pinpointed a mechanism in the brain responsible for a common type of age-related memory loss. The work, published in Current Biology, sheds light on the workings of aging brains and may deepen our understanding of Alzheimer's disease and similar disorders in humans.

"We're trying to understand normal memory and why a part of the brain called the hippocampus is so critical for normal memory," said senior author James Knierim, a professor at the university's Zanvyl Krieger Mind/Brain Institute. "But also with many memory disorders, something is going wrong with this area."

Neuroscientists know that neurons in the hippocampus, located deep in the brain's temporal lobe, are responsible for a complementary pair of memory functions called pattern separation and pattern completion. These functions occur in a gradient across a tiny region of the hippocampus called CA3.

In normal brains, pattern separation and pattern completion work hand-in-hand to sort and make sense of perceptions and experiences, from the most basic to the highly complex. If you visit a restaurant with your family and a month later you visit the same restaurant with friends, you should be able to recognize that it was the same restaurant, even though some details have changed—this is pattern completion. But you also need to remember which conversation happened when, so you do not confuse the two experiences—this is pattern separation.

Using Light and Sound to Reveal Rapid Brain Activity in Unprecedented Detail

The image shows the vasculature of the brain, and the colors illuminate how capillaries experience varying levels of oxygenation as the brain undergoes hypoxia.
Credit: Duke University

Duke researchers use a combination of hardware innovations and machine learning algorithms to create the fastest photoacoustic imaging tool available

Biomedical engineers at Duke University have developed a method to scan and image the blood flow and oxygen levels inside a mouse brain in real-time with enough resolution to view the activity of both individual vessels and the entire brain at once.

This new imaging approach breaks long-standing speed and resolution barriers in brain imaging technologies and could uncover new insights into neurovascular diseases like stroke, dementia and even acute brain injury.

The research appeared in the Nature journal Light: Science & Applications.

Imaging the brain is a balancing act. Tools need to be fast enough to capture rapid events, like a neuron firing or blood flowing through a capillary, and they need to show activity at different scales, whether it’s across the entire brain or at the level of a single artery.

Spying on Thousands of Neurons in the Brain’s Vision Center Simultaneously

Scientists tracked how individual neurons (white dots)
across the mouse visual center responded when the
animals saw an image on a screen.
That let the team trace the sequence
of events triggered when the eyes detect an important sight.
Credit: S. Ebrahimi et al./Nature 2022

Using a custom-built microscope to peer into the mouse brain, scientists have tracked the activity of single neurons across the entire visual cortex.

These recordings, made in the tenths of seconds after the animals saw a cue on a screen, expose the complex dynamics involved in making sense of what the eyes see. In an unprecedented combination of breadth and detail, the results describe the behavior of more than 21,000 total neurons in six mice over five days, Howard Hughes Medical Institute Investigator Mark Schnitzer’s team reports in the journal Nature on May 18, 2022.

His team is the first to get a glimpse of individual cells’ activity occurring at the same time throughout eight parts of the brain involved in vision. “People have studied these brain areas before, but prior imaging studies did not have cellular resolution across the entire visual cortex,” says Schnitzer, a neuroscientist at Stanford University.

The work highlights the dramatic sequence of events that unfolds in the brain from the instant it receives messages from the eyes until it decides how to respond to that sight. The researchers’ far-reaching but fine-grained imaging approach made it possible for them to collect an “incredible” set of data, says Tatiana Engel, a computational neuroscientist at Cold Spring Harbor Laboratory who was not involved in the study.

‘Resetting’ the injured brain offers clues for concussion treatment

Jonathan Godbout, professor of neuroscience
Credit: Ohio State University

New research in mice raises the prospects for development of post-concussion therapies that could ward off cognitive decline and depression, two common conditions among people who have experienced a moderate traumatic brain injury.

The study in mice clarified the role of specific immune cells in the brain that contribute to chronic inflammation. Using a technique called forced cell turnover, researchers eliminated these cells in the injured brains of mice for a week and then let them repopulate for two weeks.

“It’s almost like hitting the reset button,” said senior study author Jonathan Godbout, professor of neuroscience in The Ohio State University College of Medicine.

Compared to brain-injured mice recovering naturally, mice that were given the intervention showed less inflammation in the brain and fewer signs of thinking problems 30 days after the injury.

Though temporarily clearing away these cells, called microglia, in humans isn’t feasible, the findings shed light on pathways to target that could lower the brain’s overall inflammatory profile after a concussion, potentially reducing the risk for behavioral and cognitive problems long after the injury.

“In a moderate brain injury, if the CT scan doesn’t show damage, patients go home with a concussion protocol. Sometimes people come back weeks, months later with neuropsychiatric issues. It’s a huge problem affecting millions of people,” said Godbout, faculty director of Ohio State’s Chronic Brain Injury Program and assistant director of basic science in the Institute for Behavioral Medicine Research.

Researchers Discover New Function Performed by Nearly Half of Brain Cells

Scientists say the discovery of a new function by cells known as astrocytes opens a whole new direction for neuroscience research.
Illustration Credit: Siena Fried

Researchers at Tufts University School of Medicine have discovered a previously unknown function performed by a type of cell that comprises nearly half of all cells in the brain.

The scientists say this discovery in mice of a new function by cells known as astrocytes opens a whole new direction for neuroscience research that might one day lead to treatments for many disorders ranging from epilepsy to Alzheimer’s to traumatic brain injury.

It comes down to how astrocytes interact with neurons, which are fundamental cells of the brain and nervous system that receive input from the outside world. Through a complex set of electrical and chemical signaling, neurons transmit information between different areas of the brain and between the brain and the rest of the nervous system.

Until now, scientists believed astrocytes were important, but lesser cast members in this activity. Astrocytes guide the growth of axons, the long, slender projection of a neuron that conducts electrical impulses. They also control neurotransmitters, chemicals that enable the transfer of electrical signals throughout the brain and nervous system. In addition, astrocytes build the blood-brain barrier and react to injury.

But they did not seem to be electrically active like the all-important neurons—until now.

Five diseases attack language areas in brain

Each condition causes a different type of language impairment in primary progressive aphasia (PPA)

• Word comprehension is lost for some patients, others lose grammar
• Most extensive study to date on PPA
• Disease is often misdiagnosed in early stages, missing chance for treatment
• Not all dementia is caused by Alzheimer’s disease

There are five different diseases that attack the language areas in the left hemisphere of the brain that slowly cause progressive impairments of language known as primary progressive aphasia (PPA), reports a new Northwestern Medicine study.

“We’ve discovered each of these diseases hits a different part of the language network,” said lead author Dr. M. Marsel Mesulam, director of Northwestern’s Mesulam Center for Cognitive Neurology and Alzheimer’s Disease. “In some cases, the disease hits the area responsible for grammar, in others the area responsible for word comprehension. Each disease progresses at a different rate and has different implications for intervention.”

This study published in the journal Brain is based on the largest set of PPA autopsies — 118 cases — ever assembled.

“The patients had been followed for more than 25 years, so this is the most extensive study to date on life expectancy, type of language impairment and relationship of disease to details of language impairment,” said Mesulam, also chief of behavioral neurology at Northwestern University Feinberg School of Medicine.

Patients with PPA were prospectively enrolled in a longitudinal study that included language testing and imaging of brain structure and brain function. The study included consent to brain donation at death.

Wireless neuro-stimulator to revolutionize patient care

Many neurological disorders like Parkinson’s, chronic depression and other psychiatric conditions could be managed at home, thanks to a collaborative project involving researchers at the University of Queensland (UQ).

Queensland Brain Institute (QBI) Professor Peter Silburn AM said his team, together with Neurosciences Queensland and Abbott Neuromodulation have developed a remote care platform which allows patients to access treatment from anywhere in the world.

“By creating the world’s first integrated and completely wireless remote care platform, we have removed the need for patients to see their doctor in person to have their device adjusted,” Professor Silburn said.

Electrodes are surgically inserted into the brain and electrical stimulation is delivered by a pacemaker which alters brain function - providing therapeutic relief and improving quality of life.

This digital platform allows clinicians to monitor patients remotely, as well as adjust the device to treat and alleviate symptoms in real time.

“We have shown that it is possible to minimize disruption to patients’ and caregivers’ lifestyles by increasing accessibility to the service, saving time and money,” Professor Silburn said.

“There are no cures for many of these conditions which often require life-long treatment and care, so for those people the device would be a game-changer.”

He said the system also fostered increasingly personalized treatment and data-driven clinical decisions, which could improve patient care.

Newborn cells in the epileptic brain provide a potential target for treatment

Altered cells create an electrical “fire” in patients with epilepsy.
Credit: BioRender illustration by Aswathy Ammothumkandy/Bonaguidi Lab/USC Stem Cell

Over the years, everyone loses a few brain cells. A study led by scientists from USC Stem Cell and the USC Neurorestoration Center presents evidence that adults can replenish at least some of what they’ve lost by generating new brain cells, and that this process is dramatically altered in patients with long-term epilepsy. The findings are published in Nature Neuroscience.

“Our study is the first to detail the presence of newborn neurons and an immature version of a related cell type, known as astroglia, in patients with epilepsy,” said Michael Bonaguidi, an assistant professor of stem cell biology and regenerative medicine, gerontology, and biomedical engineering at USC. “Our findings furnish surprising new insights into how immature astroglia might contribute to epilepsy—opening an unexplored avenue toward the development of new anti-seizure medications for millions of people.”

First author Aswathy Ammothumkandy, who is a postdoctoral fellow in the Bonaguidi Lab, and her colleagues collaborated with USC neurosurgeons Charles Liu and Jonathan Russin, who often treat patients with seizures that can’t be controlled with medication. Drug resistance is particularly common with mesial temporal lobe epilepsy, or MTLE, and affects one-third of all patients with this form of the disease. As a result, some patients need to undergo surgery to remove the section of the brain, the hippocampus, that causes their seizures.

New Insights into the Neuroscience Behind Conscious Awareness of Choice

Nancy Smith participates in neuroscience experiments to play a digital piano using a brain-computer interface.
Credit: T. Aflalo

When you absentmindedly reach out to pick up your cup of coffee and take a sip, what happens in your brain? Many studies have shown that brain activity begins to ramp up even before you are aware of your choice to move. But this poses a conundrum: Do we have free will to make our own choices, if our brains are already preparing for actions before we are even conscious of them?

Now, a new study from the laboratory of Richard Andersen, James G. Boswell Professor of Neuroscience, and Leadership Chair and Director of the T&C Chen Brain–Machine Interface Center, gives new insights into how the brain encodes for our choices about movement. The research indicates that brain activity of abstract high-level choices (such as the desire to consume more coffee) connects to the actual actions (such as reaching out a hand) even before the awareness of such choices to move.

"The implementation of current brain-machine interfaces that read out the intent of patients assume that they are simultaneously consciously aware of the intent that is being decoded from their brains," says Andersen. "Taking into account this early subconscious activity is critical when designing algorithms for brain-computer interfaces that could one day enable people with spinal or brain damage to regain function."

Scientists discover genetic variants that speed up and slow down brain aging

Researchers from a USC-led consortium have discovered 15 “hot spots” in the genome that either speed up brain aging or slow it down — a finding that could provide new drug targets to resist developmental delays, Alzheimer’s disease and other degenerative brain disorders.

The research appeared online Tuesday in Nature Neuroscience.

“The big game-changer here is discovering locations on the chromosome that speed up or slow down brain aging in worldwide populations. These can quickly become new drug targets,” said Paul Thompson of USC, a lead author on the study and the co-founder and director of the ENIGMA Consortium. “Through our AI4AD [Artificial Intelligence for Alzheimer’s Disease] initiative we even have a genome-guided drug repurposing program to target these and find new and existing drugs that help us age better.”

ENIGMA is working group based at USC that is exploring a vast trove of brain data and has published some of the largest-ever neuroimaging studies of schizophrenia, major depression, bipolar disorder, epilepsy, Parkinson’s disease, and even HIV infection.

To discover the hot spots, or genomic loci, more than 200 ENIGMA-member scientists from all over the world looked for people whose brains were scanned twice with MRI. The scans provided a measure of how fast their brains were gaining or losing tissue in regions that control memory, emotion and analytical thinking.