Posts Tagged neurons

[WEB] New glial cells discovered in the brain: Implications for brain repair

Source: University of Basel

Summary: Neurons, nerve cells in the brain, are central players in brain function. However, a key role for glia, long considered support cells, is emerging. A research group has now discovered two new types of glial cells in the brain, by unleashing adult stem cells from their quiescent state. These new types of glia may play an important role in brain plasticity and repair.

FULL STORY


Neurons, nerve cells in the brain, are central players in brain function. However, a key role for glia, long considered support cells, is emerging. A research group at the University of Basel has now discovered two new types of glial cells in the brain, by unleashing adult stem cells from their quiescent state. These new types of glia may play an important role in brain plasticity and repair.

The brain is malleable well into adulthood. Brain plasticity is not only due to the formation of new nerve connections. Stem cells present in the adult brain also generate new nerve cells. For more than a hundred years, scientists have concentrated on investigating different types of nerve cells.

In the brain, however, another class of cells, called glia, are also essential for brain function. However, the importance of glial cells has been underestimated for decades. How many types of glia there are, how they develop and what roles they play are all still largely unexplored.

Stem cells — unleashed from quiescence

The research group of Prof. Fiona Doetsch at the Biozentrum of the University of Basel is investigating stem cells in the ventricular-subventricular zone in the adult mouse brain. In this region, many of the stem cells are in a quiescent state, sensing signals in the environment that stimulate them to awaken and transform into new nerve cells.

In their study in the journal Science, Doetsch’s team identified a molecular signal that awakened the stem cells from their quiescent state, allowing them to uncover multiple domains that give rise to glial cells in this stem cell reservoir.

Stem cells — birthplace of glial cells

“We found an activation switch for quiescent stem cells,” Doetsch explains. “It is a receptor that maintains the stem cells in their resting state. We were able to turn off this switch and thus activate the stem cells,” Doetsch says. In addition, the researchers were able to visualize the development of the stem cells into different glial cells in specific areas of the stem cell niche.

“Some of the stem cells did not develop into neurons, but into two different novel types of glial cells,” Doetsch reports. This brain region studied is therefore a birthplace for different types of glial cells as well as its role as a breeding ground for neurons.

“What was very unexpected was that one glial cell type was found attached to the surface of the wall of the brain ventricle, rather than in the brain tissue.” These cells are continuously bathed by cerebrospinal fluid and interact with axons from other brain areas, and therefore are poised to sense and integrate multiple long-range signals.

Glial cells — active in health and disease

The research team also found that both glial cell types were activated in a model of demyelination. These new glial cell types may therefore be a source of cells for repair in neurodegenerative diseases, such as multiple sclerosis or after injury.

As a next step, Doetsch would like to specifically trace these new glial cell types and to investigate their roles in normal brain function and how they respond in different physiological contexts. This will provide important clues to understanding brain plasticity and how the renewal and repair of neural tissue occurs.


Story Source:

Materials provided by University of BaselNote: Content may be edited for style and length.


Journal Reference:

  1. Ana C. Delgado, Angel R. Maldonado-Soto, Violeta Silva-Vargas, Dogukan Mizrak, Thomas von Känel, Kelly R. Tan, Alex Paul, Aviv Madar, Henar Cuervo, Jan Kitajewski, Chyuan-Sheng Lin, Fiona Doetsch. Release of stem cells from quiescence reveals gliogenic domains in the adult mouse brainScience, 2021; 372 (6547): 1205 DOI: 10.1126/science.abg8467

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[WEB] New glial cells discovered in the brain: Implications for brain repair

Summary: Neurons, nerve cells in the brain, are central players in brain function. However, a key role for glia, long considered support cells, is emerging. A research group has now discovered two new types of glial cells in the brain, by unleashing adult stem cells from their quiescent state. These new types of glia may play an important role in brain plasticity and repair.

FULL STORY

Neurons, nerve cells in the brain, are central players in brain function. However, a key role for glia, long considered support cells, is emerging. A research group at the University of Basel has now discovered two new types of glial cells in the brain, by unleashing adult stem cells from their quiescent state. These new types of glia may play an important role in brain plasticity and repair.

The brain is malleable well into adulthood. Brain plasticity is not only due to the formation of new nerve connections. Stem cells present in the adult brain also generate new nerve cells. For more than a hundred years, scientists have concentrated on investigating different types of nerve cells.

In the brain, however, another class of cells, called glia, are also essential for brain function. However, the importance of glial cells has been underestimated for decades. How many types of glia there are, how they develop and what roles they play are all still largely unexplored.

Stem cells — unleashed from quiescence

The research group of Prof. Fiona Doetsch at the Biozentrum of the University of Basel is investigating stem cells in the ventricular-subventricular zone in the adult mouse brain. In this region, many of the stem cells are in a quiescent state, sensing signals in the environment that stimulate them to awaken and transform into new nerve cells.

In their study in the journal Science, Doetsch’s team identified a molecular signal that awakened the stem cells from their quiescent state, allowing them to uncover multiple domains that give rise to glial cells in this stem cell reservoir.

Stem cells — birthplace of glial cells

“We found an activation switch for quiescent stem cells,” Doetsch explains. “It is a receptor that maintains the stem cells in their resting state. We were able to turn off this switch and thus activate the stem cells,” Doetsch says. In addition, the researchers were able to visualize the development of the stem cells into different glial cells in specific areas of the stem cell niche.

“Some of the stem cells did not develop into neurons, but into two different novel types of glial cells,” Doetsch reports. This brain region studied is therefore a birthplace for different types of glial cells as well as its role as a breeding ground for neurons.

“What was very unexpected was that one glial cell type was found attached to the surface of the wall of the brain ventricle, rather than in the brain tissue.” These cells are continuously bathed by cerebrospinal fluid and interact with axons from other brain areas, and therefore are poised to sense and integrate multiple long-range signals.

Glial cells — active in health and disease

The research team also found that both glial cell types were activated in a model of demyelination. These new glial cell types may therefore be a source of cells for repair in neurodegenerative diseases, such as multiple sclerosis or after injury.

As a next step, Doetsch would like to specifically trace these new glial cell types and to investigate their roles in normal brain function and how they respond in different physiological contexts. This will provide important clues to understanding brain plasticity and how the renewal and repair of neural tissue occurs.


Story Source:

Materials provided by University of BaselNote: Content may be edited for style and length.


Journal Reference:

  1. Ana C. Delgado, Angel R. Maldonado-Soto, Violeta Silva-Vargas, Dogukan Mizrak, Thomas von Känel, Kelly R. Tan, Alex Paul, Aviv Madar, Henar Cuervo, Jan Kitajewski, Chyuan-Sheng Lin, Fiona Doetsch. Release of stem cells from quiescence reveals gliogenic domains in the adult mouse brainScience, 2021; 372 (6547): 1205 DOI: 10.1126/science.abg8467

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[NEWS] Researchers develop a technique to predict epileptic seizures

Reviewed by Emily Henderson, B.Sc. Dec 18 2020

A third of epilepsy sufferers are resistant to treatment for this neurological disease that affects 1% of the population. The onset of seizures is unpredictable, and has been the subject of fruitless research since the 1970s. The unforeseeable nature of the disease means patients are forced to take medication and / or adjust their lifestyles.

Neuroscientists from the University of Geneva (UNIGE) and the University Hospital of Bern (Inselspital) – working with the University of California in San Francisco (UCSF) and Brown University in Providence – have succeeded in developing a technique that can predict seizures between one and several days in advance. By recording neuronal activity over at least six months using a device implanted directly in the brain, it is possible to detect individual cycles of epileptic activity and provide information about the probability of a future seizure. This approach, published in the journal Lancet Neurology, is remarkably reliable, and prospective clinical trials are now in the pipeline.

An epileptic brain can switch suddenly from a physiological state to a pathological state, characterized by a disturbance of neuronal activity which can cause, inter alia, convulsions typical of an epileptic seizure. How and why the brain swaps one state for another is still poorly understood, with the result that the onset of a seizure is difficult, if not impossible, to predict.

Specialists worldwide have been trying for over 50 years to predict seizures a few minutes in advance, but with limited success.”

Timothée Proix, Researcher, Department of Fundamental Neurosciences, University of Geneva Faculty of Medicine

Seizures do not appear to be preceded by any obvious warning signs that would make prediction easier. The frequency, depending on the individual, varies from once a year to once a day.

“It’s a huge problem for patients”, begins Maxime Baud, a neurologist at Inselspital. “This unpredictability is associated with a permanent threat that obliges patients to take medication on a daily basis. And in many cases, it prevents them from participating in certain sports. Living with this hanging over you can also affect your mental health”. Existing treatments are often difficult to bear: they depend on drugs with numerous potential side effects to reduce neuronal excitability and sometimes involve neurosurgery to remove the epileptic focus, i.e. the starting point of the brain seizures. Moreover, a quarter of patients do not respond to these treatments, meaning they have to learn to manage the chronicity of their disease.

Weather forecasting

Epileptic activity can be measured using cerebral electrical activity data recorded by electroencephalography. This can be used to identify interictal discharges – evanescent discharges that appear in between seizures without directly causing them. “We observe clinically that epileptic seizures recur in clusters and cyclically. To ascertain whether the interictal discharges can explain these cycles and forecast the onset of a seizure, we analyzed the data in greater detail,” continues Dr Baud.

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To do this, Baud collaborated with Vikram Rao, neurologist at UCSF, to obtain neuronal activity data collected over several years using devices implanted long-term in the brains of patients with epilepsy. After confirming that there were indeed cycles of cerebral epileptic activity, the scientists turned their attention to statistical analysis.

This approach helped highlight a phenomenon known as the “pro-ictal state” where the probability of the onset of a seizure is high. “As with weather disturbances, there are several time scales in epileptic brain activity”, points out Dr Baud. “The weather is influenced by the cycle of the seasons or day and night. On an intermediate scale, when a weather front approaches, the probability that it will rain increases for several days and is, therefore, better predictable. These three scales of cyclic regulation also exist for epilepsy.”

The right timeframe

The electrical activity in the brain is a reflection of the cellular activity of its neurons, more precisely their action potentials, electrical signals propagating along the neural network to transmit information. Action potentials are well known to neuroscientists, and their probability can be modelled using mathematical laws. “We adapted these mathematical models to the epileptic discharges to find out whether they heralded or inhibited a seizure”, explains Dr Proix.

To boost the predictive reliability, recordings of brain activity over very long periods were required. Using this approach, fronts with a high probability of seizure lasting several days could be determined for a majority of patients, making it possible to predict seizures several days in advance in some. With brain activity data collected over periods of at least six months, seizure prediction is informative for two-thirds of patients.

The analytical approach is sufficiently “light” to allow the transmission of data in real time on a server or directly on a microprocessor with a device small enough to be implanted in the skull. The researchers are now working in collaboration with the Wyss Center for Bio and Neuroengineering, based at Campus Biotech in Geneva, to develop a minimally invasive brain monitoring device to record the long-term data needed to forecast seizures. The device, which slips under the skin of the scalp, could give people with epilepsy the power to plan their lives according to the likelihood of having a seizure.

Source: University of Geneva

Journal reference: Proix, T., et al. (2020) Forecasting seizure risk in adults with focal epilepsy: a development and validation study. Lancet Neurologydoi.org/10.1016/S1474-4422(20)30396-3.

Tags: BrainDrugsEpilepsyEpileptic SeizureFrequencyHospitalMedicineMental HealthNeurological DiseaseNeurologyNeuronsNeurosurgeryResearchSeizureSkin

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[News] New noninvasive ultrasound neuromodulation technique for epilepsy treatment

Reviewed by Emily Henderson, B.Sc.May 15 2020

Epilepsy is a central nervous system disorder characterized by recurrent seizures resulting from excessive excitation or inadequate inhibition of neurons.

Ultrasound stimulation has recently emerged as a noninvasive method for modulating brain activity; however, its range and effectiveness for different neurological disorders, such as Parkinson’s Disease, Epilepsy and Depression, have not been fully elucidated.

Researchers from the Shenzhen Institutes of Advanced Technology (SIAT) of the Chinese Academy of Sciences developed a noninvasive ultrasound neuromodulation technique, which could potentially modulate neuronal excitability without any harm in the brain.

Low-intensity pulsed ultrasound and ultrasound neuromodulation system were prepared for non-human primate model of epilepsy and human epileptic tissues experiments, respectively.

The results showed that ultrasound stimulation could exert an inhibitory influence on epileptiform discharges and improve behavioral seizures in a non-human primate epileptic model.

Ultrasound stimulation inhibited epileptiform activities with an efficiency exceeding 65% in biopsy specimens from epileptic patients in vitro.

The mechanism underlying the inhibition of neuronal excitability could be due to adjusting the balance of excitatory-inhibitory (E/I) synaptic inputs by the increased activity of local inhibitory neurons. In addition, the variation of temperature among these brain slices was less than 0.64°C during the experimental procedure.

The study demonstrated for the first time that low-intensity pulsed ultrasound improved electrophysiological activities and behavioral outcomes in a non-human primate model of epilepsy and suppressed epileptiform activities of neurons from human epileptic slices.

It provided evidence for the potential clinical use of non-invasive low-intensity pulsed ultrasound stimulation for epilepsy treatment.

Source: Chinese Academy of Sciences Headquarters

Journal reference: Lin, Z., et al. (2020) Non-invasive ultrasonic neuromodulation of neuronal excitability for treatment of epilepsy. Theranosticsdoi.org/10.7150/thno.40520.

BiopsyBrainCentral Nervous SystemDepressionEpilepsyin vitroNervous SystemNeuromodulationNeuronsTheranosticsUltrasound

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[WEB SITE] Traumatic brain injuries could be healed using peptide hydrogels

Traumatic brain injury (TBI) –– defined as a bump, blow or jolt to the head that disrupts normal brain function –– sent 2.5 million people in the U.S. to the emergency room in 2014, according to statistics from the U.S. Centers for Disease Control and Prevention. Today, researchers report a self-assembling peptide hydrogel that, when injected into the brains of rats with TBI, increased blood vessel regrowth and neuronal survival.

The researchers will present their results at the American Chemical Society (ACS) Fall 2019 National Meeting & Exposition. ACS, the world’s largest scientific society, is holding the meeting here through Thursday. It features more than 9,500 presentations on a wide range of science topics.

“When we think about traumatic brain injuries, we think of soldiers and athletes,” says Biplab Sarkar, Ph.D., who is presenting the work at the meeting. “But most TBIs actually happen when people fall or are involved in motor vehicle accidents. As the average age of the country continues to rise, the number of fall-related accidents in particular will also increase.”

TBIs encompass two types of injuries. Primary injury results from the initial mechanical damage to neurons and other cells in the brain, as well as blood vessels. Secondary injuries, which can occur seconds after the TBI and last for years, include oxidative stress, inflammation and disruption of the blood-brain barrier. “The secondary injury creates this neurotoxic environment that can lead to long-term cognitive effects,” Sarkar says. For example, TBI survivors can experience impaired motor control and an increased rate of depression, he says. Currently, there is no effective regenerative treatment for TBIs.

Sarkar and Vivek Kumar, Ph.D., the project’s principal investigator, wanted to develop a therapy that could help treat secondary injuries.

We wanted to be able to regrow new blood vessels in the area to restore oxygen exchange, which is reduced in patients with a TBI. Also, we wanted to create an environment where neurons can be supported and even thrive.”

Biplab Sarkar, Ph.D., New Jersey Institute of Technology

The researchers, both at the New Jersey Institute of Technology, had previously developed peptides that can self-assemble into hydrogels when injected into rodents. By incorporating snippets of particular protein sequences into the peptides, the team can give them different functions. For example, Sarkar and Kumar previously developed angiogenic peptide hydrogels that grow new blood vessels when injected under the skin of mice.

To adapt their technology to the brain, Sarkar and Kumar modified the peptide sequences to make the material properties of the hydrogel more closely resemble those of brain tissue, which is softer than most other tissues of the body. They also attached a sequence from a neuroprotective protein called ependymin. The researchers tested the new peptide hydrogel in a rat model of TBI. When injected at the injury site, the peptides self-assembled into a hydrogel that acted as a neuroprotective niche to which neurons could attach.

A week after injecting the hydrogel, the team examined the rats’ brains. They found that in the presence of the hydrogel, survival of the brain cells dramatically improved, resulting in about twice as many neurons at the injury site in treated rats than in control animals with brain injury. In addition, the researchers saw signs of new blood vessel formation. “We saw some indications that the rats in the treated group were more ambulatory than those in the control group, but we need to do more experiments to actually quantify that,” Sarkar says.

According to Kumar, one of the next steps will be to study the behavior of the treated animals to assess their functional recovery from TBI. The researchers are also interested in treating rats with a combination of their previous angiogenic peptide and their new neurogenic version to see if this could enhance recovery. And finally, they plan to find out if the peptide hydrogels work for more diffuse brain injuries, such as concussions. “We’ve seen that we can inject these materials into a defined injury and get good tissue regeneration, but we’re also collaborating with different groups to find out if it could help with the types of injuries we see in soldiers, veterans and even people working at construction sites who experience blast injuries,” Kumar says.

via Traumatic brain injuries could be healed using peptide hydrogels

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[TED Talk] The brain may be able to repair itself — with help | Jocelyne Bloch – YouTube

Through treating everything from strokes to car accident traumas, neurosurgeon Jocelyne Bloch knows the brain’s inability to repair itself all too well. But now, she suggests, she and her colleagues may have found the key to neural repair: Doublecortin-positive cells. Similar to stem cells, they are extremely adaptable and, when extracted from a brain, cultured and then re-injected in a lesioned area of the same brain, they can help repair and rebuild it. “With a little help,” Bloch says, “the brain may be able to help itself.”

via The brain may be able to repair itself — with help | Jocelyne Bloch – YouTube

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[WEB SITE] Neuromodulation helps rehabilitate patients after a stroke

How neuromodulation helps patients recover after a stroke.

The neuromodulation methods can be brought to a new level and be effectively used in clinical practice only by taking these criteria into account. (Photo: Representational/Pixabay)

 The neuromodulation methods can be brought to a new level and be effectively used in clinical practice only by taking these criteria into account. (Photo: Representational/Pixabay)

Washington: The current approach used for brain stimulation to rehabilitate patients after a stroke does not look into the diversity of lesions and the individual characteristics of the brains of patients, finds a recent study.

The study was published in the journal ‘Frontiers in Neurology’. In recent decades, non-invasive neuromodulation methods such as electric and magnetic stimulation of various parts of the nervous system have been increasingly used to rehabilitate patients after a stroke.

Stimulation selectively affects different parts of the brain, which allows you to functionally enhance activity in some areas while suppressing unwanted processes in others that impede the restoration of brain functions.

This is a promising mean of rehabilitation after a stroke. However, its results in patients remain highly variable. The study authors argued that the main reason for the lack of effectiveness in neuromodulation approaches after a stroke is an inadequate selection of patients for the application of a particular brain stimulation technique.

According to the authors, the existing approach does not take into account the diversity of lesions after a stroke and the variability of individual responses to brain stimulation as a whole. Researchers proposed two criteria for selecting the optimal brain stimulation strategy. The first is an analysis of the interactions between the hemispheres.

Now, all patients, regardless of the severity of injury after a stroke, are offered a relatively standard treatment regimen. This approach relied on the idea of inter-hemispheric competition.

“For a long time, it was believed that when one hemisphere is bad, the second, instead of helping it, suppress it even more,’ explained Maria Nazarova, one of the authors of the article.

“In this regard, the suppression of the activity of the ‘unaffected’ hemisphere should help restore the affected side of the brain. However, the fact is that this particular scheme does not work in many patients after a stroke. Each time it is necessary to check what the impact of the unaffected hemisphere is, whether it is suppressive or activating,” said Nazarova.

The second criterion is the neuronal phenotype. This is an individual characteristic of the activity of the brain, which is ‘unique to each person like their fingerprints’. Such a phenotype is determined, firstly, by the ability of the brain to build effective structural and functional connections between different areas (connectivity).

Secondly, the individual characteristics of neuronal dynamics. This is the state of the neuronal system in which it is the most plastic and capable of change. The neuromodulation methods can be brought to a new level and be effectively used in clinical practice only by taking these criteria into account.

 

via Neuromodulation helps rehabilitate patients after a stroke

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[NEWS] Pill that reverses brain damage could be on the horizon

 

Researchers at the University of Pennsylvania have made important progress in designing a drug that could recover brain function in cases of severe brain damage due to injury or diseases such as Alzheimer’s.

brain cellsVitaly Sosnovskiy | Shutterstock

The work builds on a previous study where the team managed to convert human fetal glial cells called astrocytes into functional neurons. However, that required using a combination of nine molecules – too many for the formula to be translated into a clinically useful solution.

As reported in the journal Stem Cell Reports, the team has now successfully streamlined the process so that only four molecules are needed – an achievement that could lead to pill for repairing brain damage.

We identified the most efficient chemical formula among the hundreds of drug combinations that we tested. By using four molecules that modulate four critical signaling pathways in human astrocytes, we can efficiently turn human astrocytes — as many as 70 percent — into functional neurons.”

Jiu-Chao Yin, Study Author

The researchers report that the new neurons survived for more than seven months in the laboratory environment and that they functioned like normal brain cells, forming networks and communicating with one another using chemical and electrical signaling.

“The most significant advantage of the new approach is that a pill containing small molecules could be distributed widely in the world, even reaching rural areas without advanced hospital systems,” says Chen.

“My ultimate dream is to develop a simple drug delivery system, like a pill, that can help stroke and Alzheimer’s patients around the world to regenerate new neurons and restore their lost learning and memory capabilities,” he continued.

Now, the years of effort the team has put into simplifying the drug formula has finally paid off and taken the researchers a step closer towards realizing that dream.

via Pill that reverses brain damage could be on the horizon

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[WEB PAGE] Blue Brain Project releases first-ever digital 3D brain cell atlas

 

Like “going from raw satellite images to Google Earth”, the Blue Brain Cell Atlas allows anyone to visualize every region in the mouse brain, cell-by-cell – and freely download data for new analyses and modelling.

The first digital 3D atlas of every cell in the mouse brain provides neuroscientists with previously unavailable information on major cell types, numbers and positions in all of the 737 brain regions – which could massively accelerate progress in brain science. Released by EPFL’s Blue Brain Project and published in Frontiers in Neuroinformatics, the Blue Brain Cell Atlas integrates data from hundreds of whole brain tissue stains into a comprehensive, interactive and dynamic online resource that can continuously be updated with new findings. This groundbreaking digital atlas can be used for analyzing and further modeling specific brain areas, and is a major step toward a full simulation of the rodent brain.


A Cell Atlas for the Mouse Brain
► Read original article
► Download original article (pdf)
► Try the Blue Brain Cell Atlas


“Despite vast numbers of studies over the past century, cell numbers were still only available for 4% of mouse brain regions – and these estimates often varied by as much as three-fold,” says Blue Brain Project Founder and Director, Professor Henry Markram. “This has limited our efforts to study and model the brain. The Blue Brain Cell Atlas solves this problem and presents the best estimates for all regions of the entire mouse brain that we have today.”

“Knowing the circuit components and how they are arranged is an essential starting point for modelling the brain – just as demographic data are essential for modelling a country, for example,” explains lead author and creator of the Cell Atlas, Dr Csaba Erö.

Previous brain atlases consist of stacks of images of stained brain slices. Some show precise cell positions for the entire brain, while others show particular cell types; but none turns this valuable data into numbers and positions of all the cells in the brain.

This revolutionary step took five years to complete. Erö and colleagues integrated imaging data from the Allen Institute for Brain Science with a large number of other anatomical studies to calculate and validate the major types, numbers, and positions of cells in each area of the mouse brain – including all the regions where cell data was never obtained before.

“Our Cell Atlas is like going from rough maps and raw satellite images to exploring cities and geographical features in Google Earth,” says Blue Brain Section Manager, Dr Marc-Oliver Gewaltig. “It’s 3D, it’s high resolution, it’s searchable, it’s navigable, it’s annotated, it’s user-friendly – and it provides new information.”

Freely available online, the Blue Brain Cell Atlas allows users to visualize all the cells in any brain region, and download their numbers and locations. It distinguishes excitatory, inhibitory and some other types of neurons – as well as major types of non-neuronal cells called glia, which insulate and protect neurons. These data are invaluable for researchers trying to understand the structure and function of different brain regions or for building functional models of specific brain regions.

“It is also a great teaching aid: you can choose to display just the regions of interest and navigate through these down to the scale of individual cells, which are color-coded by morphology,” adds Gewaltig.

The Blue Brain Cell Atlas is dynamic – allowing researchers to contribute to and improve the atlas with any new data.

“The cell numbers, locations and subtypes can now be refined as data are integrated from new experiments,” explains Markram.

“Our message to brain researchers everywhere is: try it, use it, add data to it,” conclude the authors.


Original article: A Cell Atlas for the Mouse Brain

REPUBLISHING GUIDELINES: Open access and sharing research is part of Frontiers’ mission. Unless otherwise noted, you can republish articles posted in the Frontiers news blog — as long as you include a link back to the original research. Selling the articles is not allowed.

About EPFL’s Blue Brain Project

The aim of the EPFL’s Blue Brain Project, a Swiss brain initiative founded and directed by Professor Henry Markram, is to build accurate, biologically detailed digital reconstructions and simulations of the rodent brain, and ultimately, the human brain. The supercomputer-based reconstructions and simulations built by Blue Brain offer a radically new approach for understanding the multilevel structure and function of the brain.

Contributors and Funding

EPFL’s Blue Brain Project would like to thank the Allen Institute for Brain Science for the large array of publicly available data. This project has received funding from the European Union’s Horizon 2020 Framework Programme for Research and Innovation under Grant Agreement No. 604102 (Human Brain Project Ramp-Up Phase) and Grant Agreement No. 720270 (Human Brain Project SGA1). This work was supported by the EPFL Blue Brain Project Fund and the ETH Board Funding to the Blue Brain Project.

About EPFL

EPFL, one of the two Swiss Federal Institutes of Technology, based in Lausanne, is Europe’s most cosmopolitan technical university with students, professors and staff from over 120 nations. A dynamic environment, open to Switzerland and the world, EPFL is centered on its three missions: teaching, research and technology transfer. EPFL works together with an extensive network of partners including other universities and institutes of technology, developing and emerging countries, secondary schools and colleges, industry and economy, political circles and the general public, to bring about real impact for society.

 

via Blue Brain Project releases first-ever digital 3D brain cell atlas – Science & research news | Frontiers

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[WEB SITE] Neuroscientists unravel how two different types of brain plasticity work on synapses

 

The brain’s crucial function is to allow organisms to learn and adapt to their surroundings. It does this by literally changing the connections, or synapses, between neurons, strengthening meaningful patterns of neural activity in order to store information. The existence of this process – brain plasticity – has been known for some time.

But actually, there are two different types of brain plasticity at work on synapses. One is “Hebbian plasticity”; it is the one which effectively allows for the recording of information in the synapses, named after pioneering neuroscientist Donald Hebb. The other, more recently discovered, is “homeostatic synaptic plasticity” (HSP), and, like other “homeostatic” processes in the body such as maintaining a constant body temperature, its purpose is to keep things stable. In this case, HSP ensures that the brain doesn’t build up too much activity (as is the case in epilepsy) or become too quiet (as can happen when you lose synapses in Alzheimer’s Disease).

However, little is known about how these two types of plasticity actually interact in the brain. Now, a team of neuroscientists at the Champalimaud Centre for the Unknown, in Lisbon, Portugal, has begun to unravel the fundamental processes that happen in the synapse when the two mechanisms overlap. Their results were published in the journal iScience.

“In theory, the two types of plasticity act as opposing forces”, says Anna Hobbiss, first author of the new study, which was led by Inbal Israely. “Hebbian plasticity reacts to activity at the synapses by inciting them to get stronger while HSP reacts to it by making them weaker. We wanted to understand, on a cellular and molecular level, how the synapse deals with these two forces when they are present at the same time.”

In so doing, the authors have surprisingly shown that, contrary to what might be expected, HSP facilitates Hebbian plasticity, and thus influences memory formation and learning. This means that these two types of plasticity “may actually not be such distinct processes, but instead work together at the same synapses”, says Israely.

The team’s goal was to determine the changes in size of minute structures called dendritic spines, which are the “receiving end” of the synapse. The size of these spines changes to reflect the strength of the synaptic connection.

For this, they studied cells from the mouse hippocampus, a part of the brain which is crucial for learning. In their experiments, they blocked activity in the cells by introducing a potent neurotoxin called tetrodotoxin, thus simulating the loss of input to a certain part of the brain (“think about a person suddenly becoming blind, which leads to loss of input from the eyes to the brain”, says Hobbiss).

Forty eight hours later, they mimicked a small recovery of activity at only one synapse by releasing a few molecules of a neurotransmitter called glutamate on single spines of single neurons. This was possible thanks to a very high resolution, state-of-the-art laser technology, called two-photon microscopy, which allowed the scientists to very precisely visualize and target individual dendritic spines.

As this process evolved, the team closely watched what was happening to the spines – and they saw various anatomical changes. First, the silencing of all neural activity made the spines grow in size. “The spines are like little microphones, which, when there is silence, ramp up the ‘volume’ to try and catch even the faintest noise”, Hobbiss explains.

The scientists then activated individual spines with pulses of glutamate and watched them for two hours. One of the things they thought could happen was that the size of the spines would not grow further, since they had already turned up their ‘volume’ as far is it would go. But the opposite happened: the spines grew even more, with the smaller spines showing the biggest growth.

Finally, the authors also saw growth in neighboring spines, even though the experiment only targeted one spine. “We found that after a lack of activity, other spines in the vicinity also grew, further enhancing the cell’s sensitivity to restored neural transmission”, says Hobbiss. “The cells become more sensitive, more susceptible to encode information. It is as though the ‘gain’ has been turned up”, she adds.

“The fact that neighboring spines grew together with an active spine signifies that homeostatic plasticity changes one of the hallmark features of information storage, which is that plasticity is limited to the site of information entry”, Israely explains. “So, in this sense, the different plasticity mechanisms which are at work in the neuron can cooperate to change which and how many inputs respond to a stimulus. I think this is an exciting finding of our study.”

Taken together, these results show that homeostatic plasticity can actually rev up Hebbian plasticity, the type required for storing information. “Our work adds a piece to the puzzle of how the brain performs one of its fundamental tasks: being able to encode information while still keeping a stable level of activity”, concludes Hobbiss.

The misregulation of homeostatic plasticity – the stabilizing one – has started to be implicated in human health, specifically neurodevelopmental disorders such as Fragile X syndrome and Rett syndrome as well as neurodegenerative ones such as Alzheimer’s Disease. “Perhaps this balance is what allows us to be able to learn new information while retaining stability of that knowledge over a lifetime”, says Israely.

 

via Neuroscientists unravel how two different types of brain plasticity work on synapses

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