Allen Cell Types Database updated with new data and models

reposted from Allen institute

Allen Cell Types Database updated with new data and models

Updated computer models and new cells added to the database provide a robust look into the building blocks of the brain

March 16, 2017 | Download PDF

The Allen Institute for Brain Science has released additional data and computer models of cell activity for inclusion in the Allen Cell Types Database: a publicly available tool for researchers to explore and understand the building blocks of the brain.

“Comprehensive coverage of hundreds to thousands of cells will be crucial for scientists who want to explore the diversity of nerve cells in the brain, and provides a base from which we can parse cells into meaningful types,” says Lydia Ng, Ph.D., Senior Director of Technology at the Allen Institute for Brain Science. “This release is one more step in building a fundamental framework to help make advancements in neuroscience.”

Models serve as a critical link between observed data and theories about how cells work, enabling scientists to understand the mechanisms that give rise to neuron function. Two types of models have been added and updated as part of this release. The first set are models that reduce the complexity of neurons and use cell measurements to “predict” the activity and function of those cells, which are now available for 633 neurons in the database. Additionally, more sophisticated neuronal models based on cell shape, morphology and subcellular components are now available for hundreds of neurons via an interactive web browser.

The Allen Cell Types Database contains detailed descriptive features gathered from individual neurons in the mouse brain, including location, electrical activity and shape. For this release, electrophysiological recordings from an additional 130 cells from the cortex have been added to the database.

The Allen Cell Types Database (celltypes.brain-map.org) is a fundamental resource of the Allen Institute’s ten-year plan to understand how activity in the brain leads to perception, decision-making and action. Understanding cell types—the brain’s building blocks—is critical to making sense of both how the healthy brain functions and what goes wrong in diseases such as autism, Alzheimer’s and Parkinson’s.

Additional updates to Allen Brain Atlas resources are planned for June and October of 2017.

About the Allen Institute for Brain Science

The Allen Institute for Brain Science is a division of the Allen Institute (www.alleninstitute.org), an independent, 501(c)(3) nonprofit medical research organization dedicated to accelerating the understanding of how the human brain works in health and disease. Using a big science approach, the Allen Institute generates useful public resources used by researchers and organizations around the globe, drives technological and analytical advances, and discovers fundamental brain properties through integration of experiments, modeling and theory. Launched in 2003 with a seed contribution from founder and philanthropist Paul G. Allen, the Allen Institute is supported by a diversity of government, foundation and private funds to enable its projects. Given the Institute’s achievements, Mr. Allen committed an additional $300 million in 2012 for the first four years of a ten-year plan to further propel and expand the Institute’s scientific programs, bringing his total commitment to date to $500 million. The Allen Institute’s data and tools are publicly available online at www.brain-map.org.

reposted from

How Experience Shapes Adult Neurogenesis

Interneurons and mature granule cells in the adult mouse brain are critical for newborn neurons’ responses to novel environments.

By Ruth Williams | October 27, 2016

Granule neurons in the mouse dentate gyrusWIKIMEDIA, AVILA, J.Newly made cells in the brains of mice adopt a more complex morphology and connectivity when the animals encounter an unusual environment than if their experiences are run-of-the-mill. Researchers have now figured out just how that happens. According to a study published today (October 27) in Science, a particular type of cell—called an interneuron—in the hippocampus processes the animals’ experiences and subsequently shapes the newly formed neurons.

“We knew that experience shapes the maturation of these new neurons, but what this paper does is it lays out the entire circuit through which that happens,” said Heather Cameron, a neuroscientist at the National Institute of Mental Health in Bethesda who was not involved with the work. “It’s a really nicely done piece of work because they go step-by-step and show all of the cells that are involved and how they’re connected.”

Most of the cells in the adult mammalian brain are mature and don’t divide, but in a few regions, including an area of the hippocampus called the dentate gyrus, neurogenesis occurs. The dentate gyrus is thought to be involved in the formation of new memories. In mice, for instance, exploring novel surroundings electrically activates the dentate gyrus and can affect the production, maturation, and survival of the newly born cells. Now, Alejandro Schinder and his team at the Leloir Institute in Buenos Aires, Argentina, have investigated the process in detail.

Newborn dentate gyrus neurons, which are called granule cells, take six weeks to fully develop and integrate into the mouse brain’s existing neural networks, said Schinder. To examine these cells’ development, the team labeled newborn granule cells with red fluorescent protein in the brains of mice and then either left the animals in their regular cages (controls) or exposed them to enriched environments—cages with tunnels and other unusual objects—for different 48 hour periods. Three weeks after the new cells were labeled, the team examined their morphology and activity.

The researchers found that in animals who had been exposed to the enriched environment during a particular period (9 to 11 days after labeling), the young granule cells had longer dendrites with evidence of increased connections with other neurons. Specifically, these cells had a greater number of dendritic spines, the sites of incoming synapses, and more detectable electrical inputs.

Granule cells receive different inputs from surrounding neurons at different stages of their development, Schinder said, which may explain why they are apparently receptive to experiential input only within a short period (day 9 to 11), rather than throughout their development.

The team went on to analyze these neuronal inputs more closely. Through a series of optogenetic and chemogenetic experiments, the researchers showed that mature granule cells activated their younger counterparts via intermediary cells called interneurons. Artificially stimulating either the mature granule cells or the interneurons could recapitulate the effects of environmental enrichment on the young granule cells. Moreover, the team showed that blocking the activity of the interneurons during the animals’ exposure to enriched environments prevented the expected experience-induced morphology in the young granule cells.

“The take home message is that experience can change how these young cells are incorporating into the brain and how they are contributing to brain circuitry,” said Hongjun Song, who studies neurogenesis at the Johns Hopkins University School of Medicine in Baltimore and who did not participate in the research. But, he asked, “what’s the functional impact? Does this process make the mice better learners? Or if you block the process, do they get worse [at learning]?”

As yet, those questions remain unanswered.

D. D. Alvarez et al., “A disynaptic feedback network activated by experience promotes the integration of new granule cells,” Science, 354:459-65, 2016.

Tags

neuroscience, neurogenesis, learning, hippocampus and behavior

reposted from


D. D. Alvarez et al., “A disynaptic feedback network activated by experience promotes the integration of new granule cells,” Science, 354:459-65, 2016

How Experience Shapes Adult Neurogenesis

Interneurons and mature granule cells in the adult mouse brain are critical for newborn neurons’ responses to novel environments.

By Ruth Williams | October 27, 2016

Granule neurons in the mouse dentate gyrusWIKIMEDIA, AVILA, J.Newly made cells in the brains of mice adopt a more complex morphology and connectivity when the animals encounter an unusual environment than if their experiences are run-of-the-mill. Researchers have now figured out just how that happens. According to a study published today (October 27) inScience, a particular type of cell—called an interneuron—in the hippocampus processes the animals’ experiences and subsequently shapes the newly formed neurons.

“We knew that experience shapes the maturation of these new neurons, but what this paper does is it lays out the entire circuit through which that happens,” said Heather Cameron, a neuroscientist at the National Institute of Mental Health in Bethesda who was not involved with the work. “It’s a really nicely done piece of work because they go step-by-step and show all of the cells that are involved and how they’re connected.”

Most of the cells in the adult mammalian brain are mature and don’t divide, but in a few regions, including an area of the hippocampus called the dentate gyrus, neurogenesis occurs. The dentate gyrus is thought to be involved in the formation of new memories. In mice, for instance, exploring novel surroundings electrically activates the dentate gyrus and can affect the production, maturation, and survival of the newly born cells. Now, Alejandro Schinder and his team at the Leloir Institute in Buenos Aires, Argentina, have investigated the process in detail.

Newborn dentate gyrus neurons, which are called granule cells, take six weeks to fully develop and integrate into the mouse brain’s existing neural networks, said Schinder. To examine these cells’ development, the team labeled newborn granule cells with red fluorescent protein in the brains of mice and then either left the animals in their regular cages (controls) or exposed them to enriched environments—cages with tunnels and other unusual objects—for different 48 hour periods. Three weeks after the new cells were labeled, the team examined their morphology and activity.

The researchers found that in animals who had been exposed to the enriched environment during a particular period (9 to 11 days after labeling), the young granule cells had longer dendrites with evidence of increased connections with other neurons. Specifically, these cells had a greater number of dendritic spines, the sites of incoming synapses, and more detectable electrical inputs.

Granule cells receive different inputs from surrounding neurons at different stages of their development, Schinder said, which may explain why they are apparently receptive to experiential input only within a short period (day 9 to 11), rather than throughout their development.

The team went on to analyze these neuronal inputs more closely. Through a series of optogenetic and chemogenetic experiments, the researchers showed that mature granule cells activated their younger counterparts via intermediary cells called interneurons. Artificially stimulating either the mature granule cells or the interneurons could recapitulate the effects of environmental enrichment on the young granule cells. Moreover, the team showed that blocking the activity of the interneurons during the animals’ exposure to enriched environments prevented the expected experience-induced morphology in the young granule cells.

“The take home message is that experience can change how these young cells are incorporating into the brain and how they are contributing to brain circuitry,” said Hongjun Song, who studies neurogenesis at the Johns Hopkins University School of Medicine in Baltimore and who did not participate in the research. But, he asked, “what’s the functional impact? Does this process make the mice better learners? Or if you block the process, do they get worse [at learning]?”

As yet, those questions remain unanswered.

D. D. Alvarez et al., “A disynaptic feedback network activated by experience promotes the integration of new granule cells,” Science, 354:459-65, 2016.

Tags

neuroscience, neurogenesis, learning, hippocampus and behavior

Cortical Census

reposted from The Scientist

Cortical Census

Scientists document the characteristics and connections of mouse neocortical neurons to establish the most detailed microcircuit map to date.

By Ruth Williams | November 26, 2015

DANIEL BERGER, XIAOLONG JIANG, FABIAN SINZ, XAQ PITKOW, ANDREAS TOLIASThe morphology and electrophysiology of approximately 2,000 neurons in the visual cortices of adult mice have been catalogued, along with the connectivity between more than 11,000 possible pairs of these cells. The resulting census, published in the journal Science today (November 26), reveals a number of new interneuron cell types as well as hitherto unappreciated patterns of local connections.

“I’m incredibly enthusiastic about what these authors have done,” said neuroscientist Giorgio Ascoli of the Krasnow Institute for Advanced Study in Fairfax, Virginia, who was not involved in the work. “It’s a truly impressive tour de force in terms of optimization of every experimental and analytical detail.”

“The amount of work that went into this is really amazing,” agreed Arthur Toga, director of the Laboratory of Neuro Imaging in Los Angeles who also was not involved in the study. “They took a very detailed, typically small-sample approach and applied it to a big survey.”

The murine neocortex—the outermost part of the cerebral cortex—is involved in higher brain functions such as sensory perception, conscious thought, language and reasoning. To determine how such complex functions arise, researchers must first understand the neurons present in the tissue—their characteristics and their connections. Two main types of neurons—excitatory neurons, such as pyramidal cells, and inhibitory interneurons—are present in the neocortex, but while the pyramidal cells are fairly stereotypical and well characterized, the interneurons exhibit exceedingly diverse morphologies and there is no consensus as to how many different types exist, let alone how they interconnect.

Adding to the difficulty of studying interneurons is that they continue to develop throughout adolescence into young adulthood. Electrophysiological analyses, however, are generally performed on juvenile brain tissue specimens because they tend to be more tractable and resilient than adult samples.

Andreas Tolias at the Baylor College of Medicine in Houston and his colleagues decided to tackle these challenges head-on. “I know that others have been talking about it and thinking about it, but I guess we just decided to do it,” he told The Scientist. “We thought it was a lot of work, but it could be done.”

First, the researchers optimized an existing protocol for slicing and preparing adult brain tissue ensuring that they could robustly record electrophysiological data. They then pushed the recording potential to the limit by simultaneously probing eight cells in each brain slice. This technique, called octuple whole-cell recording, is “tremendously difficult and challenging,” said Hongkui Zeng of the Allen Institute for Brain Science in Seattle who did not participate in the study. “Only a few people in the world can do it well.”

The eight-way recordings enabled the team to study not only each of the cells’ electrophysiological behaviors, but also whether the cells were electrically communicating with others nearby and, if so, how.

Lastly the team perfected a technique for staining interneurons that revealed the full extent of their branching axon and dendrite morphologies. To document the cells’ morphologies, study coauthorXiaolong Jiang spent “many hours . . . manually tracing [them] under a microscope,” Tolias explained.

Based on the cells’ individual anatomies and electrophysiologies, the team identified 15 different types of interneuron, many of which had not previously been described.

After studying how these cells connected with one another, however, it was clear that the interneurons fell into three main connectivity subgroups. The first group, which the team called “master regulators,” connected with any other type of interneuron or excitatory neuron (pyramidal cells). The second group, called “pyramidal-neuron-targeting interneurons” (PTIs), connected with pyramidal cells as well as other interneurons of the same family—“their brothers, but not their cousins,” as Ascoli put it. And the third group, “interneuron-selective interneurons” (ISIs), interacted only with other types of interneuron—“their cousins, but not their brothers,” Ascoli said. These three connectivity rules were enough to explain nearly all the team’s data.

Although there may be additional types of interneurons with different connectivity patterns, the discovery of these three types of interneuron connection “provides a framework that is extraordinarily useful for relating different types of observations from different experiments and different groups,” said Toga.

For example, it is thought that miswiring of neuronal circuits may be at the root of a number of psychiatric disorders. Therefore, said Zeng, “this [paper] provides a starting point for us to compare disease circuits with normal circuits to see what are the abnormalities.”

X. Jiang et al., “Principles of connectivity among morphologically defined cell types in adult neocortex,” Science, 350: aac9462-1-10, 2015.

reported from here

Where and how are fear-related behaviours and anxiety disorders controlled?

21.11.2013 - PRESS RELEASE

Neurosciences, cognitives sciences, neurology and psychiatry

A team of researchers at Inserm led by Cyril Herry (Inserm Unit 862, “Neurocentre Magendie,” Bordeaux) has just shown that interneurons located in the forebrain at the level of the prefrontal cortex are heavily involved in the control of fear responses. Using an approach combining in vivo recordings and optogenetic manipulations in mice, the researchers succeeded in showing that the inhibition of parvalbumin-expressing prefrontal interneurons triggers a chain reaction resulting in fear behaviour. Conversely, activation of these parvalbumin interneurons significantly reduces fear responses in rodents. 

This research is published in the journal Nature

Some traumatic events may lead to the development of severe medical conditions such as anxiety disorders or posttraumatic stress disorder (PTSD).

Anxiety disorders have a prevalence of approximately 18% worldwide.

Despite successful treatments, some patients relapse, and the original symptoms reappear over time (fear of crowds, recurring nightmares, etc.). An understanding of the neuronal structures and mechanisms involved in this spontaneous recovery of traumatic responses is essential.

All observations made by researchers indicate that fear behaviours are controlled in the forebrain at the level of the dorsomedial prefrontal cortex. This control of fear behaviour is based on the activation of neurons in the prefrontal cortex that are in contact with specific areas of the amygdala.

Using an innovative approach combining electrophysiological recording techniques, optogenetic manipulations and behavioural approaches, the researchers were able to demonstrate that fear expression is related to the inhibition of highly specific interneurons—the parvalbumin-expressing prefrontal interneurons.

More specifically, inhibition of their activity disinhibits the activity of the prefrontal projection neurons, and synchronises their action.

Synchronisation of the activity of different neuronal networks in the brain is a fundamental process in the transmission of detailed information and the triggering of appropriate behavioural responses. Although this synchronisation had been demonstrated as crucial to sensory, motor and cognitive processes, it had not yet been examined in relation to the circuits involved in controlling emotional behaviour.

“Our results identify two complementary neuronal mechanisms mediated by these specific interneurons, which accurately coordinate and increase the neuronal activity of prefrontal projection neurons, leading to fear expression,” explains Cyril Herry. 

The identification and better understanding of these neuronal circuits controlling fear behaviour should allow the development of new treatment strategies for conditions such as posttraumatic stress disorder and anxiety disorders. “We could, for example, imagine the development of individual markers for these specific neurons, or the use of transmagnetic stimulation approaches to act directly on excitatory or inhibitory cells and reverse the phenomena.”

How is fear analysed in an animal?

From an experimental standpoint, the classic Pavlovian conditioning procedure involves associating one stimulus, such as a sound, with another, unpleasant stimulus, such as a small electric shock. This first step allows the animal to establish a persistent aversive memory. In other words, the animal comes to remember and learn that the sound is associated with an unpleasant state, and an immobility response is routinely triggered, which is a good indication of fear in an animal.

In the second step, the extinction procedure involves repeated presentation of the sound alone, inducing a temporary inhibition of the conditioned fear responses. This inhibition is only temporary, as the mere passage of time favours the spontaneous recovery of the conditioned fear responses, which, from the clinical standpoint, may be associated with the phenomenon of relapse into traumatic responses seen following the treatment of posttraumatic stress disorder using exposure-based therapies.

TO CITE THIS PAGE :
Press release – Inserm press room – Where and how are fear-related behaviours and anxiety disorders controlled?

Link :
http://presse-inserm.fr/en/where-and-how-are-fear-related-behaviours-and-anxiety-disorders-controlled/10232/