Allen Cell Types Database updated with new data and models

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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.

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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.

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neuroscience, neurogenesis, learning, hippocampus and behavior

Extra Eyeballs on the Eye

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Extra Eyeballs on the Eye

A legion of citizen-scientist gamers helps a team of researchers explain a long-standing riddle of how the retina processes motion.

By Rina Shaikh-Lesko | May 6, 2014

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WIKIMEDIA, AMY LEE ROBINSONResearchers have solved a 50-year mystery of how the retina processes motion with the aid of citizen scientists playing an online game, according to a study published this week (May 4) in Nature. A team led by Sebastian Seung of MIT found that two bipolar neurons in the retina firing together activate a third neuron, a starburst amacrine cell, which is wired to the brain.

Initially, scientists thought the eye passed all visual information for processing up to the brain. Since the mid-1960s, though, researchers have realized that the retina is sensitive to direction and speed.

Seung is the creator of a neuron-mapping game called EyeWire. More than 120,000 gamers from 140 countries helped Seung’s team to map and color-code individual neurons and their connections in the retina. The researchers used retinal neuron wiring diagram created by the players and pieced together by Seung’s team to understand what was going on inside the retina.

“This is a very nice paper that poses a very clear and testable prediction about direction-selective computation in the retina,” neuroscientist Botond Roska from the Friedrich Miescher Institute for Biomedical Research in Basel, Switzerland, who was not involved in the study, told Nature News. “It’s an exciting idea, and I bet it’ll be followed by research from many labs trying test this hypothesis.”

Seung noted that the wiring diagram depicts a small fraction of the total neural connections in the retina. “There are probably other neurons that are a part of this motion-detection circuit,” he told Nature. “We need to map those out and eventually reconstruct the entire retinal connectome.”