Astrocytes rule!

Mice that received transplants of human glial progenitor cells learned much more quickly than normal mice, according to a study published today (March 7) in Cell Stem Cell. The findings support the theory that glial cells made a significant contribution to the evolution of our own enhanced cognitive abilities.

This work is surprising because it demonstrates that there may be something special about human glial cells that contribute to the complexity and computational abilities of the human brain.  For many years, glia cells, non-neuronal cells present in the same numbers as neurons in the brain, were thought to play only a supporting role, providing structure, insulation, and nutrients for neurons. But in the past 20 years it has become clear that glia also participate in the transmission of electrical signals. Specifically, astrocytes—a type of glial cell with thousands of tendrils that reach and encase synapses—can modulate signals passing between neurons and affect the strength of those connections over time.

Recent studies have also demonstrated that human astrocytes are very different from those found in mouse and rat brains, on which most previous studies of astrocyte physiology were based. Human astrocytes are more numerous, larger, and more complex, and they are capable of far more rapid signaling responses than rodent astrocytes.

Together, these results suggest that astrocytes may have been critical to the evolution of enhanced neural processing in humans. Having already transplanted human glial progenitor cells (GPCs) to restore myelination in myelin-deficient mice, Steven Goldman of University of Rochester Medical Center in New York and colleagues realized that they could repeat the trick in normal mice to assess the contribution of human-specific astrocytes to synaptic plasticity and learning.

Goldman’s team grafted human GPCs into the brain of baby mice and waited until they became adults, by which time a large proportion of their forebrain glia were replaced by human cells differentiated from the GPCs, including astrocytes with the same structure and functional capabilities as in humans. The researchers then looked at long-term potentiation (LTP)—the strengthening of synaptic connections and a key mechanism underlying learning—in the hippocampus, and found that it was significantly enhanced in mice with human GPCs compared with normal mice and mice engrafted with mouse GPCs. Goldman and colleagues also assessed the performance of the mice on several behavioral tasks that measure learning and memory—including auditory fear conditioning, a maze test, and object-location memory—and found across the board that mice with human GPCs learned significantly more quickly than normal mice.

The human glial progenitor cells implanted in the mouse brain caused enhanced learning, something that most neuroscientists, including those that focus on glia, would not have predicted.  Exploring potential molecular mechanisms behind such an effect, Goldman and his colleagues noticed significant increases in the release of a cytokine called TNFa in the human-derived astrocytes in mice. And when they blocked the production of this molecule, LTP was reduced, as was performance in the object-location memory task, suggesting that TNFa is an important player in the glia-mediated enhancement of synaptic function.  

Goldman says that the results provide “a substantial clue” to the basis of human smartness. “We now have to view the evolution of glial form and function as one of the most important aspects of human cognitive evolution,” said Goldman.

Furthermore, having reported in February that they can generate human GPCs from skin cells reprogrammed into induced pluripotent stem cells, Goldman’s team can now make patient-specific GPCs from individuals with neuropsychiatric and neurological diseases thought to be specific to humans or primates—and therefore potentially glial-associated. By implanting these cells into normal mice, the researchers can create in vivo models with which to investigate the role of glial cells in these disorders.

“This gives us a broad platform to sort out the differential contribution of glia and neurons in certain diseases,” said Goldman, who is already analyzing data from such experiments on schizophrenia and Huntington’s disease. “Most current therapeutics target neurons, but this gives us the potential to develop glial targets for new drugs.”

X. Han et al., “Forebrain engraftment by human glial progenitor cells enhances synaptic plasticity and learning in adult mice,” Cell Stem Cell, 12:342-53, 2013.

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Universal Flu Vaccines Charge Ahead | The Scientist Magazine®

Universal Flu Vaccines Charge Ahead | The Scientist Magazine®.

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Awesome! Birds of Paradise

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Suddenly There’s A Meadow In The Ocean With ‘Flowers’ Everywhere : Krulwich Wonders… : NPR


Suddenly There’s A Meadow In The Ocean With ‘Flowers’ Everywhere : Krulwich Wonders… : NPR.

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Curious Behavior

image: Curiouser and Curiouser

After thousands of years of contemplating and studying the human condition, it is shocking how little attention has been paid to our most common, and in some ways defining, behaviors.

In Curious Behavior, Robert Provine provides clear, entertaining, and (most importantly) data-driven accounts of familiar yet overlooked human quirks. These include yawning, laughing, crying, tears, coughing, sneezing, hiccupping, vomiting and nausea, tickling, itching and scratching, farting and belching, and finally prenatal behavior.

Many of the investigations are part of Provine’s own, pioneering studies—we read about much of the research from the horse’s mouth, and skeptics are encouraged to conduct their own “sidewalk neuroscience” experiments. This is a refreshing reminder of how science can be done on a small budget, without elaborate equipment. The research includes controlled laboratory studies, observations of non-human primates, interviews with other scientists, and much sleuthing through the literature. But there are also urban safaris.  Provine stalks modern Homo sapiens in their natural habitat—the local mall, a party, an office, or the classroom—observing new aspects of human behavior hidden in plain sight. The approach is reminiscent of the classical ethology studies of Lorenz, Tinbergen, and von Frisch.

We learn that we sometimes behave as herd animals, with our eyes often communicating more than our mouths. We “catch” contagious yawns, laughter, and sometimes scratching, crying, and even vomiting. Tears are revealed as a uniquely human form of social communication without which sad human faces can be ambiguous. Most laughter occurs in the absence of humor, but pant-pant vocalizations by playful primates reveal the likely origins of this social signal.

Written with humor and wit, Curious Behavior is an accessible and entertaining read with its musings about the theoretical Doomsday yawn, ineffectual astronaut tears, and the social implications of coughing and laughter. But it is also serious science about the importance of defining stimuli and understanding the difference between what people think they do, and what they actually do.

The book may provide new windows into autistic behaviors, schizophrenia, and the definition of self. It also includes important lessons for students and young investigators. One is to “appreciate straight, jargon-free talk about everyday things, and abhor florid neurologizing and biologizing, the dressing up of behavioral accounts in the trappings of neurology and biology to provide the illusion of depth and substance.”

In a world where there is an increasing gulf between the public and scientists, Provine leads by example with straightforward science communication. Other lessons he shares are timeless, harking back to the renowned neuroanatomist Ramon y Cajal in his 1897 Advice to Young Investigators, such as the pitfall of thinking that all key problems in science have been solved, or the importance of avoiding “instrument addicts”—those with impressive machinery but few ideas. This book is a must-have for any connoisseur of human behavior.

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Top Scientists of 2012

What scientists received prestigious science awards this year?

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How Insulin Works

Insulin cartoon

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