Reshaping the brain: scientists reprogram neurons after birth

Pyramidal neurons have a distinctive shape and set of connections.

The cerebral cortex—the gray matter that forms the outer layers of the mammalian cerebrum and cerebellum—is divided into six different layers based on the presence of specialized neurons, and we've known that since the early 1900s. Denis Jabaudon is interested in using the tools of modern biology to understand the genetic mechanisms that establish and maintain those layers. Over the past few years, his lab has published papers implicating various genes in the generation of specific neuronal subtypes.

Now they have gone a step further. They have developed a new electrochemical method to transfer genes into specific types of neurons—they call it iontoporation. Using it, they have transformed one type of neuron in a mature brain into a different type entirely. (Imagine a lightning bolt and crash of thunder here to indicate how momentous and scary this is.) Just kidding—it’s not actually scary. Instead, it tells us something about the ability of a mature brain to adapt to being rewired.

Although Jabaudon and others have made some headway in working out how the different neurons arise, they still don’t know how plastic they are—if they can change fates after they started differentiating down one particular path. In the context of brain injury, it would be useful to know if certain neural circuits could be reprogrammed and repaired by having the neurons that are already present change fates to adapt to the damage. But this has been challenging to determine, because changing the fate of specific neurons in the latter stages of differentiation has been technically difficult.

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Experiencing math anxiety may be like the experience of physical pain

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For many of us, anxiety about math performance isn't so much a question of whether it will happen, but at what level of math it kicks in (in my case, Calculus III, sophomore year in college). But, as the authors of a new paper on math anxiety point out, most forms of higher math didn't even exist until a few centuries ago. It's very unlikely that this sort of anxiety has evolved a specialized brain structure dedicated to it. So, the researchers used a combination of math quizzes and functional MRI scans to identify the areas of the brain associated with the fear of math.

It turned out to be one that was previously associated with the experience of physical pain. And it doesn't appear to be the first time that area has been borrowed for other purposes by evolution: it also helps register the discomfort of social rejection.

The test the authors devised was pretty ingenious. First, they took their subjects (28 total) and divided them based on their level of distaste for math, using a series of questions termed the Short Math Anxiety Rating-Scale, or SMARS. Then, they put them in the MRI tubes and exposed them to a series of quizzes, some math focused, others targeting verbal skills. To trigger anxiety, a small warning indicator changed color based on the nature of the next test: a yellow circle indicated math was on its way, while a blue square indicated verbal questions would follow.

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Kavli awards go to perception researchers and Pluto killers

This morning, in conjunction with the start of New York's World Science Festival, the Kavli Foundation announced the winners of its third set of awards, honoring research in three fields: nanoscience, astrophysics, and neurobiology. THe three fields have a few things in common: they often involve research that crosses traditional boundaries between disciplines, they've all seen impressive progress in recent years, and they don't fit neatly into the subject areas honored by the Nobel Prizes.

The neuroscience prize was a bit of a grab-bag, united under the umbrella of perception. Cori Bargmann of Rockefeller University was honored for her work with C. elegans, a small worm that enables researchers to do both complex genetic experiments and track the fate of every single cell. Bargmann helped identify the neural circuits that lets the worm respond to changes in its environment. Ann Graybill was cited for her work with primates, where she helped identify the circuits involved in learning habits.

Winfried Denk is the odd one out, in that he's cited for developing techniques. One is a form of electron microscopy that gave an unprecedented view of the wiring of the brain. The second, called multi-photon microscopy, lets scientists image live cells by turning some of the molecules they normally contain into convenient fluorescent labels.

Paralyzed woman controls robotic arm, sips coffee

A tetraplegia controls a robotic arm, allowing herself to have a drink.

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Performing even a simple movement is a rather complicated process. First, the brain has to signal its intent to perform an action, which then gets translated into the specific motions that are required to achieve that intention. Those motions require a series of muscle contractions; the signals for these need to be sent out of the brain, through the spinal cord, and to the appropriate destination.

For most people who suffer from paralysis, it's really these later steps that are affected—most of the setup can still go on in the brain, but damage keeps the signals from making their way to the muscles. If there were a way to eavesdrop on the brain, it might be possible to identify an individual's intent and translate that into some form of useful action.

This may sound like science fiction, but significant progress has been made in the area. As far back as 2006, researchers were already reporting that electrodes placed in a person's motor cortex would allow them to manipulate an on-screen object in a three-dimensional environment. More recently, monkeys with a similar implant were hooked up to a robotic arm, which they learned to use to perform some simple tasks.

Adaptation without genetic changes help an octopus handle freezing temps

Humans may be able to live in a variety of climates, but we've discovered all sorts of creatures that can survive at temperatures that would kill us in short order. Genetic changes have allowed animals to adapt to temperatures that range from blazingly hot to right around freezing. In today's issue of Science, researchers describe how species of octopus that live in the frigid waters of the poles manage to keep their nerve cells working despite the chill. Instead of genetic changes, however, this adaptation relies on a process that edits the genetic information before it's made into a protein, a form of genetic editing that may be driven by the temperature difference itself.

It's not easy to survive at temperatures that hover at or below freezing, which will slow down many of the metabolic reactions that keep cells alive. But for multicellular organisms, the challenges are a bit more extensive, as they have to keep nerve cells firing at a reasonable clip. These nerve cells depend on a set of proteins, called voltage-gated channels, that we know change their behavior at low temperatures.

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A drug that activates only your father’s version of a gene may treat neural disorder

Anyone who's passed basic biology knows that we get one copy of a gene from our mother, a second from our father. But few people realize that not all of these genes end up being treated equally. Imprinted genes are expressed from only the maternal or paternal allele, rather than both. And, when this process goes wrong, it can actually lead to diseases. Now, researchers have identified a possible way to treat imprinting errors.

In the brain, Ube3a is an imprinted gene; only the maternal allele is expressed, even if it is mutated and the paternal allele is normal. This is the case in Angelman syndrome, a severe neurodevelopmental disorder caused by mutation or deletion of the maternal allele of Ube3a. Ube3a is imprinted only in the brain, though; in other tissues, the paternal allele is expressed along with the maternal one.

This led Benjamin Philpot and his colleagues at UNC Chapel Hill to wonder: wouldn’t it be great if we could get the normal, paternal version of Ube3a to work in the brain—to unsilence it? Maybe this could help kids with Angelman syndrome.

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Naked mole rats feel no pain due to acid

African naked mole rats never cease to amaze. Not only are they exceedingly ugly, but they are the longest living rodents. Moreover, none have ever been observed to get cancer. And they are the only known vertebrates that are not bothered by acid. A report in this week’s Science explains the molecular basis underlying this acid insensitivity, and suggests that it might be an adaptation to their oxygen-poor living conditions..

Acid causes pain by activating nociceptors, proton-triggered ion channels that activate neurons. This recent study compared acid receptors from naked mole rats and mice, and found that they were not all that different. Similar numbers of each receptor were found in the respective animals, and acid evoked similar levels of current through them.

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Researchers study autism by making stem cells from autistic patients

Autism, like other complex neuronal disorders, is usually attributable to the interaction of multiple genetic and environmental factors that have been extremely difficult to tease apart. People with Timothy syndrome suffer from hypoglycemia, cardiac arrhythmia, and global developmental delay; more than 60 percent of them also have an autism spectrum disorder (ASD). Researchers in California and Japan recently generated stem cells from people with Timothy syndrome and began differentiating them into neurons in an attempt to gain further insights into autism. Their results are published in Nature Medicine.

Timothy syndrome is caused by a genetic mutation that changes one amino acid in a calcium channel expressed in the brain—calcium influx through these channels is essential for neuronal processes. It is not yet known how the mutation that causes Timothy syndrome disrupts normal cellular functioning or how it leads to psychiatric symptoms. Timothy syndrome thus provides a good system for examining how a specific gene contributes to brain development.

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Bees reach consensus by headbutting dissenters

The human brain is wonderfully complex. Within it, there are billions of neurons, each collecting information and determining whether to respond to it. In some cases, groups of neurons compete for an outcome; when a group reaches a certain level of activity, its output ends up being chosen. To help make their case, these neurons can send positive signals to each other, and they can inhibit others with different agendas. Ideally, this system improves the chances of reaching an optimal decision; it’s an elegant way to make sense of lots of competing input.

As if we didn't think bees were cool enough already, Science reports this week that this approach to decision making is echoed in the behavior of honeybee swarms. Just as our neurons emit inhibitory signals, bees can hinder other hivemates that are advocating a different course of action. As with neurons, the swarm’s collective decision is made when a particular threshold is reached. But, unlike neurons, the bees have a very physical means of inhibiting those with a competing message: they headbutt them.

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