CLARITY Makes Brains “See-Through”
The science community received big news out of California last week as Karl Deisseroth and his team of researchers from the Department of Bioengineering at Stanford University had their paper concerning their newly developed CLARITY brain imaging technique published in Nature. The most astounding aspect of the newly released technique is that is creates a “see-through” brain that can be anatomically analyzed in a number of ways. This method truly is a game-changer as it revolutionizes how neuroscientists are able to view brain tissue and allows for a clearer view of the big picture. In this case the big picture is an intact, whole brain.
The technique operates on the idea lipids in the bilayer of a cell’s plasma membrane block visible light. This is why the brain is normally not transparent. Removing these lipids but still keeping the other parts of the cell and its environment intact would render the brain “see-through” and allow for much easier imaging of large pieces of brain tissue, if not the whole brain at once. This idea is carried out by taking the brain and infusing it with acrylamide, which binds proteins, nucleic acids and other molecules, then heating the tissue to form a mesh that holds the tissue together. The brain is then treated with SDS detergent to remove the light-blocking lipids resulting in a stable brain-hydrogel hybrid. From here the transparent tissue can be fluorescently labeled for certain cells and analyzed. Through the whole process there is less than 10% protein loss in the brain tissue compared to around 41% for other current methods. This is an amazing improvement!
Example of brain image produced by CLARITY from neurons in an intact mouse hippocampus. (http://med.stanford.edu/ism/2013/downloads/CLARITY/CLARITY_stained.jpg)
New Methods in Brain Scans to Examine Running Rats and Flying Bats
Researchers from the U.S. Department of Energy’s Brookhaven National Laboratory and Thomas Jefferson National Accelerator Facility, Oak Ridge National Laboratory, Johns Hopkins Medical School, the University of Maryland, and Weizmann Institute’s Neurobiology Department have all developed new and improved brain scanning techniques. These new methods allow scientists to monitor brain activity in fully-awake, moving animals.
At Brookhaven, researchers combined light-activated proteins that stimulate specific brain cells, a technique known as optogenetics, with positron emission tomography (PET) to observe the effects of stimulation throughout the entire brain. Their paper in the Journal of Neuroscience describes this method, which will allow researchers to map exactly which neurological pathways are activated or deactivated downstream by stimulation in specific brain areas. Hopefully, following these pathways will enable researchers to correlate the brain activity with observed behaviors or certain symptoms of disease.
Three markers on the head of a mouse enable the AwakeSPECT system to obtain functional images of the brain of a conscious mouse as it moves around. (Credit: Image courtesy of DOE/Thomas Jefferson National Accelerator Facility)
A Brave New World: You
The Pasteurian Revolution of the 1800′s heralded in a new paradigm of disease. Previously unexplained health phenomena could now be shown to be derived from “germs” – microorganisms invisible to the naked eye. The term “germ” quickly took on a negative connotation and until recently the microbial world has been seen primarily as a breeding ground for invisible enemies to human health. Its pretty incredible actually, the distaste the word “bacteria” instills in us, when really, it simply refers to a domain of prokaryotes. So, is the entire microbial world bent on our demise? I think the answer to this question can be summed up in one simple statistic:
Inside of you there are 1013 human cells and 1014 bacteria cells.
In other words, for every one cell of you there are ten that are not you…Wait, what? The first question this recent discovery may fuel is a stumbled WHAT? But lets digress for a moment and ask, why?
Obama’s BAM Project Becomes BRAIN Initiative
At his State of the Union address nearly two months ago, President Obama announced plans for the Brain Activity Map (BAM) project (see The Nerve blog Part 1 and Part 2), a billion-dollar ten-year research initiative to gain a better understanding of the brain and to provide deeper insights into diseases like Alzheimer Disease, Parkinson Disease, and Autism Spectrum Disorder.
On Tuesday, April 2nd, the President announced that he plans to include the BAM project – now termed the BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative – in his 2014 budget proposal. The director of the NIH, Dr. Francis Collins, notes that one of the major goals of the project is to simultaneously sample from many neurons in real-time. Although existing technology can measure the activities of single neurons and of brain regions, it cannot measure those of circuits. Because existing technology has not yet advanced to a level that allows such complex analysis, the BRAIN initiative will be initially funded $100 million for the year of 2014 to develop and advance neuroscience technologies. Yearly negotiations will take place to determine future funding.
Don’t Panic! – Mice Aren’t Actually the Smartest
“Man had always assumed that he was more intelligent than dolphins because he had achieved so much — the wheel, New York, wars and so on — whilst all the dolphins had ever done was muck about in the water having a good time. But conversely, the dolphins had always believed that they were far more intelligent than man — for precisely the same reasons….In fact there was only one species on the planet more intelligent than dolphins, and they spent a lot of their time in behavioural research laboratories running round inside wheels and conducting frighteningly elegant and subtle experiments on man. The fact that once again man completely misinterpreted this relationship was entirely according to these creatures’ plans.” – Douglas Adams, The Hitchhiker’s Guide to the Galaxy
As tempting as it may be to believe the science fiction version of the intelligence rankings, real-life science has spoken and suggests (much to my displeasure) that humans may actually be the highest on the intelligence scale.
Ketamine: Kan it Kure Depression?
Affective disorders are those disorders of the brain that are characterized by severe and inappropriate shifts in mood or emotion. These shifts are often to extreme ends of the emotional spectrum where an affected individual is constantly full of energy and confidence (mania) or withdrawn, fatigued, and excessively sad with little interest in usually enjoyable activities (depression). Both of these conditions have been observed and recorded in human history for thousands of years but only recently have they been recognized as brain disorders, given names like major depression and bipolar disorder, and treated as medical conditions.
In the past 150 years it has been noted that the onset of depression is occurring at higher rates and at younger ages that ever before. This data could be the result of factors including an increase in patients coming forward to be diagnosed, improved diagnoses, or simply better record keeping. Whatever the reason, it is estimated that 15 to 20% of the population is experiencing symptoms of major depression at any given time, with a greater occurrence in women than in men. Many are affected by this disorder and a cure has yet to be found. But before we continue, a distinction must be made between major depression and “reactive depression” in which a person may feel depressive symptoms because of a single event like the loss of a loved one or a failure of some kind. Major depression is a prolonged state in which an individual may display a number of symptoms including depressed mood, loss of interest in most activity, change in body weight or appetite, changes in sleep patterns, psychomotor agitation or retardation, fatigue, difficulty concentrating, feelings of worthlessness or guilt, and suicidal thoughts. Depending on the severity of the depression a patient may display many, or only a few of these possible symptoms.
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The Birds
In my vision modeling class this week, we were learning about the structure of the (primate) visual cortex and one of my classmates posed an interesting question: how is it that birds sustain such amazing visual acuity when they don’t seem to have the cortical volume to process that detailed information? In other words, how does a bird brain deal witha bird’s eye view? I’m curious – and I still am, because so far I have not found a lot of research on the topic. Indeed, I imagine it’s difficult to come up with a definitive way to determine what a bird is experiencing for the sake of a laboratory experiment. Although, if I had to hazard a guess, perhaps much of a bird’s reaction to what it sees relies on more primitive structures – maybe birds rely more on instinct than interpretation? While this seems to remain mysterious, scientists do know some neat stuff about how birds’ eyes function in ways that allow them to see what we can’t. Check it out!
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Telepathic rats communicate via brain-to-brain connections
Scientists from Duke University and Brazil claim wires connecting one rodent to another can allow communication spanning continents via the internet. Professor Miguel Nicolelis of Duke University in Durham, North Carolina, led a team of researchers who demonstrated that it is possible to transmit instructions from one animal to another by brain-to-brain communication, a process akin to telepathy.
Brain-to-brain communication could be the start of organic-based computing based on networks of interconnected brains. Pairs of laboratory rats were able to communicate with each other using microscopic electrodes implanted into their brains. This occurred as part of an experiment where the two rats had to work together in order to receive a reward (see video at source).
Are you flushing away brain cells? How urine cells can give rise to neurons
Uh-oh, urine trouble! Well, now that that’s out of my system (ahem), how would you feel if you learned that you’ve been flushing away potential brain cells? I’m not talking about the copious amount of hours you’ve logged online or kicked back in front of the television just this past month. On a daily basis, you’re expelling 1-2 liters of a possible source of neurons in a way you’ve never expected – through urinating.
Back in 2009, stem-cell biologist Duanqing Pei demonstrated that kidney epithelial cells, a common component of urine, could be converted into induced pluripotent stem (iPS) cells, which have the ability to differentiate into any cell type found in the body. Recently, Pei and his colleagues at China’s Guangzhou Institutes of Biomedicine and Health took this technique a step further by converting iPS cells into functioning neurons. More
A Blacked Out Memory
Social gatherings are often the scene of hippocampal disruptions. (Scene from the movie Twelve)
“White Mike and his father moved after his mother died of breast cancer. It ate her up and most of their money. They can’t control the old radiators and its very hot in the spring time. In White Mike’s room, old unpacked boxes stick out of the closet so he can see them. Maybe you know how it is, maybe you don’t? But sometimes if you can’t see what you’re finished with its better. White Mike stripped to his shorts and laid down on the floor so he felt a little cooler. That’s how it was the first night in his new room and that’s how it still is. White Mike is thin and pale like smoke. White Mike has never smoked a cigarette in his life, never had a drink, never sucked down a doobie. He once went three days without sleep as a kind of experiment. That’s as close as he’s ever gotten to fucked up. White Mike has become a very good drug dealer.
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