Posts tagged neuroscience
Articles and news from the latest research reports.
Long-term memory in the cortex
Game changing results: Brain uses the cortex for making sensory associations, not the hippocampus
‘Where’ and ‘how’ memories are encoded in a nervous system is one of the most challenging questions in biological research. The formation and recall of associative memories is essential for an independent life. The hippocampus has long been considered a centre in the brain for the long-term storage of spatial associations. Now, Mazahir T. Hasan at the Max Planck Institute for Medical Research and José Maria Delgado-Garcìa at the University Pablo de Olavide of Seville, Spain, were able to provide first experimental evidence that a specific form of memory associations is encoded in the cerebral cortex and is not localized in the hippocampus as described in most Neuroscience textbooks. The new study is a game changer since it strongly suggests that the motor cortical circuits itself, and not the hippocampus, is used as memory storage.
Henry Molaison, known widely as H.M., is a famous name in memory research. Large parts of the American‘s hippocampus – the region of the brain that is a major element in learning and memory processes – were removed in the 1950s in an attempt to cure his epileptic seizures. He subsequently suffered severe memory lapses and was no longer able to remember virtually anything new he had learned. Most scientists thereby concluded that the hippocampus is the site of long-term memory.
However, the extent of H.M.’s brain damage was obviously underestimated, because other regions in addition to the hippocampus were also removed or damaged in the surgical procedure. The researchers from Heidelberg and Seville have therefore investigated the learning behaviour of genetically modified mice in which NMDA receptors are turned off only in the motor cerebral cortex. NMDA receptors bind the neurotransmitter glutamate to the synapses and become active when several signals feed into one synapse at the same time. They are the central molecular elements of learning processes, being involved in increasing or decreasing transmission of the signals to synapses.
As the new study shows, in the motor cortex this so-called synaptic plasticity no longer functions without the NMDA receptors. The scientists were thus able to rule out the hippocampus or other regions as the cause for their observations. Based on the new findings, it is the cerebral cortex, not the hippocampus that is the storage site for some forms of memory.
In behaviour tests, so called eyeblink conditioning, animals with and without NMDA receptors in the primary motor cortex had to learn to link a tone with a subsequent electrical stimulus of the eyelid. This association of two sensory inputs involves the cerebellum which coordinates the necessary movements, as well as the hippocampus and the cerebral cortex, which are important learning and memory centres. “After a learning phase, the animals’ reflex is to close their eye when they hear just the tone. Without NMDA receptors in the primary motor cerebral cortex, the genetically modified mice on the other hand cannot remember the connection between the tone and electrical stimulus, and therefore they keep their eyes open despite the tone”, explains Mazahir T. Hasan of the Max Planck Institute for Medical Research.
The researchers have thus complemented the findings of their Heidelberg-based colleagues that the hippocampus is not the seat of memory. In July 2012, Rolf Sprengel and Peter Seeburg from the Max Planck Institute for Medical Research discovered that mice without NMDA receptors in the hippocampus are still quite capable of learning. “We now think that the hippocampus provides the necessary environmental cues, which are transmitted to the cortex where learning-dependent associations take place. Memories are thus stored at various sites in the cerebral cortex on a long-term basis”, explains Hasan.
The findings of Hasan and Delgado-Garcìa thus represent a paradigm-shift in memory research as they make clear that the cerebral cortex is the brain region where memory associations are linked and stored – not the hippocampus. An advanced and detailed knowledge of the mechanisms for the acquisition, consolidation, and recall of associations in the brain is the prerequisite for a therapeutic treatment of the devastating effects of memory loss in various neurological diseases, such as amnesia, Alzheimer`s disease and dementia.
Drug blocks light sensors in eye that may trigger migraine attacks
New compound by Salk scientists offers a way to treat migraine and potentially other disorders of the central nervous system
For many migraine sufferers, bright lights are a surefire way to exacerbate their headaches. And for some night-shift workers, just a stroll through a brightly lit parking lot during the morning commute home can be enough to throw off their body’s daily rhythms and make daytime sleep nearly impossible. But a new molecule that selectively blocks specialized light-sensitive receptors in the eyes could help both these groups of people, without affecting normal vision according to a study published August 25, 2013 in Nature Chemical Biology.
"It took almost ten years to find and test a molecule that fit all the properties and acted in vivo as we wanted," says senior study author Satchidananda Panda, an associate professor in Salk’s Regulatory Biology Laboratory.
Scientists have known for nearly a century that humans and animals can sense light even when they can’t see. Before they’ve opened their eyes, and even before cells that allow vision have matured, newborn mice still scurry away from bright lights, and set their sleep-wake cycles based on the patterns of light and dark throughout the day. The same is true of many blind people-though they can’t see what’s in front of them, their bodies still follow daily circadian rhythms, and the pupils of their eyes constrict in response to light.
More than ten years ago, Panda’s lab group discovered that melanopsin, a receptor found in neurons connecting the eyes and brain, is responsible for sensing light independently of normal vision. Since then, researchers have determined that the receptor is vital for maintaining sleep cycles and other circadian rhythms in those with healthy vision, constricting the pupil of the eye in bright light, and potentially exacerbating the light-sensitivity associated with migraine headaches. While melanopsin senses light for these non-vision purposes in the body, closely related receptors-rhodopsin and cone opsins-provide vision-forming information to the brain.
Panda figured that if he could find a compound that blocked melanopsin, but not rhodopsin or cone opsins, it could pave the way toward treating migraines or circadian rhythm imbalances. Scientists already know of one class of compounds, retinoids, which interact with opsins, but they’re non-specific and so bind to melanopsin, rhodopsin, cone opsins, and a whole handful of other receptors in the body, causing widespread side effects. Panda wanted something more specific. So for ten years, his lab group, in collaboration with scientists at the pharmaceutical company Lundbeck, has attempted to find chemical compounds that specifically shut off melanopsin in animals.
In their latest search, Panda and his collaborators turned to the Lundbeck library of diverse compounds. In hundreds of 384-well plates, a team led by Ken Jones at Lundbeck tested whether each chemical from the library turned off melanopsin by measuring the calcium levels after the plate was exposed to light. When melanopsin is functioning, calcium levels increase after light exposure indicating that light has been sensed and a signal is being generated. Several compounds from the chemical library stopped this calcium increase from happening, suggesting that they were blocking the function of melanopsin.
None of these compounds looked like retinoids, so it was an exciting breakthrough, Panda says. The chemicals, dubbed opsinamides, also showed no interaction with rhodopsin or other opsins. “We wanted to make sure they were specific to melanopsin,” says Panda. To find out whether the opsinamides would have a physiological response in addition to binding to melanopsin in bench experiments, Megumi Hatori and Ludovic Mure from Panda’s Salk lab group next looked at whether the drug affected the pupillary constriction in mice. Normally, in extremely bright light, the pupil of the eye shrinks to its smallest size. But when the mice were treated with one of the opsinamides, their pupils didn’t shrink as usual. Most importantly, the drug had no detectable effect in mice lacking melanopsin, further showing its specificity for melanopsin. Finally, newborn mice treated with the compound no longer avoided bright lights. The results, Panda says, show that the drug is stopping melanopsin from signaling the brain when the eyes are exposed to bright light.
"So far, everything known about melanopsin has been discovered using knock-out mice that completely lack the receptor," says Panda. "So this offers a new way to study the protein." Kenneth Jones, the former project head at Lundbeck, notes that "the two compounds require further optimization in anticipation of clinical testing but are extraordinarily useful for research purposes and as leads in the discovery process." Co-author Jeffrey Sprouse has co-founded a start-up company, Cyanaptic, to do just that.
Once more effective compounds are developed, Panda expects that they could eventually have utility in a variety of clinical settings. “There are many people who would like to work when they have migraine pain exacerbated by light,” he says. “If these drugs could stop the light-sensitivity associated with the headaches, it would enable them to be much more productive.”
Moreover, Panda says, the drugs could help shift-workers set their sleep schedules without exposure to sunlight interfering with their circadian rhythms. His lab group doesn’t yet have results on how the drugs affect circadian rhythms, but based on the known mechanisms of melanopsin, Panda says that it is likely the new opsinamides alter sleep.
Researchers Find Promising Therapeutic Target for Hard-To-Treat Brain Tumor
Specific protein found in nearly all high-grade meningiomas
Johns Hopkins researchers say they have found a specific protein in nearly 100 percent of high-grade meningiomas — the most common form of brain tumor — suggesting a new target for therapies for a cancer that does not respond to current chemotherapy.
Importantly, the investigators say, the protein — NY-ESO-1 — is already at the center of a clinical trial underway at the National Cancer Institute. That trial is designed to activate the immune systems of patients with other types of tumors that express the protein, training the body to attack the cancer and eradicate it.
“Typically there is a lag time before a laboratory finding like this leads to a clear path forward to help patients. But in this case, since there is already a clinical trial underway, we have a chance of helping people sooner rather than later,” says Gregory J. Riggins, M.D., Ph.D., a professor of neurosurgery at the Johns Hopkins University School of Medicine and the senior author of the study published online in the journal Cancer Immunology Research.
In the NCI trial, NY-ESO-1 is found in a much smaller percentage of tumors than Riggins and his team found in high-grade meningioma, suggesting that for the brain cancer, the target would be potentially more significant.
Most low-grade meningiomas located in easy-to-reach locations can be treated successfully with surgery and radiation. But more atypical, higher-grade tumors are much more difficult to eradicate and are deadlier.
Riggins and his colleagues, including Gilson S. Baia, Ph.D., and Otavia L. Caballero, M.D., Ph.D., set out to find cancer antigens in meningioma. Cancer antigens are proteins expressed in tumors but not in healthy cells, making them good targets for chemical or immune system attack. They looked specifically at 37 cancer/testis (CT) genes, which are not found in normal cells in the body except in germ cells and cells cordoned off in the testicles or, in some cases, ovaries.
CT genes are activated, however, in various cancers. While they are seen as “foreign” by the body’s immune system, they are often locked behind the sophisticated defense system that cancers use to evade attack by immune cells. Finding a way to get the immune system to see these protein antigens, however, could allow for the body to recognize the invasion and go after the cancer cells. Various approaches are being used to do that, including vaccines and a system involving removing T-cells from the body and reprogramming them before returning them and setting them loose on the cancer cells.
The Johns Hopkins researchers took tissue from 18 different meningioma samples, removed the genetic material and protein and checked at what levels the 37 different genes were turned on. The gene that is the blueprint for the NY-ESO-1 protein was turned on more frequently than any other, in five of the 18 patient samples.
Then they analyzed NY-ESO-1 expression in a larger group of 110 meningioma tissue samples. They found NY-ESO-1 in 108 of them. The more expression in the sample, they also determined, the higher the tumor grade. The higher levels of NY-ESO-1 expressed also correlated with significantly lower disease-free and overall survival rates in the patients they came from.
The NCI trial originally began in melanoma patients. NY-ESO-1 is expressed in roughly one-third of melanomas as well as approximately one-third of breast, prostate, lung, ovarian, thyroid and bladder cancers, as well as sarcomas. Riggins and his team did not find the protein in glioblastoma, the deadliest form of brain cancer.
He calls the fact that the NCI trial could now include meningioma patients a “stroke of luck.”
“If that therapy did not exist, there would be a lot of work that would have to be done to convince people to pursue this,” Riggins says. “Our goal is to get something that works to the patients. This puts us well on our way.”
(Source: hopkinsmedicine.org)
Researcher controls colleague’s motions in 1st human brain-to-brain interface
University of Washington researchers have performed what they believe is the first noninvasive human-to-human brain interface, with one researcher able to send a brain signal via the Internet to control the hand motions of a fellow researcher.
Using electrical brain recordings and a form of magnetic stimulation, Rajesh Rao sent a brain signal to Andrea Stocco on the other side of the UW campus, causing Stocco’s finger to move on a keyboard.
While researchers at Duke University have demonstrated brain-to-brain communication between two rats, and Harvard researchers have demonstrated it between a human and a rat, Rao and Stocco believe this is the first demonstration of human-to-human brain interfacing.
“The Internet was a way to connect computers, and now it can be a way to connect brains,” Stocco said. “We want to take the knowledge of a brain and transmit it directly from brain to brain.”
The researchers captured the full demonstration on video recorded in both labs.
Rao, a UW professor of computer science and engineering, has been working on brain-computer interfacing in his lab for more than 10 years and just published a textbook on the subject. In 2011, spurred by the rapid advances in technology, he believed he could demonstrate the concept of human brain-to-brain interfacing. So he partnered with Stocco, a UW research assistant professor in psychology at the UW’s Institute for Learning & Brain Sciences.
On Aug. 12, Rao sat in his lab wearing a cap with electrodes hooked up to an electroencephalography machine, which reads electrical activity in the brain. Stocco was in his lab across campus wearing a purple swim cap marked with the stimulation site for the transcranial magnetic stimulation coil that was placed directly over his left motor cortex, which controls hand movement.
The team had a Skype connection set up so the two labs could coordinate, though neither Rao nor Stocco could see the Skype screens.
Rao looked at a computer screen and played a simple video game with his mind. When he was supposed to fire a cannon at a target, he imagined moving his right hand (being careful not to actually move his hand), causing a cursor to hit the “fire” button. Almost instantaneously, Stocco, who wore noise-canceling earbuds and wasn’t looking at a computer screen, involuntarily moved his right index finger to push the space bar on the keyboard in front of him, as if firing the cannon. Stocco compared the feeling of his hand moving involuntarily to that of a nervous tic.
“It was both exciting and eerie to watch an imagined action from my brain get translated into actual action by another brain,” Rao said. “This was basically a one-way flow of information from my brain to his. The next step is having a more equitable two-way conversation directly between the two brains.”
The technologies used by the researchers for recording and stimulating the brain are both well-known. Electroencephalography, or EEG, is routinely used by clinicians and researchers to record brain activity noninvasively from the scalp. Transcranial magnetic stimulation is a noninvasive way of delivering stimulation to the brain to elicit a response. Its effect depends on where the coil is placed; in this case, it was placed directly over the brain region that controls a person’s right hand. By activating these neurons, the stimulation convinced the brain that it needed to move the right hand.
Computer science and engineering undergraduates Matthew Bryan, Bryan Djunaedi, Joseph Wu and Alex Dadgar, along with bioengineering graduate student Dev Sarma, wrote the computer code for the project, translating Rao’s brain signals into a command for Stocco’s brain.
“Brain-computer interface is something people have been talking about for a long, long time,” said Chantel Prat, assistant professor in psychology at the UW’s Institute for Learning & Brain Sciences, and Stocco’s wife and research partner who helped conduct the experiment. “We plugged a brain into the most complex computer anyone has ever studied, and that is another brain.”
At first blush, this breakthrough brings to mind all kinds of science fiction scenarios. Stocco jokingly referred to it as a “Vulcan mind meld.” But Rao cautioned this technology only reads certain kinds of simple brain signals, not a person’s thoughts. And it doesn’t give anyone the ability to control your actions against your will.
Both researchers were in the lab wearing highly specialized equipment and under ideal conditions. They also had to obtain and follow a stringent set of international human-subject testing rules to conduct the demonstration.
“I think some people will be unnerved by this because they will overestimate the technology,” Prat said. “There’s no possible way the technology that we have could be used on a person unknowingly or without their willing participation.”
Stocco said years from now the technology could be used, for example, by someone on the ground to help a flight attendant or passenger land an airplane if the pilot becomes incapacitated. Or a person with disabilities could communicate his or her wish, say, for food or water. The brain signals from one person to another would work even if they didn’t speak the same language.
Rao and Stocco next plan to conduct an experiment that would transmit more complex information from one brain to the other. If that works, they then will conduct the experiment on a larger pool of subjects.
Not guility: Parkinson and protein phosphorylation
EPFL scientists exonerated a process thought to play a role in causing Parkinson’s disease; rather than triggering toxic aggregates in neurons, it turns out that it actually slows down the disease, pharmas have now new tracks to explore
Clues left at the scene of the crime don’t always point to the guilty party, as EPFL researchers investigating Parkinson’s disease have discovered. It is generally accepted that the disease is aggravated when a specific protein is transformed by an enzyme. The EPFL neuroscientists were able to show that, on the contrary, this transformation tends to protect against the progression of the disease. This surprising conclusion could radically change therapeutic approaches that are currently being developed by pharmaceutical companies. The research is to appear in an article in the Proceedings of the National Academy of Sciences (PNAS).
Parkinson’s disease is characterized by the accumulation of a protein known as alpha-synuclein in the brain. If too much of it is produced or if it’s not eliminated properly, it then aggregates into small clumps inside the neurons, eventually killing them. Several years ago scientists discovered that these aggregated proteins in the brain had undergone a transformation known as “phosphorylation” — a process in which an enzyme adds an extra chemical element to a protein, thus modifying its properties.
The investigators’ conclusion that the enzyme’s activity could be responsible for the disease seems eminently reasonable. If phosphorylation and protein aggregation go hand in hand, then it makes sense that one should cause the other. This is the assumption that researchers and pharmaceutical companies made as they tried to reduce the phosphorylation by deactivating an enzyme involved in the process. But they have been following a false lead, as the EPFL team was able to show.
The scientists even discovered that the phosphorylation of the protein has positive effects. On the one hand, it considerably reduces the toxic aggregation of the protein, and on the other, it helps the cell eliminate the protein. “The two phenomena are undoubtedly related, and together could play a role in the reduction of alpha-synuclein toxicity, but we don’t yet understand the impact of both processes at each stage of the disease,” explains neurobiologist Abid Oueslati, first author on the study.
Going back to the beginning
To reach this conclusion, the biologists had to explore the initial disease conditions. They injected into rat neurons what were thought to be the elements needed to trigger the disease: an overexpression of alpha-synuclein and the enzyme that phosphorylates it (PLK2).
To their surprise, the group of animals subjected to both of the parameters — overproduction of the protein and phosphorylation — lost nearly 70% fewer neurons than another group in which only the protein was overexpressed. Consequently, they had fewer lesions, and less Parkinson symptoms.
"We owe this discovery to unique tools that we developed, in collaboration with the Aebischer group, in order to study the effect of this transformation at the molecular level. ," explains Hilal Lashuel, who directed the study. Our study revealed the limitations of the most commonly used approach, which uses genetic mutations to mimic this process.
Lashuel thinks it is highly probable that the phosphorylation of the proteins takes place after they are aggregated, that is to say once the disease is already established. Or it could be a defense mechanism of the neurons, an attempt to try and slow down the progression of the disease from the beginning.
The scientists’ research opens doors for the development of future drug therapies. “The lesson we learned from this research is that everything you find at the scene of a crime is not necessarily involved in the crime. By remaining fixated on that assumption, we may lose sight of the bigger picture.”
(Source: eurekalert.org)
Touch and Movement Neurons Shape the Brain’s Internal Image of the Body
The brain’s tactile and motor neurons, which perceive touch and control movement, may also respond to visual cues, according to researchers at Duke Medicine.
The study in monkeys, which appears online Aug. 26, 2013, in the journal Proceedings of the National Academy of Sciences, provides new information on how different areas of the brain may work together in continuously shaping the brain’s internal image of the body, also known as the body schema.
The findings have implications for paralyzed individuals using neuroprosthetic limbs, since they suggest that the brain may assimilate neuroprostheses as part of the patient’s own body image.
“The study shows for the first time that the somatosensory or touch cortex may be influenced by vision, which goes against everything written in neuroscience textbooks,” said senior author Miguel Nicolelis, M.D., PhD, professor of neurobiology at Duke University School of Medicine. “The findings support our theory that the cortex isn’t strictly segregated into areas dealing with one function alone, like touch or vision.”
Earlier research has shown that the brain has an internal spatial image of the body, which is continuously updated based on touch, pain, temperature and pressure – known as the somatosensory system – received from skin, joints and muscles, as well as from visual and auditory signals.
An example of this dynamic process is the “rubber hand illusion,” a phenomenon in which people develop a sense of ownership of a fake hand when they view it being touched at the same time that something touches their own hand.
In an effort to find a physiological explanation for the “rubber hand illusion,” Duke researchers focused on brain activity in the somatosensory and motor cortices of monkeys. These two areas of the brain do not directly receive visual input, but previous work in rats, conducted at the Edmond and Lily Safra International Institute of Neuroscience of Natal in Brazil, theorized that the somatosensory cortex could respond to visual cues.
In the Duke experiment, the two monkeys observed a realistic, computer-generated image of a monkey arm on a screen being touched by a virtual ball. At the same time, the monkeys’ arms were touched, triggering a response in their somatosensory and motor cortical areas.
The monkeys then observed the ball touching the virtual arm without anything physically touching their own arms. Within a matter of minutes, the researchers saw the neurons located in the somatosensory and motor cortical areas begin to respond to the virtual arm alone being touched.
The responses to virtual touch occurred 50 to 70 milliseconds later than physical touch, which is consistent with the timing involved in the pathways linking the areas of the brain responsible for processing visual input to the somatosensory and motor cortices. Demonstrating that somatosensory and motor cortical neurons can respond to visual stimuli suggests that cross-functional processing occurs throughout the primate cortex through a highly distributed and dynamic process.
“These findings support our notion that the brain works like a grid or network that is continuously interacting,” Nicolelis said. “The cortical areas of the brain are processing multiple streams of information at the same time instead of being segregated as we previously thought.”
The research has implications for the future design of neuroprosthetic devices controlled by brain-machine interfaces, which hold promise for restoring motor and somatosensory function to millions of people who suffer from severe levels of body paralysis. Creating neuroprostheses that become fully incorporated in the brain’s sensory and motor circuitry could allow the devices to be integrated into the brain’s internal image of the body. Nicolelis said he is incorporating the findings into the Walk Again Project, an international collaboration working to build a brain-controlled neuroprosthetic device. The Walk Again Project plans to demonstrate its first brain-controlled exoskeleton during the opening ceremony of the 2014 FIFA Football World Cup.
“As we become proficient in using tools – a violin, tennis racquet, computer mouse, or prosthetic limb – our brain is likely changing its internal image of our bodies to incorporate the tools as extensions of ourselves,” Nicolelis said.
(Image: Getty images)
Language can reveal the invisible
It is natural to imagine that the sense of sight takes in the world as it is — simply passing on what the eyes collect from light reflected by the objects around us.
But the eyes do not work alone. What we see is a function not only of incoming visual information, but also how that information is interpreted in light of other visual experiences, and may even be influenced by language.
Words can play a powerful role in what we see, according to a study published this month by UW-Madison cognitive scientist and psychology professor Gary Lupyan, and Emily Ward, a Yale University graduate student, in the journal Proceedings of the National Academy of Sciences.
"Perceptual systems do the best they can with inherently ambiguous inputs by putting them in context of what we know, what we expect," Lupyan says. "Studies like this are helping us show that language is a powerful tool for shaping perceptual systems, acting as a top-down signal to perceptual processes. In the case of vision, what we consciously perceive seems to be deeply shaped by our knowledge and expectations."
And those expectations can be altered with a single word.
To show how deeply words can influence perception, Lupyan and Ward used a technique called continuous flash suppression to render a series of objects invisible for a group of volunteers.
Each person was shown a picture of a familiar object — such as a chair, a pumpkin or a kangaroo — in one eye. At the same time, their other eye saw a series of flashing, “squiggly” lines.
"Essentially, it’s visual noise," Lupyan says. "Because the noise patterns are high-contrast and constantly moving, they dominate, and the input from the other eye is suppressed."
Immediately before looking at the combination of the flashing lines and suppressed object, the study participants heard one of three things: the word for the suppressed object (“pumpkin,” when the object was a pumpkin), the word for a different object (“kangaroo,” when the object was actually a pumpkin), or just static.
Then researchers asked the participants to indicate whether they saw something or not. When the word they heard matched the object that was being wiped out by the visual noise, the subjects were more likely to report that they did indeed see something than in cases where the wrong word or no word at all was paired with the image.
"Hearing the word for the object that was being suppressed boosted that object into their vision," Lupyan says.
And hearing an unmatched word actually hurt study subjects’ chances of seeing an object.
"With the label, you’re expecting pumpkin-shaped things," Lupyan says. "When you get a visual input consistent with that expectation, it boosts it into perception. When you get an incorrect label, it further suppresses that."
Experiments have shown that continuous flash suppression interrupts sight so thoroughly that there are no signals in the brain to suggest the invisible objects are perceived, even implicitly.
"Unless they can tell us they saw it, there’s nothing to suggest the brain was taking it in at all," Lupyan says. "If language affects performance on a test like this, it indicates that language is influencing vision at a pretty early stage. It’s getting really deep into the visual system."
The study demonstrates a deeper connection between language and simple sensory perception than previously thought, and one that makes Lupyan wonder about the extent of language’s power. The influence of language may extend to other senses as well.
"A lot of previous work has focused on vision, and we have neglected to examine the role of knowledge and expectations on other modalities, especially smell and taste," Lupyan says. "What I want to see is whether we can really alter threshold abilities," he says. "Does expecting a particular taste for example, allow you to detect a substance at a lower concentration?"
If you’re drinking a glass of milk, but thinking about orange juice, he says, that may change the way you experience the milk.
"There’s no point in figuring out what some objective taste is," Lupyan says. "What’s important is whether the milk is spoiled or not. If you expect it to be orange juice, and it tastes like orange juice, it’s fine. But if you expected it to be milk, you’d think something was wrong."
(Source: news.wisc.edu)
Combination of Two Imaging Techniques Allows New Insights into Brain Function
The ability to measure brain functions non-invasively is important both
for clinical diagnoses and research in Neurology and Psychology. Two main imaging techniques are used: positron emission tomography (PET), which reveals metabolic processes in the brain; and activity of different brain regions is measured on the basis of the cells’ oxygen consumption by magnetic resonance imaging (MRI). A direct comparison of PET and MRI measurements was previously difficult because each had to be performed in a separate machine.
Researchers from the Werner Siemens Imaging Center at the University of Tübingen under the direction of Professor Bernd J. Pichler in collaboration with the Department of Diagnostic and Interventional Radiology, University Hospital Tübingen, and the Tübingen Max Planck Institute for Intelligent Systems have now successfully combined both methods. The researchers are able to explore functional processes in the brain in detail and can better assess what course of action to take. These results were achieved by the use of a PET insert enabling complementary, simultaneous PET/MRI scans. It was developed and built at the University of Tübingen.
The researchers could identify in certain regions a mismatch between glucose metabolism related brain activation measured with PET and oxygenation related signals, measured with MRI. Furthermore information about functional connectivity in the brain could be derived from MRI and from dynamic PET data. These results help to further decipher the nature of brain function, and are ultimately useful for basic research as well as clinical practice. The study, by lead author Dr. Hans Wehrl of Professor Bernd J. Pichler’s research team is soon to be published in the journal “Nature Medicine”.
In PET imaging the distribution of a weakly radioactive substance is shown in cross sections of the body, enabling doctors to see many different metabolic and physiological functions at work. Functional MRI (fMRI) allows researchers to depict changes in blood oxygenation that are associated with brain function. This measurement of functional active brain regions is also important for the planning of brain surgeries, where particular care must be taken in certain areas. The ability to collect different kinds of data from different scans simultaneously represents a major step forward in the fields using these technologies.
(Source: alphagalileo.org)
Researchers discover how inhibitory neurons behave during critical periods of learning
We’ve all heard the saying “you can’t teach an old dog new tricks.” Now neuroscientists are beginning to explain the science behind the adage.
For years, neuroscientists have struggled to understand how the microcircuitry of the brain makes learning easier for the young, and more difficult for the old. New findings published in the journal Nature by Carnegie Mellon University, the University of California, Los Angeles and the University of California, Irvine show how one component of the brain’s circuitry — inhibitory neurons — behave during critical periods of learning.
The brain is made up of two types of cells — inhibitory and excitatory neurons. Networks of these two kinds of neurons are responsible for processing sensory information like images, sounds and smells, and for cognitive functioning. About 80 percent of neurons are excitatory. Traditional scientific tools only allowed scientists to study the excitatory neurons.
"We knew from previous studies that excitatory cells propagate information. We also knew that inhibitory neurons played a critical role in setting up heightened plasticity in the young, but ideas about what exactly those cells were doing were controversial. Since we couldn’t study the cells, we could only hypothesize how they were behaving during critical learning periods," said Sandra J. Kuhlman, assistant professor of biological sciences at Carnegie Mellon and member of the joint Carnegie Mellon/University of Pittsburgh Center for the Neural Basis of Cognition.
The prevailing theory on inhibitory neurons was that, as they mature, they reach an increased level of activity that fosters optimal periods of learning. But as the brain ages into adulthood and the inhibitory neurons continue to mature, they become even stronger to the point where they impede learning.
Newly developed genetic and imaging technologies are now allowing researchers to visualize inhibitory neurons in the brain and record their activity in response to a variety of stimuli. As a postdoctoral student at UCLA in the laboratory of Associate Professor of Neurobiology Joshua T. Trachtenberg, Kuhlman and her colleagues used these new techniques to record the activity of inhibitory neurons during critical learning periods. They found that, during heightened periods of learning, the inhibitory neurons didn’t fire more as had been expected. They fired much less frequently — up to half as often.
"When you’re young you haven’t experienced much, so your brain needs to be a sponge that soaks up all types of information. It seems that the brain turns off the inhibitory cells in order to allow this to happen," Kuhlman said. "As adults we’ve already learned a great number of things, so our brains don’t necessarily need to soak up every piece of information. This doesn’t mean that adults can’t learn, it just means when they learn, their neurons need to behave differently."
Study in mice links cocaine use to new brain structures
Mice given cocaine showed rapid growth in new brain structures associated with learning and memory, according to a research team from the Ernest Gallo Clinic and Research Center at UC San Francisco. The findings suggest a way in which drug use may lead to drug-seeking behavior that fosters continued drug use, according to the scientists.
The researchers used a microscope that allowed them to peer directly into nerve cells within the brains of living mice, and within two hours of giving a drug they found significant increases in the density of dendritic spines – structures that bear synapses required for signaling – in the animals’ frontal cortex. In contrast, mice given saline solution showed no such increase.
The researchers also found a relationship between the growth of new dendritic spines and drug-associated learning. Specifically, mice that grew the most new spines were those that developed the strongest preference for being in the enclosure where they received cocaine rather than in the enclosure where they received saline. The team published its findings online in Nature Neuroscience on August 25, 2013.
"This gives us a possible mechanism for how drug use fuels further drug-seeking behavior," said principal investigator Linda Wilbrecht, PhD, a Gallo investigator now at UC Berkeley, but who led the research while she was on the UCSF faculty.
"It’s been observed that long-term drug users show decreased function in the frontal cortex in connection with mundane cues or tasks, and increased function in response to drug-related activity or information," Wilbrecht said. "This research suggests how the brains of drug users might shift toward those drug-related associations."
In all living brains there is a baseline level of creation of new spines in response to, or in anticipation of, day-to-day learning, Wilbrecht said. By enhancing this growth, cocaine might be a super-learning stimulus that reinforces learning about the cocaine experience, she said.
The frontal cortex, which Wilbrecht called the “steering wheel” of the brain, controls functions such as long-term planning, decision-making and other behaviors involving higher reasoning and discipline.
The brain cells in the frontal cortex that Wilbrecht and her team studied regulate the output of this brain region, and may play a key role in decision-making. “These neurons, which are directly affected by cocaine use, have the potential to bias decision-making,” she said.
Wilbrecht said the findings could potentially advance research in human addiction “by helping us identify what is going awry in the frontal cortexes of drug-addicted humans, and by explaining how drug-related cues come to dominate the brain’s decision-making processes.”
In the first of a series of experiments, the scientists gave cocaine injections to one group of mice and saline injections to another. The next day, they observed the animals’ brain cells using a 2-photon laser scanning microscope. They were surprised to discover that even after the first dose, the mice treated with cocaine grew more new dendritic spines than the saline-treated mice.
In another experiment, they observed the mice before cocaine or saline treatment and then two hours afterward, and discovered that the animals that received cocaine were developing new dendritic spines within two hours after receiving the drug. Furthermore, the next morning, cocaine-induced spines accounted for almost four times more connections among nerve cells than was observed in saline-treated animals.
In a third experiment, the researchers for a week gave the mice cocaine in one distinctive chamber and saline in another, using identical procedures. Each chamber had its own characteristic visual design, texture and smell to distinguish it from the other chamber. They then let the mice choose which chamber to go to.
"The animals that showed the highest quantity of robust dendritic spines – the spines with the greatest likelihood of developing into synapses – showed the greatest change in preference toward the chamber where they received the cocaine," said Wilbrecht. "This suggests that the new spines might be material for the association that these mice have learned to make between the chamber and the drug."
Wilbrecht noted that the research would not have been possible without live brain imaging via the 2-photon laser scanning microscope, which was developed in 2002. “I grew up at the time of the famous public service campaign that showed a pan of frying eggs with the message, ‘this is your brain on drugs,’” recalled Wilbrecht. “Now, with this microscope, we can actually say, ‘this is a brain cell on drugs.’”
(Source: eurekalert.org)