Posts tagged neuroscience
Articles and news from the latest research reports.
The Bitter and the Sweet: Fruit Flies Reveal a New Interaction Between the Two
Fruit flies have a lot to teach us about the complexity of food. Like these tiny little creatures, most animals are attracted to sugar but are deterred from eating it when bitter compounds are added.
A new study conducted by UC Santa Barbara’s Craig Montell, Duggan Professor of Neuroscience in the Department of Molecular, Cellular and Developmental Biology, explains a breakthrough in understanding how sensory input impacts fruit flies’ decisions about sweet taste. The findings were published today in the journal Neuron.
It is generally well known that the addition of bitter compounds inhibits attraction to sugars. However, until now the cellular and molecular mechanisms underlying an important aspect of this ubiquitous animal behavior were poorly understood.
When animals encounter bitterness in foods, two factors cause them to stop eating. First, bitter compounds bind to proteins called bitter gustatory receptors (GRs), which inhibits feeding. The second –– and more elusive –– factor involves inhibition of the sugar response. This is the focus of Montell’s research.
At the center of the team’s discovery is the function of an odorant-binding protein (OPB) in the gustatory system. These proteins are usually but not exclusively resident in the olfactory system. Montell’s team found definitive evidence that an OBP, synthesized and released from non-neuronal cells, not only binds bitter tastants, but also moves and binds to the surface of nearby gustatory receptor neurons (GRNs) that contain sugar-activated GRs.
This unanticipated process inhibits the activity of these GRNs and reduces the fruit flies’ attraction to sugars. These results not only reveal an unexpected role for an OBP in taste, but also identify the first molecular player (OBP49a) involved in the integration of opposing attractive and aversive gustatory stimuli in fruit flies.
The researchers used two different fruit flies, wild-type and mutants missing the OBP49a protein, to demonstrate that bitter compounds suppress feeding behavior by binding to the OBP49a protein. As expected, wild-type flies find bitter aversive and prefer the lower concentration of sucrose when the higher concentration of sucrose is laced with bitter tastants such as quinine.
The same was not true of the mutant flies, which do not express OBP49a. Their avoidance behavior was impaired because the bitter compounds did not inhibit the sweet response by binding to OPB49. However, loss of OBP49a did not affect gustatory behavior or action potentials in sugar- or bitter-activated GRNs when the GRNs were presented with just one type of tastant.
"We showed that the OBP49a protein was in very close proximity or even touching the sugar GRs," said Montell. "If the bitter compound weren’t present, there would be normal sugar activation. We found that decreased behavioral avoidance to a sucrose/aversive mixture in the mutant flies was due to a deficit in the sugar-activated GRNs and not due to effects on GRNs activated by bitter compounds."
OBP49a is the first molecule shown to promote the inhibition of the sucrose-activated GRNs by aversive chemicals in fruit flies. The findings demonstrate at least one important cellular mechanism through which bitter and sweet taste integration occurs in the taste receptor neurons. However, the findings do not exclude the possibility that suppression of sweet by bitter compounds could also take place through the integration of separate bitter and sweet inputs in the brain.
"As we get a better understanding of aversive and attractive chemosensory behaviors in flies, it helps us understand how insect pests can be controlled," said Montell. "This is a step toward understanding the behaviors of related insects that spread disease. Molecules related to the OBPs and GRs in fruit flies are also in ticks and mosquitos that spread parasites and viruses."
Brain circuit can tune anxiety
New findings may help neuroscientists pinpoint better targets for antianxiety treatments.
Anxiety disorders, which include posttraumatic stress disorder, social phobias and obsessive-compulsive disorder, affect 40 million American adults in a given year. Currently available treatments, such as antianxiety drugs, are not always effective and have unwanted side effects.
To develop better treatments, a more specific understanding of the brain circuits that produce anxiety is necessary, says Kay Tye, an assistant professor of brain and cognitive sciences and member of MIT’s Picower Institute for Learning and Memory.
“The targets that current antianxiety drugs are acting on are very nonspecific. We don’t actually know what the targets are for modulating anxiety-related behavior,” Tye says.
In a step toward uncovering better targets, Tye and her colleagues have discovered a communication pathway between two brain structures — the amygdala and the ventral hippocampus — that appears to control anxiety levels. By turning the volume of this communication up and down in mice, the researchers were able to boost and reduce anxiety levels.
Lead authors of the paper, which appears in the Aug. 21 issue of Neuron, are technical assistant Ada Felix-Ortiz and postdoc Anna Beyeler. Other authors are former research assistant Changwoo Seo, summer student Christopher Leppla and research scientist Craig Wildes.
Measuring anxiety
Both the hippocampus, which is necessary for memory formation, and the amygdala, which is involved in memory and emotion processing, have previously been implicated in anxiety. However, it was unknown how the two interact.
To study those interactions, the researchers turned to optogenetics, which allows them to engineer neurons to turn their electrical activity on or off in response to light. For this study, the researchers modified a set of neurons in the basolateral amygdala (BLA); these neurons send long projections to cells of the ventral hippocampus.
The researchers tested the mice’s anxiety levels by measuring how much time they were willing to spend in a situation that normally makes them anxious. Mice are naturally anxious in open spaces where they are easy targets for predators, so when placed in such an area, they tend to stay near the edges.
When the researchers activated the connection between cells in the amygdala and the hippocampus, the mice spent more time at the edges of an enclosure, suggesting they felt anxious. When the researchers shut off this pathway, the mice became more adventurous and willing to explore open spaces. However, when these mice had this pathway turned back on, they scampered back to the security of the edges.
Complex interactions
In a study published in 2011, Tye found that activating a different subset of neurons in the amygdala had the opposite effect on anxiety as the neurons studied in the new paper, suggesting that anxiety can be modulated by many different converging inputs.
“Neurons that look virtually indistinguishable from each other in a single region can project to different regions and these different projections can have totally opposite effects on anxiety,” Tye says. “Anxiety is such an important trait for survival, so it makes sense that you want some redundancy in the system. You want a couple of different avenues to modulate anxiety.”
The Neuron study contributes significantly to scientists’ understanding of the roles of the amygdala and hippocampus in anxiety and offers directions for seeking new drug targets, says Joshua Gordon, an associate professor of psychiatry at Columbia University.
“The study specifies a particular connection in the brain as being important for anxiety. One could imagine, then, identifying components of the machinery of that connection — synaptic proteins or ion channels, for example — that are particularly important for amygdala-hippocampal connectivity. If such specific components could be identified, they would be potential targets for novel antianxiety drugs,” says Gordon, who was not part of the research team.
In future studies, the MIT team plans to investigate the effects of the amygdala on other targets in the hippocampus and the prefrontal cortex, which has also been implicated in anxiety. Deciphering these circuits could be an important step toward finding better drugs to help treat anxiety.
Mood is Influenced by Immune Cells Called to the Brain in Response to Stress
New research shows that in a dynamic mind-body interaction during the interpretation of prolonged stress, cells from the immune system are recruited to the brain and promote symptoms of anxiety.
The findings, in a mouse model, offer a new explanation of how stress can lead to mood disorders and identify a subset of immune cells, called monocytes, that could be targeted by drugs for treatment of mood disorders.
The Ohio State University research also reveals new ways of thinking about the cellular mechanisms behind the effects of stress, identifying two-way communication from the central nervous system to the periphery – the rest of the body – and back to the central nervous system that ultimately influences behavior.
Unlike an infection, trauma or other problems that attract immune cells to the site of trouble in the body, this recruitment of monocytes that can promote inflammation doesn’t damage the brain’s tissue – but it does lead to symptoms of anxiety.
The research showed that the brain under prolonged stress sends signals out to the bone marrow, calling up monocytes. The cells travel to specific regions of the brain and generate inflammation that causes anxiety-like behavior.
In experiments conducted in mice, the research showed that repeated stress exposure caused the highest concentration of monocytes migrating to the brain. The cells surrounded blood vessels and penetrated brain tissue in several areas linked to fear and anxiety, including the prefrontal cortex, amygdala and hippocampus, and their presence led to anxiety-like behavior in the mice.
“In the absence of tissue damage, we have cells migrating to the brain in response to the region of the brain that is activated by the stressor,” said John Sheridan, senior author of the study, professor of oral biology and associate director of Ohio State’s Institute for Behavioral Medicine Research (IBMR).
“In this case, the cells are recruited to the brain by signals generated by the animal’s interpretation of social defeat as stressful.”
The research appears in the Aug. 21, 2013, issue of The Journal of Neuroscience.
Mice in this study were subjected to stress that might resemble a person’s response to persistent life stressors. In this model of stress, male mice living together are given time to establish a hierarchy, and then an aggressive male is added to the group for two hours. This elicits a “fight or flight” response in the resident mice as they are repeatedly defeated. The experience of social defeat leads to submissive behaviors and the development of anxiety-like behavior.
Mice subjected to zero, one, three or six cycles of this social defeat were then tested for anxiety symptoms. The more cycles of social defeat, the higher the anxiety symptoms; mice took longer to enter an open space and opted for darkness rather than light when given the choice. Anxiety symptoms corresponded to higher levels of monocytes that had traveled to the animals’ brains from the blood.
Additional experiments showed that these cells did not originate in the brain, but traveled there from the bone marrow. In previous studies, this same research group showed that cells in the brain called microglia, the brain’s first line of immune defense, are activated by prolonged stress and are partly responsible for the signals that call up monocytes from the bone marrow.
“There are different moving parts from the central and peripheral components, and what’s novel is them coming together to influence behavior,” said Jonathan Godbout, a senior co-author of the paper and an associate professor of neuroscience at Ohio State.
Exactly what happens at this point in the brain remains unknown, but the research offers clues. The monocytes that travel to the brain don’t respond to natural anti-inflammatory steroids in the body and have characteristics signifying they are in a more inflammatory state. These results indicate that inflammatory gene expression occurs in the brain in response to the stressor.
“The monocytes are coming out of the bone marrow and they are not responsive to steroid regulation, so they overproduce proinflammatory signals when they’re stimulated. We think this is the key to the prolonged anxiety-like disorders that we see in these animals,” Sheridan said.
These findings do not apply to all forms of anxiety, the scientists noted, but they are a game-changer in research on stress-related mood disorders.
“Our data alter the idea of the neurobiology of mood disorders,” said Eric Wohleb, first author of the study and a predoctoral fellow in Ohio State’s Neuroscience Graduate Studies Program. “These findings indicate that a bidirectional system rather than traditional neurotransmitter pathways may regulate some forms of anxiety responses. We’re saying something outside the central nervous system – something from the immune system – is having a profound effect on behavior.”
(Source: newswise.com)
Schizophrenia symptoms linked to faulty ‘switch’ in brain
Scientists at The University of Nottingham have shown that psychotic symptoms experienced by people with schizophrenia could be caused by a faulty ‘switch’ within the brain.
In a study published today in the leading journal Neuron, they have demonstrated that the severity of symptoms such as delusions and hallucinations which are typical in patients with the psychiatric disorder is caused by a disconnection between two important regions in the brain — the insula and the lateral frontal cortex.
The breakthrough, say the academics, could form the basis for better, more targeted treatments for schizophrenia with fewer side effects.
The four-year study, led by Professor Peter Liddle and Dr Lena Palaniyappan in the University’s Division of Psychiatry and based in the Institute of Mental Health, centred on the insula region, a segregated ‘island’ buried deep within the brain, which is responsible for seamless switching between inner and outer world.
"Powerful explanation"
Dr Lena Palaniyappan, a Wellcome Trust Research Fellow, said: “In our daily life, we constantly switch between our inner, private world and the outer, objective world. This switching action is enabled by the connections between the insula and frontal cortex. This switch process appears to be disrupted in patients with schizophrenia. This could explain why internal thoughts sometime appear as external objective reality, experienced as voices or hallucinations in this condition. This could also explain the difficulties in ‘internalising’ external material pleasures (e.g. enjoying a musical tune or social events) that result in emotional blunting in patients with psychosis. Our observation offers a powerful mechanistic explanation for the formation of psychotic symptoms.”
Several brain regions are engaged when we are lost in thought or, for example, remembering a past event. However, when interrupted by a loud noise or another person speaking we are able to switch to using our frontal cortex area of the brain, which processes this external information. With a disruption in the connections from the insula, such switching may not be possible.
Compromised brain function
The Nottingham scientists used functional MRI (fMRI) imaging to compare the brains of 35 healthy volunteers with those of 38 schizophrenic patients. The results showed that whereas the majority of healthy patients were able to make this switch between regions, the patients with schizophrenia were less likely to shift to using their frontal cortex.
The insular and frontal cortex form a sensitive ‘salience’ loop within the brain — the insular should stimulate the frontal cortex while in turn the frontal cortex should inhibit the insula — but in patients with schizophrenia this system was found to be seriously compromised.
The results suggest that detecting the lack of a positive influence from the insula to the frontal cortex using fMRI could have a high degree of predictive value in identifying patients with schizophrenia.
The results of the study offer vital information for the development of more effective treatments for the condition.
Schizophrenia is one of the most common serious mental health conditions affecting around 1 in 100 people. Its onset occurs most commonly in a patient’s late teens or early 20s which can have devastating consequences for their future.
Genetic and environmental triggers
Scientists remain unsure what causes schizophrenia but believe it could be a combination of a genetic predisposition to the condition combined with environmental factors. Drug use is known to be a key trigger – people who use cannabis, or stimulant drugs, are three to four times more likely to go on to develop recurrent psychotic symptoms.
It is also believed that underdevelopment of the brain in the womb caused by complications in the mother’s pregnancy and in early childhood linked to issues such as malnutrition could play a key part. Previous observations from this research group have also uncovered the presence of unusually smooth folding patterns of the brain over the insula region in patients, suggesting an impairment in the normal development of this structure in schizophrenia.
At present, treatment involves a combination of antipsychotic medications, psychological therapies and social interventions. Currently, only one in five patients with schizophrenia achieve complete recovery and many patients who develop the condition in the long-term struggle to find a treatment that is 100 per cent effective in managing their condition.
Antipsychotic drugs, though effective in a number of patients, have poor acceptance rates due to the side effect burden meaning that many patients stop taking them in the longer run, leading to recurrence of disabling symptoms.
Researchers in Nottingham are also looking at a technique called TMS – transcranial magnetic stimulation — which uses a powerful magnetic pulse to stimulate the brain regions that are malfunctioning.
Compassion-based therapy
Despite the fact that the insular region is buried so deeply within the brain that TMS would usually be ineffective, the results of the Nottingham study suggest that the loop between the insular and the frontal cortex could be exploited for TMS– if a pulse is delivered to the frontal lobe it could stimulate the insula and reset the ‘switch’.
Other future treatment options could include the use of a compassion-based meditation therapy called mindfulness, which may have the potential to ‘reset’ the switching function of the insula and can promote physical changes within the brain. Meditation over a long period of time has been shown to increase the folding patterns within the insula area of the brain. These ideas are in its early stages at present, but may deliver more focussed treatment approaches in the longer term.
Playing video games can boost brain power
Certain types of video games can help to train the brain to become more agile and improve strategic thinking, according to scientists from Queen Mary University of London and University College London (UCL).
The researchers recruited 72 volunteers and measured their ‘cognitive flexibility’ described as a person’s ability to adapt and switch between tasks, and think about multiple ideas at a given time to solve problems.
Two groups of volunteers were trained to play different versions of a real-time strategy game called StarCraft, a fast-paced game where players have to construct and organise armies to battle an enemy. A third of the group played a life simulation video game called The Sims, which does not require much memory or many tactics.
All the volunteers played the video games for 40 hours over six to eight weeks, and were subjected to a variety of psychological tests before and after. All the participants happened to be female as the study was unable to recruit a sufficient number of male volunteers who played video games for less than two hours a week.
The researchers discovered that those who played StarCraft were quicker and more accurate in performing cognitive flexibility tasks, than those who played The Sims.
Dr Brian Glass from Queen Mary’s School of Biological and Chemical Sciences, said: “Previous research has demonstrated that action video games, such as Halo, can speed up decision making but the current work finds that real-time strategy games can promote our ability to think on the fly and learn from past mistakes.
“Our paper shows that cognitive flexibility, a cornerstone of human intelligence, is not a static trait but can be trained and improved using fun learning tools like gaming.”
Professor Brad Love from UCL, said: “Cognitive flexibility varies across people and at different ages. For example, a fictional character like Sherlock Holmes has the ability to simultaneously engage in multiple aspects of thought and mentally shift in response to changing goals and environmental conditions.
“Creative problem solving and ‘thinking outside the box’ require cognitive flexibility. Perhaps in contrast to the repetitive nature of work in past centuries, the modern knowledge economy places a premium on cognitive flexibility.”
Dr Glass added: “The volunteers who played the most complex version of the video game performed the best in the post-game psychological tests. We need to understand now what exactly about these games is leading to these changes, and whether these cognitive boosts are permanent or if they dwindle over time. Once we have that understanding, it could become possible to develop clinical interventions for symptoms related to attention deficit hyperactivity disorder or traumatic brain injuries, for example.”
(Source: qmul.ac.uk)
Researchers Identify Conditions Most Likely to Kill Encephalitis Patients
People with severe encephalitis — inflammation of the brain — are much more likely to die if they develop severe swelling in the brain, intractable seizures or low blood platelet counts, regardless of the cause of their illness, according to new Johns Hopkins research.
The Johns Hopkins investigators say the findings suggest that if physicians are on the lookout for these potentially reversible conditions and treat them aggressively at the first sign of trouble, patients are more likely to survive.
“The factors most associated with death in these patients are things that we know how to treat,” says Arun Venkatesan, M.D., Ph.D., an assistant professor of neurology at the Johns Hopkins University School of Medicine and leader of the study published in the Aug. 27 issue of the journal Neurology.
Experts consider encephalitis something of a mystery, and its origins and progress unpredictable. While encephalitis may be caused by a virus, bacteria or autoimmune disease, a precise cause remains unknown in 50 percent of cases. Symptoms range from fever, headache and confusion in some, to seizures, severe weakness or language disability in others. The most complex cases can land patients in intensive care units, on ventilators, for months. Drugs like the antiviral acyclovir are available for herpes encephalitis, which occurs in up to 15 percent of cases, but for most cases, doctors have only steroids and immunosuppressant drugs, which carry serious side effects.
“Encephalitis is really a syndrome with many potential causes, rather than a single disease, making it difficult to study,” says Venkatesan, director of the Johns Hopkins Encephalitis Center.
In an effort to better predict outcomes for his patients, Venkatesan and his colleagues reviewed records of all 487 patients with acute encephalitis admitted to The Johns Hopkins Hospital and Johns Hopkins Bayview Medical Center between January 1997 and July 2011. They focused further attention on patients who spent at least 48 hours in the ICU during their hospital stays and who were over the age of 16. Of those 103 patients, 19 died. Patients who had severe swelling in the brain were 18 times more likely to die, while those with continuous seizures were eight times more likely to die. Those with low counts in blood platelets, the cells responsible for clotting, were more than six times more likely to die than those without this condition.
The findings can help physicians know which conditions should be closely monitored and when the most aggressive treatments — some of which can come with serious side effects — should be tried, the researchers say. For example, it may be wise to more frequently image the brains of these patients to check for increased brain swelling and the pressure buildup that accompanies it.
Venkatesan says patients with cerebral edema may do better if intracranial pressure is monitored continuously and treated aggressively. He cautioned that although his research suggests such a course, further studies are needed to determine if it leads to better outcomes for patients.
Similarly, he says research has yet to determine whether aggressively treating seizures and low platelet counts also decrease mortality.
Venkatesan and his colleagues are also developing better guidelines for diagnosing encephalitis more quickly so as to minimize brain damage. Depending on where in the brain the inflammation is, he says, the illness can mimic other diseases, making diagnosis more difficult.
Another of the study’s co-authors, Romergryko G. Geocadin, M.D., an associate professor of neurology who co-directs the encephalitis center and specializes in neurocritical care, says encephalitis patients in the ICU are “the sickest of the sick,” and he fears that sometimes doctors give up on the possibility of them getting better.
“This research should give families — and physicians — hope that, despite how bad it is, it may be reversible,” he says.
(Source: newswise.com)
How sleep helps brain learn motor task
Sleep helps the brain consolidate what we’ve learned, but scientists have struggled to determine what goes on in the brain to make that happen for different kinds of learned tasks. In a new study, researchers pinpoint the brainwave frequencies and brain region associated with sleep-enhanced learning of a sequential finger tapping task akin to typing, or playing piano.
You take your piano lesson, you go to sleep and when you wake up your fingers are better able to play that beautiful sequence of notes. How does sleep make that difference? A new study helps to explain what happens in your brain during those fateful, restful hours when motor learning takes hold.
"The mechanisms of memory consolidations regarding motor memory learning were still uncertain until now," said Masako Tamaki, a postdoctoral researcher at Brown University and lead author of the study that appears Aug. 21 in the Journal of Neuroscience. “We were trying to figure out which part of the brain is doing what during sleep, independent of what goes on during wakefulness. We were trying to figure out the specific role of sleep.”
In part because it employed three different kinds of brain scans, the research is the first to precisely quantify changes among certain brainwaves and the exact location of that changed brain activity in subjects as they slept after learning a sequential finger-tapping task. The task was a sequence of key punches that is cognitively akin to typing or playing the piano.
Specifically, the results of complex experiments performed at Massachusetts General Hospital and then analyzed at Brown show that the improved speed and accuracy volunteers showed on the task after a few hours sleep was significantly associated with changes in fast-sigma and delta brainwave oscillations in their supplementary motor area (SMA), a region on the top-middle of the brain. These specific brainwave changes in the SMA occurred during a particular phase of sleep known as “slow-wave” sleep.
Scientists have shown that sleep improves many kinds of learning, including the kind of sequential finger-tapping motor tasks addressed in the study, but they haven’t been sure about why or how. It’s an intensive activity for the brain to consolidate learning and so the brain may benefit from sleep perhaps because more energy is available or because distractions and new inputs are fewer, said study corresponding author Yuka Sasaki, a research associate professor in Brown’s Department of Cognitive, Linguistic & Psychological Sciences.
"Sleep is not just a waste of time," Sasaki said.
The extent of reorganization that the brain accomplishes during sleep is suggested by the distinct roles the two brainwave oscillations appear to play. The authors wrote that the delta oscillations appeared to govern the changes in the SMA’s connectivity with other areas of the cortex, while the fast-sigma oscillations appeared to pertain to changes within the SMA itself.
Meticulous measurements
Possible roles for fast-sigma and delta brainwaves and for the SMA had suggestive support in the literature before this study, but no one had obtained much proof in part because doing so requires a complex experimental protocol.
To make their findings, Sasaki, Tamaki and their team asked each of their 15 subjects to volunteer for the motor learning experiments. For the first three nights, nine subjects simply slept at whatever their preferred bedtime was while their brains were scanned both with magnetoencephalography (MEG), which measures the oscillations with precise timing, and polysomnography, which keeps track of sleep phase. By this time the researchers had good baseline measurements of their brain activity and subjects had become accustomed to sleeping in the lab.
On day 4, the subjects learned the finger-tapping task on their non-dominant hand (to purposely make it harder to learn). The subjects were then allowed to go to sleep for three hours and were again scanned with PSG and MEG. Then the researchers woke them up. An hour later they asked the subjects to perform the tapping task. As a control, six other subjects did not sleep after learning the task, but were also asked to perform it four hours after being trained. Those who slept did the task faster and more accurately than those who did not.
On day 5, the researchers scanned each volunteer with an magnetic resonance imaging machine, which maps brain anatomy, so that they could later see where the MEG oscillations they had observed were located in each subject’s brain.
In all, the experimenters tracked 5 different oscillation frequencies in eight brain regions (four distinct regions on each of the brain’s two sides). Sasaki said she expected the most significant activity to take place in the “M1” brain region, which governs motor control, but instead the significant changes occurred in the SMA on the opposite side of the trained hand.
What was especially important about the delta and fast-sigma oscillations was that they fit two key criteria with statistical significance: they changed substantially after subjects were trained in the task and the strength of that change correlated with the degree of the subject’s performance improvement on the task.
After performing the experiments, the team of Sasaki, Tamaki and co-author Takeo Watanabe moved from MGH to Brown, where they have set up a new sleep lab. They have since begun a project to further study how the brain consolidates learning. In this case they’re looking at visual learning tasks.
"Will we see similar effects?" Sasaki asked. "Would it be with similar frequency bands and a similar organization of neighboring brain areas?"
To find out, some volunteers will just have to sleep on it.
How brain microcircuits integrate information from different senses
A new publication in the top-ranked journal Neuron sheds new light onto the unknown processes on how the brain integrates the inputs from the different senses in the complex circuits formed by molecularly distinct types of nerve cells. The work was led by new Umeå University associate professor Paolo Medini.
One of the biggest challenges in Neuroscience is to understand how the cerebral cortex of the brain processes and integrates the inputs from the different senses (like vision, hearing and touch) to control for example, that we can respond to an event in the environment with precise movement of our body.
The brain cortex is composed by morphologically and functionally different types of nerve cells, e.g. excitatory, inhibitory, that connect in very precise ways. Paolo Medini and co-workers show that the integration of inputs from different senses in the brain occurs differently in excitatory and inhibitory cells, as well as in superficial and in the deep layers of the cortex, the latter ones being those that send electrical signals out from the cortex to other brain structures.
“The relevance and the innovation of this work is that by combining advanced techniques to visualize the functional activity of many nerve cells in the brain and new molecular genetic techniques that allows us to change the electrical activity of different cell types, we can for the first time understand how the different nerve cells composing brain circuits communicate with each other”, says Paolo Medini.
The new knowledge is essential to design much needed future strategies to stimulate brain repair. It is not enough to transplant nerve cells in the lesion site, as the biggest challenge is to re-create or re-activate these precise circuits made by nerve cells.
Paolo Medini has a Medical background and worked in Germany at the Max Planck Institute for Medical Research of Heidelberg, as well as a Team leader at the Italian Institute of Technology in Genova, Italy. He recently started on the Associate Professor position in Cellular and Molecular Physiology at the Molecular Biology Department.
He is now leading a brand new Brain Circuits Lab with state of state-of-the-art techniques such as two-photon microscopy, optogenetics and electrophysiology to investigate the circuit functioning and repair in the brain cortex. This investment has been possible by a generous contribution from the Kempe Foundation and by the combined effort of Umeå University.
“By combining cell physiology knowledge in the intact brain with molecular biology expertise, we plan to pave the way for this kind of innovative research that is new to Umeå University and nationally”, says Paolo Medini.
(Source: teknat.umu.se)
A new role for sodium in the brain
Researchers at McGill University have found that sodium – the main chemical component in table salt – is a unique “on/off” switch for a major neurotransmitter receptor in the brain. This receptor, known as the kainate receptor, is fundamental for normal brain function and is implicated in numerous diseases, such as epilepsy and neuropathic pain.
Prof. Derek Bowie and his laboratory in McGill’s Department of Pharmacology and Therapeutics, worked with University of Oxford researchers to make the discovery. By offering a different view of how the brain transmits information, their research highlights a new target for drug development. The findings are published in the journal Nature Structural & Molecular Biology.
Balancing kainate receptor activity is the key to maintaining normal brain function. For example, in epilepsy, kainate activity is thought to be excessive. Thus, drugs which would shut down this activity are expected to be beneficial.
“It has been assumed for decades that the “on/off” switch for all brain receptors lies where the neurotransmitter binds,” says Prof. Bowie, who also holds a Canada Research Chair in Receptor Pharmacology. “However, we found a completely separate site that binds individual atoms of sodium and controls when kainate receptors get turned on and off.”
The sodium switch is unique to kainate receptors, which means that drugs designed to stimulate this switch, should not act elsewhere in the brain. This would be a major step forward, since drugs often affect many locations, in addition to those they were intended to act on, producing negative side-effects as a result. These so called “off-target effects” for drugs represent one of the greatest challenges facing modern medicine.
“Now that we know how to stimulate kainate receptors, we should be able to design drugs to essentially switch them off,” says Dr. Bowie.
Dr. Philip Biggin’s lab at Oxford University used computer simulations to predict how the presence or absence of sodium would affect the kainate receptor.
(Source: mcgill.ca)
Study suggests iron is at core of Alzheimer’s disease
Alzheimer’s disease has proven to be a difficult enemy to defeat. After all, aging is the No. 1 risk factor for the disorder, and there’s no stopping that.
Most researchers believe the disease is caused by one of two proteins, one called tau, the other beta-amyloid. As we age, most scientists say, these proteins either disrupt signaling between neurons or simply kill them.
Now, a new UCLA study suggests a third possible cause: iron accumulation.
Dr. George Bartzokis, a professor of psychiatry at the Semel Institute for Neuroscience and Human Behavior at UCLA and senior author of the study, and his colleagues looked at two areas of the brain in patients with Alzheimer’s. They compared the hippocampus, which is known to be damaged early in the disease, and the thalamus, an area that is generally not affected until the late stages. Using sophisticated brain-imaging techniques, they found that iron is increased in the hippocampus and is associated with tissue damage in that area. But increased iron was not found in the thalamus.
The research appears in the August edition of the Journal of Alzheimer’s Disease.
While most Alzheimer’s researchers focus on the buildup of tau or beta-amyloid that results in the signature plaques associated with the disease, Bartzokis has long argued that the breakdown begins much further “upstream.” The destruction of myelin, the fatty tissue that coats nerve fibers in the brain, he says, disrupts communication between neurons and promotes the buildup of the plaques. These amyloid plaques in turn destroy more and more myelin, disrupting brain signaling and leading to cell death and the classic clinical signs of Alzheimer’s.
Myelin is produced by cells called oligodendrocytes. These cells, along with myelin, have the highest levels of iron of any cells in the brain, Bartzokis says, and circumstantial evidence has long supported the possibility that brain iron levels might be a risk factor for age-related diseases like Alzheimer’s. Although iron is essential for cell function, too much of it can promote oxidative damage, to which the brain is especially vulnerable.
In the current study, Bartzokis and his colleagues tested their hypothesis that elevated tissue iron caused the tissue breakdown associated with Alzheimer’s disease. They targeted the vulnerable hippocampus, a key area of the brain involved in the formation of memories, and compared it to the thalamus, which is relatively spared by Alzheimer’s until the very late stages of disease.
The researchers used an MRI technique that can measure the amount of brain iron in ferritin, a protein that stores iron, in 31 patients with Alzheimer’s and 68 healthy control subjects.
In the presence of diseases like Alzheimer’s, as the structure of cells breaks down, the amount of water increases in the brain, which can mask the detection of iron, according to Bartzokis.
"It is difficult to measure iron in tissue when the tissue is already damaged," he said. "But the MRI technology we used in this study allowed us to determine that the increase in iron is occurring together with the tissue damage. We found that the amount of iron is increased in the hippocampus and is associated with tissue damage in patients with Alzheimer’s but not in the healthy older individuals — or in the thalamus. So the results suggest that iron accumulation may indeed contribute to the cause of Alzheimer’s disease."
But it’s not all bad news from this study, Bartzokis noted.
"The accumulation of iron in the brain may be influenced by modifying environmental factors, such as how much red meat and iron dietary supplements we consume and, in women, having hysterectomies before menopause," he said.
In addition, he noted, medications that chelate and remove iron from tissue are being developed by several pharmaceutical companies as treatments for the disorder. This MRI technology may allow doctors to determine who is most in need of such treatments.
(Source: newsroom.ucla.edu)