Tag: Neurology

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New insights into how the mind influences the body

Post author By Vetscite
Post date September 13, 2016

Neuroscientists at the University of Pittsburgh have identified the neural networks that connect the cerebral cortex to the adrenal medulla, which is responsible for the body’s rapid response in stressful situations. These findings, reported in the online Early Edition of the journal Proceedings of the National Academy of Sciences (PNAS), provide evidence for the neural basis of a mind-body connection.

Specifically, the findings shed new light on how stress, depression and other mental states can alter organ function, and show that there is a real anatomical basis for psychosomatic illness. The research also provides a concrete neural substrate that may help explain why meditation and certain exercises such as yoga and Pilates can be so helpful in modulating the body’s responses to physical, mental and emotional stress.

“Our results turned out to be much more complex and interesting than we imagined before we began this study,” said senior author Peter L. Strick, Ph.D., Thomas Detre Chair of the Department of Neurobiology and scientific director of the University of Pittsburgh Brain Institute.

In their experiments, the scientists traced the neural circuitry that links areas of the cerebral cortex to the adrenal medulla (the inner part of the adrenal gland, which is located above each kidney). The scientific team included lead author Richard P. Dum, Ph.D., research associate professor in the Department of Neurobiology; David J. Levinthal, M.D., Ph.D., assistant professor in the Department of Medicine; and Dr. Strick.

The scientists were surprised by the sheer number of neural networks they uncovered. Other investigators had suspected that one or, perhaps, two cortical areas might be responsible for the control of the adrenal medulla. The actual number and location of the cortical areas were uncertain. In the PNAS study, the Strick laboratory used a unique tracing method that involves rabies virus. This approach is capable of revealing long chains of interconnected neurons. Using this approach, Dr. Strick and his colleagues demonstrated that the control of the adrenal medulla originates from multiple cortical areas. According to the new findings, the biggest influences arise from motor areas of the cerebral cortex and from other cortical areas involved in cognition and affect.

Why does it matter which cortical areas influence the adrenal medulla? Acute responses to stress include a wide variety of changes such as a pounding heart, sweating and dilated pupils. These responses help prepare the body for action and often are characterized as “fight or flight responses.” Many situations in modern life call for a more thought-out reaction than simple “fight or flight,” and it is clear that we have some cognitive control (or what neuroscientists call “top-down” control) over our responses to stress.

“Because we have a cortex, we have options,” said Dr. Strick. “If someone insults you, you don’t have to punch them or flee. You might have a more nuanced response and ignore the insult or make a witty comeback. These options are part of what the cerebral cortex provides.”

Another surprising result was that motor areas in the cerebral cortex, involved in the planning and performance of movement, provide a substantial input to the adrenal medulla. One of these areas is a portion of the primary motor cortex that is concerned with the control of axial body movement and posture. This input to the adrenal medulla may explain why core body exercises are so helpful in modulating responses to stress. Calming practices such as Pilates, yoga, tai chi and even dancing in a small space all require proper skeletal alignment, coordination and flexibility.

The PNAS study also revealed that the areas of the cortex that are active when we sense conflict, or are aware that we have made an error, are a source of influence over the adrenal medulla. “This observation,” said Dr. Strick, “raises the possibility that activity in these cortical areas when you re-imagine an error, or beat yourself up over a mistake, or think about a traumatic event, results in descending signals that influence the adrenal medulla in just the same way as the actual event.” These anatomical findings have relevance for therapies that deal with post-traumatic stress.

Additional links with the adrenal medulla were discovered in cortical areas that are active during mindful mediation and areas that show changes in bipolar familial depression. “One way of summarizing our results is that we may have uncovered the stress and depression connectome,” says Dr. Strick.

Overall, these results indicate that circuits exist to link movement, cognition and affect to the function of the adrenal medulla and the control of stress. This circuitry may mediate the effects of internal states like chronic stress and depression on organ function and, thus, provide a concrete neural substrate for psychosomatic illness.

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/08/160815185555.htm Original web page at Science Daily

Tags Endocrinology, Human, Neurology

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Cognitive offloading: How the Internet is increasingly taking over human memory

Post author By Vetscite
Post date September 13, 2016

Our increasing reliance on the Internet and the ease of access to the vast resource available online is affecting our thought processes for problem solving, recall and learning. In a new article published in the journal Memory, researchers at the University of California, Santa Cruz and University of Illinois, Urbana Champaign have found that ‘cognitive offloading’, or the tendency to rely on things like the Internet as an aide-mémoire, increases after each use. We might think that memory is something that happens in the head but increasingly it is becoming something that happens with the help of agents outside the head. Benjamin Storm, Sean Stone & Aaron Benjamin conducted experiments to determine our likelihood to reach for a computer or smartphone to answer questions. Participants were first divided into two groups to answer some challenging trivia questions — one group used just their memory, the other used Google. Participants were then given the option of answering subsequent easier questions by the method of their choice.

The results revealed that participants who previously used the Internet to gain information were significantly more likely to revert to Google for subsequent questions than those who relied on memory. Participants also spent less time consulting their own memory before reaching for the Internet; they were not only more likely to do it again, they were likely to do it much more quickly. Remarkably 30% of participants who previously consulted the Internet failed to even attempt to answer a single simple question from memory.

Lead author Dr Benjamin Storm commented, “Memory is changing. Our research shows that as we use the Internet to support and extend our memory we become more reliant on it. Whereas before we might have tried to recall something on our own, now we don’t bother. As more information becomes available via smartphones and other devices, we become progressively more reliant on it in our daily lives.”

This research suggests that using a certain method for fact finding has a marked influence on the probability of future repeat behaviour. Time will tell if this pattern will have any further reaching impacts on human memory than has our reliance on other information sources. Certainly the Internet is more comprehensive, dependable and on the whole faster than the imperfections of human memory, borne out by the more accurate answers from participants in the internet condition during this research. With a world of information a Google search away on a smartphone, the need to remember trivial facts, figures, and numbers is inevitably becoming less necessary to function in everyday life.

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/08/160816085029.htm Original web page at Science Daily

Tags Human, Neurology

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Snakes have adapted their vision to hunt their prey day or night

Post author By Vetscite
Post date September 13, 2016

For example, snakes that need good eyesight to hunt during the day have eye lenses that act as sunglasses, filtering out ultraviolet light and sharpening their vision while nocturnal snakes have lenses that allow ultraviolet light through, helping them to see in the dark.

New insights into the relationship between ultraviolet (UV) filters and hunting methods in snakes is one of the findings of the first major study of visual pigment genes and lenses in snakes — published in the advanced online edition of Molecular Biology and Evolution.

The new research was an international collaboration between snake biologists and vision experts led by the David Gower and included fellow Natural History Museum researchers Bruno Simões and Filipa Sampaio. Much of the research, including most of the DNA analyses, was carried out in the Museum’s laboratories.

Scientists have long known that snakes have highly variable sets of rods and cones — the specialised cells in the retina that an animal uses to detect light. But until now, most modern studies of vision in vertebrates (animals with a backbone) have concentrated on mammals, birds and fish.

To see in different colors, animals use visual pigments in their rods and cones that are sensitive to different wavelengths of light. The researchers examined the genes involved in producing the pigments from a broad genomic survey of 69 different species of snakes. What they found was as the genes vary from species to species so does the exact molecular structure of the pigments and the wavelengths of light they absorb.

The new research discovered that most snakes possess three visual pigments and are likely dichromatic in daylight — seeing two primary colours rather than the three that most humans see.

However, it also discovered that snake visual pigment genes have undergone a great amount of adaptation, including many changes to the wavelengths of light that the pigments are sensitive to, in order to suit the diversity of lifestyles that snakes have evolved.

Most snakes examined in the new study are sensitive to UV light, which likely allows them to see well in low light conditions. For light to reach the retina and be absorbed by the pigments, it first travels through the lens of the eye. Snakes with UV-sensitive visual pigments therefore have lenses that let UV light though.

In contrast, the research showed that those snakes that rely on their eyesight to hunt in the daytime, such as the gliding golden tree snake Chrysopelea ornata and the Monypellier snake Malpolon monspessulanus, have lenses that block UV light. As well as perhaps helping to protect their eyes from damage, this likely helps sharpen their sight — in the same way that skiers’ yellow goggles cut out some blue light and improve contrast.

Moreover, these snakes with UV-filtering lenses have tuned the pigments in their retina so that they are no longer sensitive to the short UV light, but absorb longer wavelengths.

All nocturnal species examined (such as N America’s glossy snake Arizona elegans) were found to have lenses that do not filter UV. Some snake species active in daylight also lack a UV-filtering lens, perhaps because they are less reliant on very sharp vision or live in places without very bright light.

By analysing how the pigments have evolved in snakes, the new study concluded also that the most recent ancestor of all living snakes had UV sensitive vision. “The precise nature of the ancestral snake is contentious, but the evidence from vision is consistent with the idea that it was adapted to living in low light conditions on land,” said corresponding author Gower.

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/08/160816182620.htm Original web page at Science Daily

Tags Neurology, Ophthalmology, Reptiles

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No blue light, please, I’m tired: Light color determines sleepiness versus arousal in mice

Post author By Vetscite
Post date September 13, 2016

Light affects sleep. A study in mice published in Open Access journal PLOS Biology shows that the actual color of light matters; blue light keeps mice awake longer while green light puts them to sleep easily. An accompanying Primer provides accessible context information and discusses open questions and potential implications for “designing the lighting of the future.”

Light shining into our eyes not only mediates vision but also has critical non-image-forming functions such as the regulation of circadian rhythm, which affects sleep and other physiological processes. As humans, light generally keeps us awake, and dark makes us sleepy. For mice, which are mostly nocturnal, light is a sleep-inducer. Previous studies in mice and humans have shown that non-image-forming light perception occurs in specific photosensitive cells in the eye and involves a light sensor called melanopsin. Mice without melanopsin show a delay in their response to fall asleep when exposed to light, pointing to a critical role for melanopsin in sleep regulation.

Stuart Peirson and Russell Foster, both from Oxford University, UK, alongside colleagues from Oxford and elsewhere, investigated this further by studying sleep induction in mice exposed to colored light, i.e., light of different wave lengths. Based on the physical properties of melanopsin, which is most sensitive to blue light, the researchers predicted that blue light would be the most potent sleep inducer.

To their surprise, that was not the case. Green light, it turns out, puts mice to sleep quickly, whereas blue light actually seems to stimulate the mice, though they did fall asleep eventually. Mice lacking melanopsin were oblivious to light color, demonstrating that the protein is directing the differential response.

Both green and blue light elevated levels of the stress hormone corticosterone in the blood of exposed mice compared with mice kept in the dark, the researchers found. Corticosterone levels in response to blue light, however, were higher than levels in mice exposed to green light. When the researchers gave the mice drugs that block the effects of corticosterone, they were able to mitigate the effects of blue light; drugged mice exposed to blue light went to sleep faster than control mice that had received placebos.

Citing previous results that exposure to blue light — a predominant component of light emitted by computer and smart-phone screens — promotes arousal and wakefulness in humans as well, the researchers suggest that “despite the differences between nocturnal and diurnal species, light may play a similar alerting role in mice as has been shown in humans.” Overall, they say their work “shows the extent to which light affects our physiology and has important implications for the design and use of artificial light sources.”

In the accompanying Primer, Patrice Bourgin, from the University of Strasbourg, France, and Jeffrey Hubbard from the University of Lausanne, Switzerland, say the study “reveals that the role of color [in controlling sleep and alertness] is far more important and complex than previously thought, and is a key parameter to take into account.” The study’s results, they say, “call for a greater understanding of melanopsin-based phototransduction and tell us that color wavelength is another aspect of environmental illumination that we should consider, in addition to photon density, duration of exposure and time of day, as we move forward in designing the lighting of the future, aiming to improve human health and well-being.”

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/08/160815185816.htm Original web page at Science Daily

Tags Neurology, Ophthalmology, Rodents/Lags

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Zika infection may affect adult brain cells

Post author By Vetscite
Post date September 13, 2016

Concerns over the Zika virus have focused on pregnant women due to mounting evidence that it causes brain abnormalities in developing fetuses. However, new research in mice from scientists at The Rockefeller University and La Jolla Institute for Allergy and Immunology suggests that certain adult brain cells may be vulnerable to infection as well. Among these are populations of cells that serve to replace lost or damaged neurons throughout adulthood, and are also thought to be critical to learning and memory.

“This is the first study looking at the effect of Zika infection on the adult brain,” says Joseph Gleeson, adjunct professor at Rockefeller, head of the Laboratory of Pediatric Brain Disease, and Howard Hughes Medical Institute investigator. “Based on our findings, getting infected with Zika as an adult may not be as innocuous as people think.”

Although more research is needed to determine if this damage has long-term biological implications or the potential to affect behavior, the findings suggest the possibility that the Zika virus, which has become widespread in Central and South America over the past eight months, may be more harmful than previously believed. The new findings were published in Cell Stem Cell on August 18.

“Zika can clearly enter the brain of adults and can wreak havoc,” says Sujan Shresta, a professor at the La Jolla Institute of Allergy and Immunology. “But it’s a complex disease — it’s catastrophic for early brain development, yet the majority of adults who are infected with Zika rarely show detectable symptoms. Its effect on the adult brain may be more subtle, and now we know what to look for.”

Early in gestation, before our brains have developed into a complex organ with specialized zones, they are comprised entirely of neural progenitor cells. With the capability to replenish the brain’s neurons throughout its lifetime, these are the stem cells of the brain. In healthy individuals, neural progenitor cells eventually become fully formed neurons, and it is thought that at some point along this progression they become resistant to Zika, explaining why adults appear less susceptible to the disease.

But current evidence suggests that Zika targets neural progenitor cells, leading to loss of these cells and to reduced brain volume. This closely mirrors what is seen in microcephaly, a developmental condition linked to Zika infection in developing fetuses that results in a smaller-than-normal head and a wide variety of developmental disabilities.

The mature brain retains niches of these neural progenitor cells that appear to be especially impacted by Zika. These niches — in mice they exist primarily in two regions, the subventricular zone of the anterior forebrain and the subgranular zone of the hippocampus — are vital for learning and memory.

Gleeson and his colleagues suspected that if Zika can infect fetal neural progenitor cells, it wouldn’t be a far stretch for them to also be able to infect these cells in adults. In a mouse model engineered by Shresta and her team to mimic Zika infection in humans, fluorescent biomarkers illuminated to reveal that adult neural progenitor cells could indeed be hijacked by the virus.

“Our results are pretty dramatic — in the parts of the brain that lit up, it was like a Christmas tree,” says Gleeson. “It was very clear that the virus wasn’t affecting the whole brain evenly, like people are seeing in the fetus. In the adult, it’s only these two populations that are very specific to the stem cells that are affected by virus. These cells are special, and somehow very susceptible to the infection.”

The researchers found that infection correlated with evidence of cell death and reduced generation of new neurons in these regions. Integration of new neurons into learning and memory circuits is crucial for neuroplasticity, which allows the brain to change over time. Deficits in this process are associated with cognitive decline and neuropathological conditions, such as depression and Alzheimer’s disease.

Gleeson and colleagues recognize that healthy humans may be able to mount an effective immune response and prevent the virus from attacking. However, they suggest that some people, such as those weakened immune systems, may be vulnerable to the virus is a way that has not yet been recognized.

“In more subtle cases, the virus could theoretically impact long-term memory or risk of depression,” says Gleeson, “but tools do not exist to test the long-term effects of Zika on adult stem cell populations.”

In addition to microcephaly, Zika has been linked to Guillain-Barré syndrome, a rare condition in which the immune system attacks parts of the nervous system, leading to muscle weakness or even paralysis. “The connection has been hard to trace since Guillain-Barré usually develops after the infection has cleared,” says Shresta. “We propose that infection of adult neural progenitor cells could be the mechanism behind this.”

There are still many unanswered questions, including exactly how translatable findings in this mouse model are to humans. Gleeson’s findings in particular raise questions such as: Does the damage inflicted on progenitor cells by the virus have lasting biological consequences, and can this in turn affect learning and memory? Or, do these cells have the capability to recover? Nonetheless, these findings raise the possibility that Zika is not simply a transient infection in adult humans, and that exposure in the adult brain could have long-term effects.

“The virus seems to be traveling quite a bit as people move around the world,” says Gleeson. “Given this study, I think the public health enterprise should consider monitoring for Zika infections in all groups, not just pregnant women.”

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/08/160818131134.htm Original web page at Science Daily

Tags Human, Neurology, Virology

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Burnout is caused by mismatch between unconscious needs and job demands

Post author By Vetscite
Post date September 13, 2016

New research shows that burnout is caused by a mismatch between a person’s unconscious needs and the opportunities and demands at the workplace. These results have implications for the prevention of jobburnout.

Imagine an accountant who is outgoing and seeks closeness in her social relationships, but whose job offers little scope for contact with colleagues or clients. Now imagine a manager, required to take responsibility for a team, but who does not enjoy taking center-stage or being in a leadership role. For both, there is a mismatch between their individual needs and the opportunities and demands at the workplace. A new study in the open-access journal Frontiers in Psychology shows that such mismatches put employees at risk of burnout.

Burnout is a state of physical, emotional, and mental exhaustion from work, which results in a lack of motivation, low efficiency, and a helpless feeling. Its health effects include anxiety, cardiovascular disease, immune disorders, insomnia, and depression. The financial burden from absenteeism, employee turnover, reduced productivity, and medical, legal, and insurance expenses due to burnout and general work-related stress is staggering: for example, the American Institute of Stress estimates the total cost to American enterprises at 300 billion US$ per year, while a 2012 study commissioned by the Health Programme of the European Union estimates the annual cost to EU enterprises at 272 billion €.

In the new study, researchers from the Universities of Zurich and Leipzig show that the unconscious needs of employees — their so-called “implicit motives” — play an important role in the development of burnout. The researchers focus on two important motives: the power motive, that is, the need to take responsibility for others, maintain discipline, and engage in arguments or negotiation, in order to feel strong and self-efficacious; and the affiliation motive, the need for positive personal relations, in order to feel trust, warmth, and belonging. A mismatch between job characteristics and either implicit motive can cause burnout, the results show. Moreover, a mismatch in either direction is risky: employees can get burned out when they have too much or not enough scope for power or affiliation compared to their individual needs.

“We found that the frustration of unconscious affective needs, caused by a lack of opportunities for motive-driven behavior, is detrimental to psychological and physical well-being. The same is true for goal-striving that doesn’t match a well-developed implicit motive for power or affiliation, because then excessive effort is necessary to achieve that goal. Both forms of mismatch act as ‘hidden stressors’ and can cause burnout,” says the leading author, Veronika Brandstätter, Professor of Psychology at the University of Zurich, Switzerland.

Brandstätter and colleagues recruited 97 women and men between 22 and 62 through the Swiss Burnout website, an information resource and forum for Swiss people suffering from burnout. Participants completed questionnaires about their physical well-being, degree of burnout, and the characteristics of their job, including its opportunities and demands.

To assess implicit motives — whose strength varies from person to person, but which can’t be measured directly through self-reports since they are mostly unconscious — Brandstätter et al. used an inventive method: they asked the participants to write imaginative short stories to describe five pictures, which showed an architect, trapeze artists, women in a laboratory, a boxer, and a nightclub scene. Each story was analyzed by trained coders, who looked for sentences about positive personal relations between persons (thus expressing the affiliation motive) or about persons having impact or influence on others (expressing the power motive). Participants who used many such sentences in their story received a higher score for the corresponding implicit motive.

The greater the mismatch between someone’s affiliation motive and the scope for personal relations at the job, the higher the risk of burnout, show the researchers. Likewise, adverse physical symptoms, such as headache, chest pain, faintness, and shortness of breath, became more common with increasing mismatch between an employee’s power motive and the scope for power in his or her job.

Importantly, these results immediately suggest that interventions that prevent or repair such mismatches could increase well-being at work and reduce the risk of burnout.

“A starting point could be to select job applicants in such a way that their implicit motives match the characteristics of the open position. Another strategy could be so-called “job crafting,” where employees proactively try to enrich their job in order to meet their individual needs. For example, an employee with a strong affiliation motive might handle her duties in a more collaborative way and try to find ways to do more teamwork,” says Brandstätter.

“A motivated workforce it the key to success in today’s globalized economy. Here, we need innovative approaches that go beyond providing attractive working conditions. Matching employees’ motivational needs to their daily activities at work might be the way forward. This may also help to address growing concerns about employee mental health, since burnout is essentially an erosion of motivation. To do so, we must increasingly take account of motivational patterns in the context of occupational stress research, and study person-environment-fit across entire organizations and industries,” says Beate Schulze, a Senior Researcher at the Department of Social and Occupational Medicine of the University of Leipzig and Vice-President of the Swiss Expert Network on Burnout.

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/08/160811171643.htm Original web page at Science Daily

Tags Behaviour (Ethology), Human, Neurology

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Novel compounds arrested epilepsy development in mice

Post author By Vetscite
Post date September 13, 2016

A team led by Nicolas Bazan, MD, PhD, Boyd Professor and Director of LSU Health New Orleans’ Neuroscience Center of Excellence, has developed neuroprotective compounds that may prevent the development of epilepsy. The findings will be published online in Scientific Reports, a Nature journal, on July 22, 2016.

In this study in an experimental model of epilepsy in mice, the compounds prevented seizures and their damaging effects on dendritic spines, specialized structures that allow brain cells to communicate. In epilepsy, these structures are damaged and rewire incorrectly, creating brain circuits that are hyper-connected and prone to seizures, an important example of pathological plasticity.

“In the current study, preservation of dendritic spines and subsequent protection from seizures, were observed up to 100 days post-treatment, suggesting the process of epilepsy development has been arrested,” notes Dr. Nicolas Bazan, Director of the LSU Health New Orleans Neuroscience Center of Excellence.

Dr. Bazan and Professor Julio Alvarez-Builla Gomez, a medicinal chemist from the University of Alcala in Spain, discovered and patented the LAU compounds, named for the inventors in Louisiana and the Spanish university. A number of LAU compounds were studied in this research, which blocked a neuroinflammatory signaling receptor, protecting dendritic spines and lessening seizure susceptibility and onset, as well as hyper-excitability.

According to the National Institutes of Health, the epilepsies are a spectrum of brain disorders ranging from severe, life-threatening and disabling, to ones that are much more benign. In epilepsy, the normal pattern of neuronal activity becomes disturbed, causing strange sensations, emotions, and behavior or sometimes convulsions, muscle spasms, and loss of consciousness. It is not uncommon for people with epilepsy, especially children, to develop behavioral and emotional problems in conjunction with seizures. Issues may also arise as a result of the stigma attached to having epilepsy, which can lead to embarrassment and frustration or bullying, teasing, or avoidance in school and other social settings. For many people with epilepsy, the risk of seizures restricts their independence (some states refuse drivers licenses to people with epilepsy) and recreational activities. Epilepsy can be a life-threatening condition. Some people with epilepsy are at special risk for abnormally prolonged seizures or sudden unexplained death in epilepsy. There is currently no cure.

The research was supported by the National Institute of General Medical Sciences of the National Institutes of Health. “Future clinical studies would evaluate the potential application of the compounds that we have developed and/or the mechanisms that we have discovered that are targeted by these compounds in the development of epilepsy,” concludes Dr. Bazan. “Most of the anti-epileptic drugs currently available treat the symptom – seizures- not the disease itself. Understanding the potential therapeutic usefulness of compounds that may interrupt the development process may pave the way for disease-modifying treatments for patients at risk for epilepsy.”

The research is part of an ongoing effort in Dr. Bazan laboratory to understand the critical role of brain plasticity which underlies many aspects of health and disease, from developmental disorders like dyslexia to aging, retinal degeneration, neurotrauma (concussions, TBI), stroke, Parkinson’s and Alzheimer’s disease.

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/07/160722092930.htm Original web page at Science Daily

Tags Neurology, Pharmacology, Rodents/Lags

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Antibiotics weaken Alzheimer’s disease progression through changes in the gut microbiome

Post author By Vetscite
Post date August 30, 2016

Long-term treatment with broad spectrum antibiotics decreased levels of amyloid plaques, a hallmark of Alzheimer’s disease, and activated inflammatory microglial cells in the brains of mice in a new study by neuroscientists from the University of Chicago.

The study, published July 21, 2016, in Scientific Reports, also showed significant changes in the gut microbiome after antibiotic treatment, suggesting the composition and diversity of bacteria in the gut play an important role in regulating immune system activity that impacts progression of Alzheimer’s disease.

“We’re exploring very new territory in how the gut influences brain health,” said Sangram Sisodia, PhD, Thomas Reynolds Sr. Family Professor of Neurosciences at the University of Chicago and senior author of the study. “This is an area that people who work with neurodegenerative diseases are going to be increasingly interested in, because it could have an influence down the road on treatments.”

Two of the key features of Alzheimer’s disease are the development of amyloidosis, accumulation of amyloid-ß (Aß) peptides in the brain, and inflammation of the microglia, brain cells that perform immune system functions in the central nervous system. Buildup of Aß into plaques plays a central role in the onset of Alzheimer’s, while the severity of neuro-inflammation is believed to influence the rate of cognitive decline from the disease.

For this study, Sisodia and his team administered high doses of broad-spectrum antibiotics to mice over five to six months. At the end of this period, genetic analysis of gut bacteria from the antibiotic-treated mice showed that while the total mass of microbes present was roughly the same as in controls, the diversity of the community changed dramatically. The antibiotic-treated mice also showed more than a two-fold decrease in Aß plaques compared to controls, and a significant elevation in the inflammatory state of microglia in the brain. Levels of important signaling chemicals circulating in the blood were also elevated in the treated mice.

While the mechanisms linking these changes is unclear, the study points to the potential in further research on the gut microbiome’s influence on the brain and nervous system.

“We don’t propose that a long-term course of antibiotics is going to be a treatment — that’s just absurd for a whole number of reasons,” said Myles Minter, PhD, a postdoctoral scholar in the Department of Neurobiology at UChicago and lead author of the study. “But what this study does is allow us to explore further, now that we’re clearly changing the gut microbial population and have new bugs that are more prevalent in mice with altered amyloid deposition after antibiotics.”

The study is the result of one the first collaborations from the Microbiome Center, a joint effort by the University of Chicago, the Marine Biological Laboratory and Argonne National Laboratory to support scientists at all three institutions who are developing new applications and tools to understand and harness the capabilities of microbial systems across different fields. Sisodia, Minter and their team worked with Eugene B. Chang, Martin Boyer Professor of Medicine at UChicago, and Vanessa Leone, PhD, a postdoctoral scholar in Chang’s lab, to analyze the gut microbes of the mice in this study.

Minter said the collaboration was enabling, and highlighted the cross-disciplinary thinking necessary to tackle a seemingly intractable disease like Alzheimer’s. “Once you put ideas together from different fields that have largely long been believed to be segregated from one another, the possibilities are really amazing,” he said.

Sisodia cautioned that while the current study opens new possibilities for understanding the role of the gut microbiome in Alzheimer’s disease, it’s just a beginning step.

“There’s probably not going to be a cure for Alzheimer’s disease for several generations, because we know there are changes occurring in the brain and central nervous system 15 to 20 years before clinical onset,” he said. “We have to find ways to intervene when a patient starts showing clinical signs, and if we learn how changes in gut bacteria affect onset or progression, or how the molecules they produce interact with the nervous system, we could use that to create a new kind of personalized medicine.”

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/07/160721072559.htm Original web page at Science Daily

Tags Neurology, Rodents/Lags

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Seeing structure that allows brain cells to communicate

Post author By Vetscite
Post date August 30, 2016

For more than a century, neuroscientists have known that nerve cells talk to one another across the small gaps between them, a process known as synaptic transmission (synapses are the connections between neurons). Information is carried from one cell to the other by neurotransmitters such as glutamate, dopamine, and serotonin, which activate receptors on the receiving neuron to convey excitatory or inhibitory messages.

But beyond this basic outline, the details of how this crucial aspect of brain function occurs have remained elusive. Now, new research by scientists at the University of Maryland School of Medicine (UM SOM) has for the first time elucidated details about the architecture of this process. The paper was published today in the journal Nature.

Synapses are very complicated molecular machines. They are also tiny: only a few millionths of an inch across. They have to be incredibly small, since we need a lot of them; the brain has around 100 trillion of them, and each is individually and precisely tuned to convey stronger or weaker signals between cells.

To visualize features on this sub-microscopic scale, the researchers turned to an innovative technology known as single-molecule imaging, which can locate and track the movement of individual protein molecules within the confines of a single synapse, even in living cells. Using this approach, the scientists identified an unexpected and precise pattern in the process of neurotransmission. The researchers looked at cultured rat synapses, which in terms of overall structure are very similar to human synapses.

“We are seeing things that have never been seen before. This is a totally new area of investigation,” said Thomas Blanpied, PhD, Associate Professor in the Department of Physiology, and leader of the group that performed the work. “For many years, we’ve had a list of the many types of molecules that are found at synapses, but that didn’t get us very far in understanding how these molecules fit together, or how the process really works structurally. Now by using single-molecule imaging to map where many of the key proteins are, we have finally been able to reveal the core architectural structure of the synapse.”

In the paper, Blanpied describes an unexpected aspect to this architecture that may explain why synapses are so efficient, but also susceptible to disruption during disease: at each synapse, key proteins are organized very precisely across the gap between cells. “The neurons do a better job than we ever imagined of positioning the release of neurotransmitter molecules near their receptors,” Blanpied says. “The proteins in the two different neurons are aligned with incredible precision, almost forming a column stretching between the two cells.” This proximity optimizes the power of the transmission, and also suggests new ways that this transmission can be modified.

Understanding this architecture will help clarify how communication within the brain works, or, in the case of psychiatric or neurological disease, how it fails to work. Blanpied is also focusing on the activity of “adhesion molecules,” which stretch from one cell to the other and may be important pieces of the “nano-column.” He suspects that if adhesion molecules are not placed correctly at the synapse, synapse architecture will be disrupted, and neurotransmitters

won’t be able to do their jobs. Blanpied hypothesizes that in at least some disorders, the issue may be that even though the brain has the right amount of neurotransmitter, the synapses don’t transmit these molecules efficiently.

Blanpied says that this improved comprehension of synaptic architecture could lead to a better understanding of brain diseases such as depression, schizophrenia and Alzheimer’s disease, and perhaps suggest new ideas for treatments.

Blanpied and his colleagues will next explore whether the synaptic architecture changes in certain disorders: they will begin by looking at a synapses in a mouse model of the pathology in schizophrenia.

https://www.sciencedaily.com/ Science Dail

https://www.sciencedaily.com/releases/2016/07/160727140303.htm Original web page at Science Daily

Tags Neurology, Rodents/Lags

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Why brain neurons in Parkinson’s disease stop benefiting from levodopa

Post author By Vetscite
Post date August 30, 2016

Though the drug levodopa can dramatically improve Parkinson’s disease symptoms, within five years one-half of the patients using L-DOPA develop an irreversible condition — involuntary repetitive, rapid and jerky movements. This abnormal motor behavior appears only while taking L-DOPA, and it stops if the drug is stopped. However, if L-DOPA is taken again, even many months later, it quickly re-emerges.

In research to prevent this side effect and extend the usefulness of L-DOPA — which is the most effective drug treatment for Parkinson’s disease — University of Alabama at Birmingham researchers have uncovered an essential mechanism of this long-term memory for L-DOPA-induced-dyskinesia, or LID.

They report a widespread reorganization of DNA methylation — a process in which the function of DNA is modified — in brain cells caused by L-DOPA. They also found that treatments that increase or decrease DNA methylation can alter dyskinesia symptoms in an animal model.

Thus, modification of DNA methylation may be a novel therapeutic target to prevent or reverse LID behavior.

“L-DOPA is a very valuable treatment for Parkinson’s, but in many patients its use is limited by dyskinesia,” said David Standaert, M.D., Ph.D., the John N. Whitaker Professor and chair of the Department of Neurology at UAB. “Better means of preventing or reversing LID could greatly extend the use of L-DOPA without inducing intolerable side effects. The treatments we have used here, methionine supplementation or RG-108, are not practical for human use; but they point to the opportunity to develop methylation-based epigenetic therapeutics in Parkinson’s disease.”

The research by David Figge, Karen Eskow Jaunarajs, Ph.D., and corresponding author David Standaert, Center for Neurodegeneration and Experimental Therapeutics, UAB Department of Neurology, was recently published in The Journal of Neuroscience.

Although studies of LID in animal models have shown changes in gene expression and cell signaling, a key unanswered question still remained: Why is the neural sensitization seen in LID persistent when delivery of L-DOPA is transient?

The UAB researchers suspected DNA methylation changes — the attachment of a methyl group onto nucleotides in DNA — because methylation is known to stably alter gene expression in cells as they grow and differentiate. Furthermore, methylation changes in neurons have been shown to be involved during the formation of place memory and the development of addictive behavior after cocaine use.

In general, increased DNA methylation has a silencing effect on nearby gene expression, while removal of the methyl groups enhances gene expression.

Figge and colleagues found that:

L-DOPA treatment of parkinsonian rodents enhanced the expression of two DNA demethylases.

Cells in the dorsal striatum in the LID model showed extensive, location-specific changes in DNA methylation, mostly seen as demethylation.The changes in DNA methylation were near many genes with established functional importance in LID.

Modulating global DNA methylation — either by injecting methionine to increase methylation or applying RG-108, an inhibitor of methylation, to the striatum — modified the dyskinetic behavior of LID, down or up, respectively.

“Together,” the researchers wrote, “these findings demonstrate that L-DOPA induces widespread changes to striatal DNA methylation and that these modifications are required for the development and maintenance of LID.”

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/07/160728143608.htm Original web page at Science Daily

Tags Genetics, Neurology, Rodents/Lags

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How birds soar to great heights

Post author By Vetscite
Post date August 30, 2016

Migratory birds often use warm, rising atmospheric currents to gain height with little energy expenditure when flying over long distances.

It’s a behavior known as thermal soaring that requires complex decision-making within the turbulent environment of a rising column of warm air from the sun baked surface of the earth.

But exactly how birds navigate within this ever-changing environment to optimize their thermal soaring was unknown until a team of physicists and biologists at the University of California San Diego took an exacting computational look at the problem.

In this week’s online version of the journal Proceedings of the National Academy of Sciences, the scientists demonstrated with mathematical models how glider pilots might be able to soar more efficiently by adopting the learning strategies that birds use to navigate their way through thermals.

“Relatively little is known about the navigation strategies used by birds to cope with these challenging conditions, mainly because past computational research examined soaring in unrealistically simplified situations,” explained Massimo Vergassola, a professor of physics at UC San Diego.

To tackle the problem, he and his colleagues, including Terrence Sejnowski, a professor of neurobiology at the Salk Institute and UC San Diego, combined numerical simulations of atmospheric flow with “reinforcement learning algorithms” — equations originally developed to model the behavior and improved performance of animals learning a new task. Those algorithms were developed in a manner that trained a glider to navigate complex turbulent environments based on feedback on the glider’s soaring performance.

According to Sejnowski, the “reinforcement learning architecture” was the same as that used by Google’s DeepMind AlphaGo program, which made headlines in 2016 after beating the human professional Go player Lee Sedol.

When applying it to soaring performance, the researchers took into account the bank angle and the angle of attack of the glider’s wings as well as how the temperature variations within the thermal impacted vertical velocity.

“By sensing two environmental cues — vertical wind acceleration and torque — the glider is able to climb and stay within the thermal core, where the lift is typically the largest, resulting in improved soaring performance, even in the presence of strong turbulent fluctuations,” said Vergassola. “As turbulent levels rise, the glider can avoid losing height by adopting increasingly conservative, risk-averse flight strategies, such as continuing along the same path rather than turning.”

The researchers write in their paper that, based on their study, “torque and vertical accelerations” appear to be the sensorimotor cues that most effectively guide the most efficient soaring path of birds through thermals, rather than differences in temperature.

“Temperature was specifically shown to yield minor gains,” they write adding that “a sensor of temperature could then be safely spared in the instrumentation for autonomous flying vehicles.”

“Our findings shed light on the decision-making processes that birds might use to successfully navigate thermals in turbulent environments,” said Vergassola. “This information could guide the design of simple mechanical instrumentation that would allow autonomous gliders to travel long distances with minimal energy consumption.”

“The high levels of soaring performance demonstrated in simulated turbulence could lead to the development of energy efficient autonomous gliders,” said Sejnowski, who is also a Howard Hughes Medical Institute Investigator.

Other members of the research team were Gautam Reddy, a physicist at UC San Diego and the first author of the paper, and Antonio Celani of the Abdus Salam International Center for Theoretical Physics in Trieste, Italy. The study was supported by a grant from the Simons Foundation.

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/08/160801163844.htm Original web page at Science Daily

Tags Birds (pet; ornamental; prey e.g. falcons), Neurology, Physiology (e.g. Exercise Physiology)

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Why is cocaine so addictive? Study using animal model provides clues

Post author By Vetscite
Post date August 30, 2016

Scientists at Wake Forest Baptist Medical Center are one step closer to understanding what causes cocaine to be so addictive. The research findings are published in the current issue of the Journal of Neuroscience.

Cocaine addiction is a debilitating neurological disorder that affects more than 700,000 people in the United States alone, according to the Substance Abuse and Mental Health Services Administration. With repeated use, tolerance may develop, meaning more of the drug is required to achieve the same euphoric effect. Cocaine addiction can be characterized by repeated attempts at abstinence that often end in relapse.

“Scientists have known for years that cocaine affects the dopamine system and dopamine transporters, so we designed our study to gain a better understanding of how tolerance to cocaine develops via the dopamine transporters,” said Sara R. Jones, Ph.D., professor of physiology and pharmacology at Wake Forest Baptist and lead author of the study.

“Currently there isn’t any effective treatment available for cocaine addiction so understanding the underlying mechanism is essential for targeting potential new treatments.”

Using an animal model, the research team replicated cocaine addiction by allowing rats to self-administer as much cocaine as they wanted (up to 40 doses) during a six-hour period. Six-hour-a-day access is long enough to cause escalation of intake and tip animals over from having controlled intake to more uncontrolled, binge-like behavior, Jones said.

Following the five-day experiment, the animals were not allowed cocaine for 14 or 60 days. After the periods of abstinence, the researchers looked at the animals’ dopamine transporters and they appeared normal, just like those in the control animals that had only received saline.

However, a single self-administered infusion of cocaine at the end of abstinence, even after 60 days, fully reinstated tolerance to cocaine’s effects in the animals that had binged. In the control animals that had never received cocaine, a single dose did not have the same effect.

These data demonstrate that cocaine leaves a long-lasting imprint on the dopamine system that is activated by re-exposure to cocaine, Jones said. This ‘priming effect,’ which may be permanent, may contribute to the severity of relapse episodes in cocaine addicts.

“Even after 60 days of abstinence, which is roughly equivalent to four years in humans, it only took a single dose of cocaine to put the rats back to square one with regard to its’ dopamine system and tolerance levels, and increased the likelihood of binging again,” Jones said. “It’s that terrible cycle of addiction.”

Jones added that hope is on the horizon through preclinical trials that are testing several amphetamine-like drugs for effectiveness in treating cocaine addiction.

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/08/160801163906.htm Original web page at Science Daily

Tags Neurology, Pharmacology, Rodents/Lags

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What can a sea-lion teach us about musicality?

Post author By Vetscite
Post date August 30, 2016

Ronan the sea lion can keep the beat better than any other animal, a study published in Frontiers in Neuroscience found out more.

Whether it is Mozart, Hendrix, Miles Davis, or tribal drumming, few activities feel as uniquely human as music. And, indeed, for a long time, most scientists believed that Homo sapiens was the only species capable of creating and responding to rhythm and melody.

This view, however, was challenged profoundly in 2009, when a cockatoo called Snowball was shown to be an able dancer.

Snowball bopping along to pop songs clearly demonstrated that non-human species had the neurobiological apparatus required to process rhythmic stimuli and move in time them.

And now — following investigations that have shown that chimps, bonobos, parrots and budgerigars have similar capabilities — a study of a head-bobbing Californian sea lion called Ronan has provided data that may aid scientists in their quest to understand the biological roots of musicality.

Ronan was placed in captivity when she was about a year old after failing to thrive in the wild. Her new team of keepers had previously explored the cognitive abilities of sea lions, and in what was originally a side-project explored at weekends, Peter Cook and Andrew Rouse decided to see if Ronan could keep a beat.

Rewarding her with fish treats every time she successfully nodded along to a click track, Cook and Rouse eventually found that Ronan could beat-keep better than any other non-human animal. Later, she learnt to dance to pop songs too; her favourite is Earth, Wind and Fire’s Boogie Wonderland.

They published an initial report in 2013 documenting this skill, which included numerous control experiments that confirmed that she was truly responding to the rhythmic input. And now in a paper in Frontiers in Neuroscience, Rouse and the team take their analysis a step further.

“A lot of the work that has been done on beat-keeping in general — to show whether a person or an animal is entrained — has used an observational approach, which looks at how close the animal is to each individual beat,” explains Rouse. But such studies “don’t reveal any underlying cause.”

To probe the brain mechanisms responsible for beat-keeping, Rouse says you must, “get a person or animal moving to the beat, then change the rhythm suddenly and look at how they adapt to the change, how they find the beat again.”

This is what they did. After shifting either the tempo or phase of the click track that Ronan was bobbing her head to, the researchers carefully charted how her movements were recalibrated. Something they also did by playing Boogie Wonderland at different speeds. And then they tested if a simple mathematical equation could account for the data.

The equation they used was from the physics of coupled oscillators — which can be as stripped down as two swinging pendulums. Applying this to the brain, the theory behind the experiment is that to move in time to music, the neural activity in auditory brain centres first oscillates in synchrony with the rhythmic input and then this oscillation entrains an oscillation in the neurons of the motor centres that drive movement.

This idea lies at the core of the neural resonance theory of music. And previous studies in people had shown that the equation describes well human beat-keeping. Rouse says that they asked, “Does Ronan’s behaviour fit this proposed model? And we found that it does.”

One thing that is important about Ronan is that sea lions are not “vocal mimics.” All the previous animals that had been shown to have beat-keeping abilities had been of species that have vocal flexibility.

This suggested that perhaps the skill was dependent on specialised neural circuits that are required for vocal flexibility. Ronan’s achievements and their accordance with an equation that simply describes two oscillating entities (in this case, oscillating populations of active neurons) suggest that the neural underpinnings of beat-keeping may be more ancient and widespread than previously thought.

Here, though, Rouse is cautious, he says the work doesn’t specifically distinguish between theories of musicality. He says we need to look further at all theories but that this opens up “a new avenue of exploration.”

Discussing why it took so long to appreciate the beat-keeping ability of non-human creatures, and the possibility that it is a skill lying dormant in many animals, Rouse discusses just how much practice humans get; how deeply and widely music is embedded in human culture. From a very early age babies are bounced on their mothers’ knees, they are exposed to nursery rhymes and music is all around them. “This coupling between auditory and motor regions, we have kind of beaten into us from day one,” he says, “Other animals don’t.”

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/08/160802125610.htm Original web page at Science Daily

Tags Neurology, Zoo/Wildlife

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How birds unlock their super-sense, ultraviolet vision

Post author By Vetscite
Post date August 10, 2016

The ability of finches, sparrows, and many other birds to see a visual world hidden to us is explained in a study published in the journal eLife.

Birds can be divided into those that can see ultraviolet (UV) light and those that cannot. Those that can live in a sensory world apart, able to transmit and receive signals between each other in a way that is invisible to many other species. How they unlock this extra dimension to their sight is revealed in new findings from the Washington University School of Medicine in St. Louis.

The study reveals two essential adaptions that enable birds to expand their vision into the UV range: chemical changes in light-filtering pigments called carotenoids and the tuning of light-sensitive proteins called opsins.

Birds acquire carotenoids through their diets and process them in a variety of ways to shift their light absorption toward longer or shorter wavelengths. The researchers characterized the carotenoid pigments from birds with violet vision and from those with UV vision and used computational models to see how the pigments affect the number of colors they can see.

“There are two types of light-sensitive cells, called photoreceptors, in the eye: rods and cones. Cone photoreceptors are responsible for color vision. While humans have blue, green, and red-sensitive cones only, birds have a fourth cone type which is either violet or UV-sensitive, depending on the species,” says senior author Joseph Corbo, MD, PhD, Associate Professor of Pathology and Immunology.

“Our approach showed that blue-cone sensitivity is fine-tuned through a change in the chemical structure of carotenoid pigments within the photoreceptor, allowing both violet and UV-sighted birds to maximize how many colors they can see.”

The study also revealed that sensitivity of the violet/UV cone and the blue cone in birds must move in sync to allow for optimum vision. Among bird species, there is a strong relationship between the light sensitivity of opsins within the violet/UV cone and mechanisms within the blue cone, which coordinate to ensure even UV vision.

Taken together, these results suggest that both blue and violet cone cells have adapted during evolution to enhance color vision in birds.

“The majority of bird species rely on vision as their primary sense, and color discrimination plays a crucial role in their essential behaviors, such as choosing mates and foraging for food. This explains why birds have evolved one of the most richly endowed color vision systems among vertebrates,” says first author Matthew Toomey, a postdoctoral fellow at the Washington University School of Medicine.

“The precise coordination of sensitivity and filtering in the visual system may, for example, help female birds discriminate very fine differences in the elaborate coloration of their suitors and choose the fittest mates. This refinement of visual sensitivity could also facilitate the search for hidden seeds, fruits, and other food items in the environment.”

The team now plans to investigate the underlying molecular mechanisms that help modify the carotenoid pigments and light-sensitive protein tuning in a wide range of bird species, to gather further insights into the evolution of UV vision.

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/07/160712093355.htm Original web page at Science Daily

Tags Birds (pet; ornamental; prey e.g. falcons), Neurology, Ophthalmology

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Scientists move closer to developing therapeutic window to the brain

Post author By Vetscite
Post date August 10, 2016

Researchers at the University of California, Riverside are bringing their idea for a ‘Window to the Brain’ transparent skull implant closer to reality through the findings of two studies that are forthcoming in the journals Lasers in Surgery and Medicine and Nanomedicine: Nanotechnology, Biology and Medicine.

The implant under development, which literally provides a ‘window to the brain,’ will allow doctors to deliver minimally invasive, laser-based treatments to patients with life-threatening neurological disorders, such as brain cancers, traumatic brain injuries, neurodegenerative diseases and stroke. The recent studies highlight both the biocompatibility of the implant material and its ability to endure bacterial infections.

The Window to the Brain project is a multi-institution, interdisciplinary partnership led by Guillermo Aguilar, professor of mechanical engineering in UCR’s Bourns College of Engineering, and Santiago Camacho-López, from the Centro de Investigación Científica y de Educación Superior de Ensenada (CICESE) in Mexico.

The project began when Aguilar and his team developed a transparent version of the material yttria-stabilized zirconia (YSZ) — the same ceramic product used in hip implants and dental crowns. By using this as a window-like implant, the team hopes doctors will be able to aim laser-based treatments into patients’ brains on demand and without having to perform repeated craniotomies, which are highly invasive procedures used to access the brain.

The internal toughness of YSZ, which is more impact resistant than glass-based materials developed by other researchers, also makes it the only transparent skull implant that could conceivably be used in humans. The two recent studies further support YSZ as a promising alternative for currently available cranial implants.

Published July 8 in Lasers in Surgery and Medicine, the most recent study demonstrates how the use of transparent YSZ may allow doctors to combat bacterial infections, which are a leading reason for cranial implant failure. In lab studies, the researchers treated E-Coli infections by aiming laser light through the implant without having to remove it and without damaging the surrounding tissues.

“This was an important finding because it showed that the combination of our transparent implant and laser-based therapies enables us to treat not only brain disorders, but also to tackle bacterial infections that are common after cranial implants. These infections are especially challenging to treat because many antibiotics do not penetrate the blood brain barrier,” said Devin Binder, M.D., a neurosurgeon and neuroscientist in UCR’s School of Medicine and a collaborator on the project.

Another recent study, published in the journal Nanomedicine: Nanotechnology, Biology and Medicine, explored the biocompatibility of YSZ in an animal model, where it integrated into the host tissue without causing an immune response or other adverse effects.

“The YSZ was actually found to be more biocompatible than currently available materials, such as titanium or thermo-plastic polymers, so this was another piece of good news in our development of transparent YSZ as the material of choice for cranial implants,” Aguilar said.

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/07/160712133916.htm Original web page at Science Daily

Tags Human, Neurology, Soft Tissue Surgery

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Ravens learn best from their affiliates

Post author By Vetscite
Post date August 10, 2016

Transmission of information from one individual to another forms the basis of long-term traditions and culture, and is critical in adjusting to changing environmental conditions. Animals frequently observe each other to learn about food, predators and their social environment. The study fills an important gap in our understanding of how different types of social connections affect animals’ ability to learn from the behavior of others.

Social connections range from aggressive interactions to the affiliative behaviors that are critical in forming strong social bonds. Human social behavior is frequently analyzed as social networks to capture its extent and complexity. By adopting a similar approach for ravens and analyzing their social networks, Christine Schwab and Thomas Bugnyar found that not all social connections are equally effective at influencing observation and learning. In particular, networks based on affiliative behaviors (sitting close to and preening each other, sharing food and objects) played a major role in influencing how information was transmitted in the group. Some of the most frequent affiliative behaviors were between siblings, thus emphasizing the importance of family ties in learning.

Previous studies have shown that physical proximity between individuals can facilitate learning. However, until now, hardly anything was known about the role of different social connections in observation and learning. To mimic the presence of novel information, the researchers gave raven groups a task with which they were unfamiliar. The task included a food reward to motivate ravens to solve it. Ravens only observed others’ interactions with the task if they had strong social bonds to those group members. Presence of strong social bonds increases tolerance among individuals, allowing them to observe each other from a close distance. Birds with strong bonds to the group members who had already solved the task were able to observe them from a close distance, and as a result, gained this new information sooner than those who were not connected.

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/07/160713101619.htm Original web page at Science Daily

Tags Behaviour (Ethology), Birds (pet; ornamental; prey e.g. falcons), Neurology

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What free will looks like in the brain

Post author By Vetscite
Post date August 10, 2016

Johns Hopkins University researchers are the first to glimpse the human brain making a purely voluntary decision to act.

Unlike most brain studies where scientists watch as people respond to cues or commands, Johns Hopkins researchers found a way to observe people’s brain activity as they made choices entirely on their own. The findings, which pinpoint the parts of the brain involved in decision-making and action, are now online, and due to appear in a special October issue of the journal Attention, Perception, & Psychophysics.

“How do we peek into people’s brains and find out how we make choices entirely on our own?” asked Susan Courtney, a professor of psychological and brain sciences. “What parts of the brain are involved in free choice?”

The team devised a novel experiment to track a person’s focus of attention without using intrusive cues or commands. Participants, positioned in MRI scanners, were left alone to watch a split screen as rapid streams of colorful numbers and letters scrolled past on each side. They were asked simply to pay attention to one side for a while, then to the other side — when to switch sides was entirely up to them. Over an hour, the participants switched their attention from one side to the other dozens of times.

Researchers monitored the participants’ brains as they watched the media stream, both before and after they switched their focus.

For the first time, researchers were able to see both what happens in a human brain the moment a free choice is made, and what happens during the lead-up to that decision — how the brain behaves during the deliberation over whether to act.

The actual switching of attention from one side to the other was closely linked to activity in the parietal lobe, near the back of the brain. The activity leading up to the choice — that is, the period of deliberation — occurred in the frontal cortex, in areas involved in reasoning and movement, and in the basal ganglia, regions deep within the brain that are responsible for a variety of motor control functions including the ability to start an action. The frontal-lobe activity began earlier than it would have if participants had been told to shift attention, clearly demonstrating that the brain was preparing a purely voluntary action rather than merely following an order.

Together, the two brain regions make up the core components underlying the will to act, the authors concluded.

“What’s truly remarkable about this project,” said Leon Gmeindl, a research scientist at Johns Hopkins and lead author of the study, “is that by devising a way to detect brain events that are otherwise invisible — that is, a kind of high-tech ‘mind reading’ — we uncovered important information about what may be the neural underpinnings of volition, or free will.”

Now that scientists have a way to track choices made from free will, they can use the technique to determine what’s happening in the brain as people wrestle with other, more complex decisions. For instance, researchers could observe the brain as someone tried to decide between snacking on a doughnut or on an apple — watching as someone weighed short-term rewards against long-term rewards, and perhaps being able to pinpoint the tipping point between the two.

“We now have the ability to learn more about how we make decisions in the real world,” Courtney said.

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/07/160713114937.htm Original web page at Science Daily

Tags Behaviour (Ethology), Human, Neurology

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* Newborn ducklings can acquire notions of ‘same’ and ‘different’

Post author By Vetscite
Post date August 10, 2016

Scientists from the University of Oxford have shown that newly hatched ducklings can readily acquire the concepts of ‘same’ and ‘different’ — an ability previously known only in highly intelligent animals such as apes, crows and parrots.

Ducklings and other young animals normally learn to identify and follow their mother through a type of learning called imprinting, which can occur in as little as 15 minutes after hatching. Imprinting is a powerful form of learning that can allow ducklings to follow any moving object, provided they see it within the species’ typical ‘sensitive period’ for imprinting.

In this new study, published in the journal Science, ducklings were initially presented with a pair of objects either the same as or different from each other — in shape or in colour — which moved in a circular path.

The ducklings therefore ‘imprinted’ on these pairs of moving objects before being tested for their preferences between different sets of objects. In these subsequent choice tests, each duckling was allowed to follow either of two pairs of objects composed of shapes or colours to which the duckling had not previously been exposed.

For example, if an individual duckling had originally been exposed to a pair of spherical objects, in the choice test it may have had to choose between following a pair of pyramids (same) or a pair made up of one cube and one cuboid (different).

If the birds had learned the relationship between members of the original moving pair, then they should have followed the pairs of novel objects showing that same relationship (either ‘same’ or ‘different’), even if they had never seen the test objects.

In the example above, ducklings that had been imprinted on two spheres should have followed the set of two pyramids, because they were the same as each other. This is exactly what the ducklings did.

About three-quarters of the ducklings preferred to follow the stimulus pair exhibiting the relationship they had learned in imprinting, and their accuracy was as good whether they had to learn the concept of equal or different, or whether they were tested with shapes or colours.

Professor Alex Kacelnik of Oxford University’s Department of Zoology, who has worked extensively on learning and decision-making in animals, said: ‘To our knowledge this is the first demonstration of a non-human organism learning to discriminate between abstract relational concepts without any reinforcement training. The other animals that have demonstrated this ability have all done so by being repeatedly rewarded for correct performance, while our ducklings did it spontaneously, thanks to their predisposition to imprint when very young.

‘And because imprinting happens so quickly, the ducklings learned to discriminate relational concepts much faster than other species, and with a similar level of precision.’

Antone Martinho, a doctoral student in Oxford’s Department of Zoology and the study’s first author, said: ‘While it seems surprising at first that these one-day-old ducklings can learn something that normally only very intelligent species can do, it also makes biological sense. When a duckling is young, it needs to be able to stay near its mother for protection, and an error in identifying her could be fatal.

‘Ducks walk, swim and fly, and are constantly changing their exact shape and appearance as they extend their wings or become partially submerged, or even change angle with respect to the viewer. If the ducklings just had a visual “snapshot” of their mother, they would lose her. They need to be able to flexibly and reliably identify her, and a library of concepts and characteristics describing her is a much more efficient way to do so, compared with a visual memory of every possible configuration of the mother and her environment.

‘Still, this is an unexpected feat for a duckling, and a further reminder that “bird-brain” is quite an unfair slur.’

The discovery of relational concept learning in a new species and in a newly hatched baby bird suggests that this ability may not be as rare or as difficult as previously thought.

Professor Kacelnik added: ‘It may mean that relational concepts are adaptively useful or even necessary to a wider variety of animal. Most animals will, like the ducklings, need identification mechanisms that are robust to natural variation. A challenge we face now is to identify the processes by which the animals’ brains achieve it.’

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/07/160714151856.htm Original web page at Science Daily

Tags Behaviour (Ethology), Birds (pet; ornamental; prey e.g. falcons), Neurology

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Overeating in obese mice linked to altered brain responses to food cues

Post author By Vetscite
Post date August 10, 2016

Obese mice are much more likely than lean mice to overeat in the presence of environmental cues, a behavior that could be related to changes in the brain, finds a new study by a Michigan State University neuroscientist. The study is to be presented this week at the Society for the Study of Ingestive Behavior, the foremost society for research into all aspects of eating and drinking behavior.

The findings offer clues in Alexander Johnson’s quest to unpack the interconnected mechanisms of overeating and obesity. Obesity is an epidemic domestically — more than a third of Americans are considered to be obese — and a growing health problem in other parts of the world.

“In today’s society we are bombarded with signals to eat, from fast-food commercials to the smell of barbecue and burgers, and this likely drives overeating behaviors,” said Johnson, Assistant Professor of Psychology at Michigan State University. “Our study suggests both a psychological and neurobiological account for why obese individuals may be particularly vulnerable to these signals.”

The study involved two groups of mice — one group that was fed a high-calorie diet until they became obese and a second group that was fed a regular lab chow diet so they stayed lean. Johnson then trained the mice with different auditory cues. Whenever they heard one cue, such as a tone, the mice received sugar reward; with a second cue, such as a white noise, they received no reward.

The mice were then given access to their assigned maintenance diet for three days so they were satiated (i.e., not hungry) for the final test phase of the study. In that test, the sugar solution was available to the mice at all times, to see what would trigger them to start eating. When no cue was given, and when the white-noise cue was given (which previously offered no reward), the lean mice and obese mice ate roughly the same amount. When the rewarding tone cue was given, however, the obese mice ate significantly more of the sugar solution compared to the lean mice.

“From a psychological perspective, this tells us that the obese mice are more vulnerable to the effects of environmental triggers on evoking overeating behavior,” Johnson said. “Looking at it through a human lens, this suggests that obese individuals may be more sensitive to overeating food in the presence of say, the McDonald’s Golden Arches.”

Johnson also examined the mice’s lateral hypothalamus, which is known as a key brain area in appetite and feeding behavior. Using a procedure called immunofluorescence to label neurons in this area of the brain, he found that neurons releasing a certain hormone- Melanin-Concentrating Hormone, or MCH — were more abundant in obese mice. But importantly, these MCH-releasing neurons were more active when the obese mice encountered the environmental reminders of sugar.

“In other words, if you become obese this leads to increases in MCH expression, which may make you more sensitive to this form of overeating,” Johnson said.

The novel findings, he added, start to paint a picture of the relationship between brain-behavior mechanisms that may underlie learned overeating in obese individuals.

“This could be one of perhaps many reasons why obese people may have the urge to eat more when presented with food cues.”

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/07/160712092351.htm Original web page at Science Daily

Tags Behaviour (Ethology), Neurology, Rodents/Lags

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*Battling toxoplasmosis: International team describes step-by-step progress

Post author By Vetscite
Post date August 10, 2016

In the July 14 edition of Scientific Reports (Nature), 39 researchers from 14 leading institutions in the United States, United Kingdom and France suggest novel approaches that could hasten the development of better medications for people suffering from toxoplasmosis. This chronic, currently incurable infection, caused by the parasite Toxoplasma gondii, infects the brain and eye of as many as 2 billion people worldwide.

Their findings provide conceptual and practical roadmaps for improving the efficacy and reducing toxicity of available medicines. They also offer insights into the biology of T. gondii, suggest critical molecular targets for new medicines, and offer renewed hope for the speedy development of much-needed curative medicines for those with toxoplasmosis–and potentially malaria.

The researchers describe three significant steps forward: They characterized a new experimental model, a Brazilian strain of T. gondii, called EGS, which behaves in tissue culture much like the dormant cystic parasites that live in human brain cells. This is “an immensely useful and important advance for medicine development,” said the study’s corresponding author Rima McLeod, professor of ophthalmology and visual sciences and of pediatrics at the University of Chicago. “It allows us to define its genotype and phenotype in depth and to identify what it does to its human host’s blood and primary brain stem cells. Remarkably, this encysted parasite turns on host cell pathways in ways that can alter ribosomal function and cause mis-splicing of transcripts as well as other flaws associated with Alzheimer’s and Parkinson’s disease.”

The researchers found targets critical for the parasite’s various life stages. Especially appealing was the parasite’s mitochondrial protein, cytochrome b. The team was able to develop compounds more soluble than existing cytochrome b inhibiting quinolones. These can limit parasite survival, and have physiochemical properties commensurate with crossing the blood-brain barrier to treat central nervous system infections. This work emphasizes that the cytochrome bc 1 complex is a critical target. Co-crystallography of the enzyme with the inhibitor provides information to optimize inhibitory compounds.

They show that greater understanding of T. gondii could have significant implications for anti-malarial research. Compounds they developed were highly effective against Plasmodium falciparum, the parasite that causes malaria, including all tested drug-resistant strains. Malaria, McLeod emphasized, “kills a child every eleven seconds.”

The team’s findings matter because T. gondii is the most frequent cause of infection leading to destruction of the back of the eye for persons in most countries in the world. It is most damaging for infants and children who acquire infection from their mothers during gestation, but it can also cause life-threatening infections in those with compromised immune systems, such as those with cancer, autoimmune disease or AIDS. Highly virulent strains of Toxoplasma are also now known to cause lethal disease, especially in South America.

A large data analysis by researchers at the University of Chicago, published June 26, 2016, in Clinical Infectious Diseases, found that the estimated annual incidence of toxoplasmosis over the last ten years in the US was 6,137 people, based on diagnostic codes for the disease. An editorial in that journal notes that these data “are the strongest to date to indicate that toxoplasmosis represents a significant disease burden in the United States.”

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/07/160715140753.htm Original web page at Science Daily

Tags Human, Neurology, Parasitology

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Human intelligence measured in the brain

Post author By Vetscite
Post date August 10, 2016

Human intelligence is being defined and measured for the first time ever, by researchers at the University of Warwick.

Led by Professor Jianfeng Feng in the Department of Computer Science, studies at Warwick and in China have been recently undertaken to quantify the brain’s dynamic functions, and identify how different parts of the brain interact with each other at different times — namely, to discover how intellect works.

Professor Jianfeng finds that the more variable a brain is, and the more its different parts frequently connect with each other, the higher a person’s IQ and creativity are.

More accurate understanding of human intelligence could lead to future developments in artificial intelligence (AI). Currently, AI systems do not process the variability and adaptability that is vital, as evidenced by Professor Jianfeng’s research, to the human brain for growth and learning. This discovery of dynamic functions inside the brain could be applied to the construction of advanced artificial neural networks for computers, with the ability to learn, grow and adapt.

This study may also have implications for a deeper understanding of another largely misunderstood field: mental health. Altered patterns of variability were observed in the brain’s default network with schizophrenia, autism and Attention Deficit Hyperactivity Disorder (ADHD) patients. Knowing the root cause of mental health defects brings scientists exponentially closer to treating and preventing them in the future.

Using resting-state MRI analysis on thousands of people’s brains around the world, the research has found that the areas of the brain which are associated with learning and development show high levels of variability, meaning that they change their neural connections with other parts of the brain more frequently, over a matter of minutes or seconds. On the other hand, regions of the brain which aren’t associated with intelligence — the visual, auditory, and sensory-motor areas — show small variability and adaptability.

Professor Jianfeng Feng commented that new technology has made it possible to conduct this trail-blazing study: “human intelligence is a widely and hotly debated topic and only recently have advanced brain imaging techniques, such as those used in our current study, given us the opportunity to gain sufficient insights to resolve this and inform developments in artificial intelligence, as well as help establish the basis for understanding and diagnosis of debilitating human mental disorders such as schizophrenia and depression.”

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/07/160718110938.htm Original web page at Science Daily

Tags Human, Neurology

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New discovery on how the inner ear works

Post author By Vetscite
Post date July 26, 2016

Researchers have found that the parts of the inner ear that process sounds such as speech and music seem to work differently than other parts of the inner ear. Researchers from Linköping University are part of the team behind the discovery.

“This helps us understand the mechanisms that enable us to perceive speech and music. We hope that more knowledge about the capabilities of the ear will lead to better treatments for the hearing impaired,” says Anders Fridberger, professor of neuroscience at Linköping University.

To perceive speech and music, you must be able to hear low-frequency sound. And to do this, the brain needs information from the receptors, which are located close to the top of the cochlea, the spiral cavity in the inner ear. This part of the inner ear is difficult to study, as it is embedded in thick bone that is hard to make holes in, without causing damage. Now the international research team has been able to measure, in an intact inner ear, how the hearing organ reacts to sound. The results have been published in PNAS, the Proceedings of the National Academy of Sciences.

To measure in the hearing organ, the researchers used optical coherence tomography, a visualization technology for biological matter that is often used to examine the eye.

“We have been able to measure the inner ear response to sound without having to open the surrounding bone structures and we found that the hearing organ responds in a completely different way to sounds in the voice-frequency range. It goes against what was previously thought of how the inner ear works.

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/07/160711092510.htm Original web page at Science Daily

Tags Anatomy, Human, Neurology

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Current stimulation to the brain partially restores vision in patients with glaucoma and optic nerve damage

Post author By Vetscite
Post date July 26, 2016

Vision loss due to glaucoma or optic nerve damage is generally considered irreversible. Now a new prospective, randomized, multi-center clinical trial demonstrates significant vision improvement in partially blind patients after 10 days of noninvasive, transorbital alternating current stimulation (ACS). In addition to activation of their residual vision, patients also experienced improvement in vision-related quality of life such as acuity, reading, mobility or orientation. The results are reported in PLOS ONE.

“ACS treatment is a safe and effective means to partially restore vision after optic nerve damage probably by modulating brain plasticity, re-synchronizing brain networks, which were desynchronized by vision loss. This class 1 evidence is the first ever large-scale multi-center clinical trial in the field of non-invasive brain modulation using electric currents and suggests that visual fields can be improved in a clinically meaningful way,” commented lead investigator Bernhard A. Sabel, PhD, of the Institute of Medical Psychology, Medical Faculty, Otto-von-Guericke University of Magdeburg (Germany).

In a study conducted at three German clinical centers (University of Göttingen, Charité Berlin, and University of Magdeburg), 82 patients were enrolled in a double-blind, randomized, sham-controlled clinical trial, 33 with visual deficits caused by glaucoma and 32 with anterior ischemic optic neuropathy caused by inflammation, optic nerve compression (due to tumors or intracranial hemorrhage), congenital anomalies, or Leber’s hereditary optic neuropathy. Eight patients had more than one cause of optic nerve atrophy.

The groups were randomized so that 45 patients underwent 10 daily applications of ACS for up to 50 minutes per day over a two-week period and 37 patients received sham stimulation. The only difference between groups before treatment was that the stimulation group included more men than the sham group; no other differences were found, including age of the lesion or visual field characteristics. ACS was applied with electrodes on the skin near the eyes. Vision was tested before and 48 hours after completion of treatment, and then again two months later to check if any changes were long-lasting.

Patients receiving ACS showed significantly greater improvements in perceiving objects in the whole visual field than individuals in the sham-treated group. Specifically, when measuring the visual field, a 24% improvement was noted after treatment in the ACS group compared to a 2.5% improvement in the sham group. This was due to significant improvements in the defective visual field sector of 59% in the ACS group and 34% in the sham group which received a minimal stimulation protocol. Further analyses showed improvements in the ACS group at the edges of the visual field. The benefits of stimulation were found to be stable two months later, as the ACS group showed a 25% improvement in the visual field compared to negligible changes (0.28%) in the sham group.

Patient safety measures were maintained at a high level, in line with previous studies. Current flow was assessed using sophisticated computer simulation models. No participants reported discomfort during stimulation, although temporary dizziness and mild headaches were reported in rare cases.

The study results are in line with previous small sample studies in which efficacy and safety were observed. Those studies revealed that well-synchronized dynamic brain functional networks are critical for vision restoration. Although vision loss leads to de-synchronization, these neural networks can be re-synchronized by ACS via rhythmic firing of the ganglion cells of the retina, activating or “amplifying” residual vision. Dr. Sabel added that “while additional studies are needed to further explore the mechanisms of action, our results warrant the use of ACS treatment in a clinical setting to activate residual vision by brain network re-synchronization. This can partially restore vision in patients with stable vision loss caused by optic nerve damage.”

In summary, vision loss, long considered to be irreversible, can be partially reversed. There is now more light at the end of the tunnel for patients with low vision or blindness following glaucoma and optic nerve damage.

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/06/160629145208.htm Original web page at Science Daily

Tags Human, Neurology, Ophthalmology

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Cerebrovascular disease linked to Alzheimer’s

Post author By Vetscite
Post date July 26, 2016

Study finds association between diseases in brain blood vessels and dementia. While strokes are known to increase risk for dementia, much less is known about diseases of large and small blood vessels in the brain, separate from stroke, and how they relate to dementia. Diseased blood vessels in the brain itself, which commonly is found in elderly people, may contribute more significantly to Alzheimer’s disease dementia than was previously believed, according to new study results published in June in The Lancet Neurology, a British medical journal.

“Cerebral vessel pathology might be an under-recognized risk factor for Alzheimer’s disease dementia,” the researchers wrote.

The study by researchers from the Rush Alzheimer’s Disease Center analyzed medical and pathologic data on 1,143 older individuals who had donated their brains for research upon their deaths, including 478 (42 percent) with Alzheimer’s disease dementia. Analyses of the brains showed that 445 (39 percent) of study participants had moderate to severe atherosclerosis — plaques in the larger arteries at the base of the brain obstructing blood flow — and 401 (35 percent) had brain arteriolosclerosis — in which there is stiffening or hardening of the smaller artery walls.

The study found that the worse the brain vessel diseases, the higher the chance of having dementia, which is usually attributed to Alzheimer’s disease. The increase was 20 to 30 percent for each level of worsening severity. The study also found that atherosclerosis and arteriolosclerosis are associated with lower levels of thinking abilities, including in memory and other thinking skills, and these associations were present in persons with and without dementia.

“Both large and small vessel diseases have effects on dementia and thinking abilities, independently of one another, and independently of the common causes of dementia such as Alzheimer’s pathology and strokes,” said Dr. Zoe Arvanitakis. A neurologist and researcher at the Rush Alzheimer’s Disease Center, Arvanitakis led the study, which was funded by the National Institutes of Health.

Part of Rush University Medical Center, the Rush Alzheimer’s Disease Center is dedicated to the study of Alzheimer’s, a neurological condition that is the most common cause of dementia. It is one of 29 designated centers in the United States funded by the National Institute on Aging.

The study was not designed to determine causation of Alzheimer’s dementia, or even whether vascular disease or Alzheimer’s developed first. “But it does suggest that vessel disease plays a role in dementia,” Arvanitakis said. “We found that blood vessel diseases are very common in the brain, and are associated with dementia that is typically attributed to Alzheimer’s disease during life.”

Does preventing cerebrovascular disease also prevent Alzheimer’s?

The study examined which cognitive difficulties are caused by vessel diseases and whether vessel disease and Alzheimer’s are more destructive in tandem than they would be alone. An editorial in The Lancet Neurology that accompanied the study findings noted that while other studies have indicated that proactive measures like eating a selective diet and getting regular exercise might protect people against getting Alzheimer’s, those interventions might actually be acting on non-Alzheimer’s disease processes, such as cerebrovascular disease.

Arvanitakis says they don’t know yet. “They may decrease actual Alzheimer’s, and possibly even work by yet other pathways,” Arvanitakis said. “We hope to better distinguish how the clinical expression of vessel diseases in the brain differ from those of Alzheimer’s, so that we may eventually use earlier and more targeted treatments for dementia.”

Nearly 47 million people now live with dementia worldwide, according Alzheimer’s Disease International, the international federation of Alzheimer associations around the world. By 2050, that number is projected to be 132 million. Therefore, finding ways to treat or prevent the disease “is a major goal,” Arvanitakis said.

The participants in the study published in Lancet Neurology came from two (RADC) cohort studies, the Religious Orders Study and the Rush Memory and Aging Project, which have followed people older than 65, in their communities, for more than two decades. Participants receive annual health assessments and agree to donate their brains for research upon their deaths. The Lancet Neurology study used clinical data gathered from participants from 1994 to 2015, and pathologic data obtained from examination of the brains donated for autopsy, and used regression analyses to determine the odds of Alzheimer’s dementia and levels of cognitive function, for increasing levels of brain vessel diseases.

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/07/160701183319.htm Original web page at Science Daily

Tags Human, Neurology

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Copper-induced misfolding of prion proteins

Post author By Vetscite
Post date July 26, 2016

Iowa State University researchers have described with single-molecule precision how copper ions cause prion proteins to misfold and seed the misfolding and clumping of nearby prion proteins.

The researchers also found the copper-induced misfolding and clumping is associated with inflammation and damage to nerve cells in brain tissue from a mouse model.

Prions are abnormal, pathogenic agents that are transmissible and induce abnormal folding of a specific type of protein called prion proteins, according to the Centers for Disease Control and Prevention. Prion proteins are mostly found in the brain. The abnormal folding of prion proteins leads to brain damage and symptoms of neurodegenerative disease. A similar cycle of neuronal protein misfolding and clumping is observed in other neurodegenerative disorders, including Parkinson’s and Alzheimer’s diseases.

“Our study establishes a direct link, at the molecular level, between copper exposure and prion protein neurotoxicity,” the researchers wrote in a summary of the paper.

The findings were published today in the journal Science Advances. The corresponding author is Sanjeevi Sivasankar, an Iowa State University associate professor of physics and astronomy; the first author is Chi-Fu Yen, an Iowa State doctoral student in electrical and computer engineering. Co-authors are Anumantha Kanthasamy, an Iowa State Clarence Hartley Covault Distinguished Professor in Veterinary Medicine, chair of biomedical sciences and director of the Iowa Center for Advanced Neurotoxicology; and Dilshan Harischandra, an Iowa State doctoral student in biomedical sciences.

Grants from the National Institute of Environmental Health Sciences at the National Institutes of Health supported the project, including one from the Virtual Consortium for Transdisciplinary Environmental Research.

Although this study determined that copper-induced misfolding and clumping of prion proteins is associated with the degeneration of nerve tissues, Sivasankar cautioned that the study does not directly address the infectivity of prion diseases.

“There are different strains of misfolded prion proteins and not all of them are pathogenic,” Sivasankar said. “Although we do not show that the strains generated in our experiments are infectious, we do prove that copper ions trigger misfolding of prion proteins which causes toxicity in nerve cells.”

The Sivasankar and Kanthasamy research groups plan to perform additional studies to determine if the copper-induced misfolding causes disease.

Integrating approaches Sivasankar also noted that a unique aspect of this project was the integration of biophysical and neurotoxicological research approaches. He said the combination has the potential to transform studies of the molecular basis for neurodegenerative diseases.

A fluorescence-based technique that identified misfolded prion proteins with single-molecule sensitivity and determined the role of metal ions in misfolding. The researchers used this technique to show that misfolding begins when copper ions bind to the unstructured tail of the prion protein. A single-molecule atomic force microscopy assay that measured the efficiency of prion protein clumping. The researchers used this technique to show that misfolded prion proteins stick together nearly 900 times more efficiently than properly folded proteins.

The Kanthasamy and Sivasankar research groups worked together on a real-time, quaking-induced conversion assay to demonstrate that misfolded prion proteins serve as seeds that trigger the misfolding and clumping of nearby prion proteins. Kanthasamy’s research group also used its expertise in neurotoxicology to show the copper-induced, misfolded prion proteins damage nerve cells in slices of brain tissue from mice.

Taken together, the results identify the biophysical conditions and mechanisms for copper-induced prion protein misfolding, clumping and neurotoxicity, the researchers wrote.

“This was a very comprehensive study,” Sivasankar said. “We took it from single molecules all the way to tissues.”

And, although the study doesn’t address the infectious nature of prion diseases, Kanthasamy said it is still important: “This study has major implications to our understanding the role of metals in protein misfolding diseases including prion, Alzheimer’s and Parkinson’s diseases.”

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/07/160701183556.htm Original web page at Science Daily

Tags Biochemistry, Neurology, Rodents/Lags

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The relentless dynamism of the adult brain

Post author By Vetscite
Post date July 26, 2016

Scientists from the Institut Pasteur and the CNRS were able to make real-time observations over a period of several months that reveal how new adult-born neurons are formed and evolve in the olfactory bulb of mice. They made the surprising discovery that there is constant structural plasticity in the connections established by these new neurons with the circuits into which they are recruited. The scientists showed that this neuronal dynamism can enable optimal processing of sensory information by the olfactory bulb. These findings are to be published in the journal Neuron on June 30, 2016.

Although most neurons are generated during embryogenesis, some regions of the brain, such as the olfactory bulb in rodents and the hippocampus in humans, are capable of constantly regenerating their neurons in adulthood. Scientists first conclusively discovered these new adult neurons around 15 years ago, but their function remained a mystery, mainly because they are inaccessible in living animals.

In an article published in the journal Neuron, scientists from a unit at the Institut Pasteur directed by CNRS scientist Pierre-Marie Lledo provide further evidence of the highly dynamic nature of the changes observed at the neuronal level in adult brains. The scientists spent several months observing the development of neurons formed in adulthood in the olfactory bulbs of mice. This gave them the unique opportunity to see the formation, stabilization and elimination of connections between neurons in real time.

They revealed that in the olfactory bulb, where new neurons are continuously formed, the connections between these new neurons and neighboring cells are significantly rearranged throughout their lifetime. All these neurons are constantly reorganizing the billions of “synaptic” contacts they establish among themselves. The scientists were surprised by this observation. “We expected to see the synapses gradually stabilizing, as happens during brain development. But astonishingly, these synapses proved to be highly dynamic throughout the life of the new neurons. Also, these dynamics were reflected in the principal neurons, their primary synaptic partner,” explained first author, Kurt Sailor, from the Institut Pasteur.

To observe the ongoing formation of neuronal circuits, the scientists marked the new neurons with a green fluorescent protein (GFP), to allow imaging of the dynamic changes with microscopy. These experiments were carried out over a period of several months to follow the entire life cycle of the new neurons. In the first three weeks of their life, these new neurons extended their cellular projections, known as dendrites, to form several ramifications, which subsequently became very stable. They next observed the neuronal spines, the structure where synapses form, and demonstrated that 20% of the synapses between new and pre-existing neurons were changed on a daily basis — a phenomenon that was also observed in their synaptic partners, the principal olfactory bulb neurons. Using computer-based models, the authors showed that these dynamics enabled the synaptic network to adjust efficiently and reliably to ongoing sensory changes in the environment.

“Our findings suggest that the plasticity of this constantly regenerating region of the brain occurs with continuous physical formation and elimination of synaptic connections. This structural plasticity reveals a unique dynamic mechanism that is vital for the regeneration and integration of new neurons within the adult brain circuit,” concluded the scientists. More generally, this study suggests a universal plasticity mechanism in brain regions that are closely associated with memory and learning.

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/07/160701120520.htm Original web page at Science Daily

Tags Cell Biology, Neurology, Rodents/Lags

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* The story of how a touch screen helped a paralyzed chimp walk again

Post author By Vetscite
Post date July 26, 2016

The case of Reo, a male chimpanzee that learned to walk again after being paralyzed due to illness, shows how much can be done to rehabilitate animals injured in captivity. So says lead author Yoko Sakuraba of Kyoto University, in an article in Primates, the official journal of the Japan Monkey Centre published by Springer.

In their normal work, researchers of the Primate Research Institute at Kyoto University use chimpanzees’ interaction with computers and touch screens to study the cognition and perception of these primates. When Reo was paralyzed from the neck down, dedicated staff put this technology to further use by encouraging the animal to walk again. This is the first case in which a paralyzed chimpanzee has been rehabilitated through such a dedicated programme.

When Reo was 24 years old in 2006, he suddenly became paralyzed when a portion of his spinal cord became inflamed. For the first ten months thereafter, the chimpanzee was severely disabled, lying on his back. He gradually recovered enough to sit up, and could later pull himself upright by using suspended ropes. Intensive physiotherapy over a period of 41 months followed, after which he was able to climb about again using only his arms.

To aid Reo’s ultimate integration back among the other twelve animals held at the institute, his carers decided to try to get him walking again. They incorporate a computerised task in this process. This was considered an option because in his youth Reo had learnt how to perform cognitive tasks on a touch panel, and in so doing had become used to receiving food rewards whenever he succeeded at tasks presented to him.

A computer-controlled monitor was therefore placed on one wall, and cognitive tasks were again put to him. It was not plain sailing at first, and the research team had to adapt their ideas seven times before they received any cooperation from a somewhat fearful Reo. Thereafter, whenever he completed a task successfully, a food reward was placed on a tray on the opposite side of the room. This meant that Reo had to move at least two meters to reach it. To busy himself at the screen again to start a new task, he had to make the two meter return journey.

At first he did so using a rope for assistance, but gradually he started travelling in an upright seated position which resembled the side-to-side manner of a penguin walking on land. The rehabilitation sessions encouraged him to increase his movements considerably, and he started walking up to five hundred meters in a two-hour session.

“Cognitive tasks may be a useful way to rehabilitate physically disabled chimpanzees, and thus improve their welfare in captivity,” says Sakuraba, who says that euthanasia need not be the only option for animals injured in captivity.

She further notes that the personality and physical condition of each animal must be considered when designing and adjusting such a rehabilitation program.

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/07/160705120143.htm Original web page at Science Daily

Tags Behaviour (Ethology), Neurology, Primates

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A sense of direction in the brain: Seeing the inner compass

Post author By Vetscite
Post date July 26, 2016

A team of neuroscientists led by Dr. Andrea Burgalossi of the Tübingen Werner Reichardt Centre for Integrative Neuroscience (CIN) at the University of Tübingen has taken an important step towards understanding the ‘inner compass’. Investigating so-called head direction cells (HD cells) in the rodent brain, they were able to find evidence of networks that had been purely theoretical for more than a decade: HD cells are directly linked with different types of brain structures that control navigation. Most intriguingly, they forward information to areas known to contain grid cells — a cell type considered very important in keeping track of one’s position in one’s surroundings, much like a GPS system.

“It was extremely exciting to actually see these cells and their connections under the microscope for the first time,” says Dr. Burgalossi. “They had been a scientific ghost for such a long time.” The cells whose discovery so elates the Tübingen neuroscientist are called HD cells. Their existence was stipulated in the early 1990s, including their function: HD cells recognise the head’s current angle and facing, a simple yet essential part of recognising one’s place in space, and thus of navigation.

But until now, HD cells and their connections with other brain areas had not been identified and observed. The Tübingen researchers were the first to successfully identify them in rats’ brains and observe them microscopically. The researchers found their target by inserting hair-thin glass electrodes into the presubiculum, a brain area that had been previously shown to contain HD cells. These electrodes detected the small electrical impulses in the cell they were attached to, generated whenever the rat was facing a particular direction. The presubiculum consists of several layers, which contain different types of neurons. Not all of them are HD cells. “HD cells have a specific morphology and are predominantly found in layer 3 of the presubiculum. We found no HD cells in layer 2, where the neurons also look different,” Burgalossi explains, “now we have proven that there is a strong relationship between structure and function.” This structure-function relationship can be considered the holy grail of neuroscience, as it allows researchers to not only say ‘this part of the brain does that’, but also lets them gain insights into how the individual neurons do their job.

Moreover, the researchers’ work provides the first piece of evidence that could explain how HD cells forward information from the presubiculum to other brain areas concerned with navigation. In the brain, networks are formed by axons, long and extremely thin appendages that allow neurons to connect to each other. Axons are the ‘wiring’ that makes up the brain’s ‘circuitry’. They can grow to several millimeters in length even in the tiny brains of rodents, while being only about one micrometer in diameter. These dimensions are also the reason why it is so hard to collect direct evidence of network connections between brain structures. Identifying individual neurons under the microscope is done by injecting dyes into the cell body. But neurons are so thin and their axons can be so long that this is no guarantee one actually gets to see one: “The difficult part of our job is often the labeling procedures” says Burgalossi. “Only if you can efficiently fill a HD cell with dye will you be able to find out which specific neuron — among the many different types in the brain — you have before you, and discover where it projects.”

The team found that HD cells in the presubiculum feed information into the medial entorhinal cortex (MEC), a brain area attracting much attention in neuroscience: this is where the fabled ‘grid cells’ are located, a recently discovered type of neuron that got its name from the way its activity forms a very regular ‘grid-map’ of the environment. The discovery of grid cells earned the Norwegian scientist couple Edvard and May-Britt Moser the Nobel Prize in Physiology or Medicine in 2014. The Tübingen neuroscientists’ new results provide the first anatomical evidence of how the entorhinal grid cell area might be functionally connected to the rest of the brain’s navigational apparatus, in particular with HD cells. Neuroscience is one step closer to understanding the inner compass now.

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/07/160706092801.htm Original web page at Science Daily

Tags Neurology, Rodents/Lags

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* Imaging study in mice sheds light on how the brain draws a map to a destination

Post author By Vetscite
Post date July 26, 2016

Columbia scientists have uncovered a key feature of the brain’s GPS that helps a mouse find what it is seeking. The study enabled scientists to define the precise duties of cells in a particular region of the hippocampus, the brain’s learning and memory center. The research also advances a long-standing quest in the field of neuroscience: tracing the pathway that information takes while traveling through the brain.

The authors announced these findings in the journal Neuron. “In this study, our goal was to simulate what our brains do as we walk aimlessly down the street, versus how our brains behave when looking for a specific address,” said Attila Losonczy, MD, PhD, a principal investigator at Columbia’s Mortimer B. Zuckerman Mind Brain Behavior Institute, associate professor of neuroscience at Columbia University Medical Center (CUMC) and the paper’s senior author. “By using the powerful two-photon microscope, we were able to observe the activity of individual cells in the mouse hippocampus, and then link that activity to a specific behavior — in this case, navigation — a technological feat that would have been impossible just a few years ago.”

The hippocampus can be divided into distinct areas that form an interconnected circuit through which memory-related information is processed. For this study, Dr. Losonczy and his team focused on the hippocampus’ main output node, area CA1, which was discovered by scientists to encode one’s location — work that was awarded the 2014 Nobel Prize.

“We’ve known that CA1 can be divided into two distinct sublayers of cells: the deep and superficial sublayers,” said Nathan Danielson, a doctoral candidate in neuroscience at CUMC and the paper’s first author. “Scientists have wondered whether this division was an indication that these two sublayers actually served different purposes in learning and memory. But no one had tested it, so we decided to look.”

To study these cells, the researchers placed mice on treadmills that had distinct colors, textures and smells while a two-photon microscope monitored the cellular activity in the CA1. The mice then performed two tasks.

In the first, mice ran on a treadmill while experiencing different sights and sounds, some familiar and others new. In the second, mice were given the task of finding a water reward placed at a specific, unmarked location along the treadmill. The team repeated these experiments over the course of several sessions and monitored how each of the sublayers responded to the different types of learning.

When the mice performed the first task, cells in the superficial sublayer of CA1 appeared to create an internal map that remained largely unchanged from session to session. By contrast, cells in the deep sublayer formed an internal map that was far more dynamic — in effect redrawing a different version of the map during each session.

During the second task, however, when the mice needed to learn the location of the hidden reward, the maps in the deep sublayer were significantly more stable, and less dynamic, than in the first task. The scientists also found that deep-sublayer activity was closely linked to the animal’s ability to find the reward. This distinction between the sublayers, the authors argue, could signify two different processes important for navigation.

“If you’re walking down the street looking for something specific — say, your favorite restaurant — your brain first needs a map of the neighborhood in general,” said Danielson. But to find that particular restaurant, he continued, the brain also assigns importance, or salience, to that specific location.

“In a sense, it’s the brain’s way of marking a location on a map with a giant X,” Danielson said. “So as you look for that restaurant, you need both the map and the X. Our findings suggest that, in the brain, these distinct types of information could be conveyed by the CA1’s distinct sublayers.”

“And if one month later you wanted to visit somewhere new, the deep sublayer would update the map, effectively marking the spot of the new location, while the underlying map of the neighborhood, created by the superficial sublayer, would remain relatively unchanged,” added Dr. Losonczy.

For Dr. Losonczy, this study speaks to the ingenious way that the brain’s underlying architecture allows it to accomplish a specific type of navigation.

“It’s astounding that the ability to navigate to a desired location, an enormously complex feat, can be represented so precisely in the structure of the hippocampus,” he said. “And it’s even more astounding that we can now witness it happening in real time.”

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/07/160707131127.htm Original web page at Science Daily

Tags Cell Biology, Neurology, Rodents/Lags

News

Cats seem to grasp the laws of physics

Post author By Vetscite
Post date July 12, 2016

Cats understand the principle of cause and effect as well as some elements of physics. Combining these abilities with their keen sense of hearing, they can predict where possible prey hides. These are the findings of researchers from Kyoto University in Japan, led by Saho Takagi and published in Springer’s journal Animal Cognition.

Previous work conducted by the Japanese team established that cats predict the presence of invisible objects based on what they hear. In the present study, the researchers wanted to find out if cats use a causal rule to infer if a container holds an object, based on whether it is shaken along with a sound or not. The team also wanted to establish if cats expect an object to fall out or not, once the container is turned over.

Thirty domestic cats were videotaped while an experimenter shook a container. In some cases this action went along with a rattling sound. In others it did not, to simulate that the vessel was empty. After the shaking phase, the container was turned over, either with an object dropping down or not.

Two experimental conditions were congruent with physical laws, where shaking was accompanied by a (no) sound and an (no) object to fall out of the container. The other two conditions were incongruent to the laws of physics. Either a rattling sound was followed by no object dropping out of the container or no sound while shaking led to a falling object.

The cats looked longer at the containers which were shaken together with a noise. This suggests that cats used a physical law to infer the existence (or absence) of objects based on whether they heard a rattle (or not). This helped them predict whether an object would appear (or not) once the container was overturned.

The animals also stared longer at containers in incongruent conditions, meaning an object dropped despite its having been shaken noiselessly or the other way around. It is as if the cats realized that such conditions did not fit into their grasp of causal logic.

“Cats use a causal-logical understanding of noise or sounds to predict the appearance of invisible objects,” says Takagi.

Researchers suggest that species’ surroundings influence their ability to find out information based on what they hear. The ecology of cats’ natural hunting style may therefore also favor the ability for inference on the basis of sounds. Takagi explains that hunting cats often need to infer the location or the distance of their prey from sounds alone because they stake out places of poor visibility. Further research is needed to find out exactly what cats see in their mind’s eye when they pick up noises, and if they can extract information such as quantity and size from what they hear.

https://www.sciencedaily.com/ Science Daily

https://www.sciencedaily.com/releases/2016/06/160614114410.htm Original web page at Science Daily

Tags Biotechnology (Ethics), Cats, Neurology