Posts tagged neuron

July 31, 2012

Wayne State University School of Medicine researchers, working with colleagues in Canada, have found that one or more substances produced by a type of immune cell in people with multiple sclerosis (MS) may play a role in the disease’s progression. The finding could lead to new targeted therapies for MS treatment.

B cells, said Robert Lisak, M.D., professor of neurology at Wayne State and lead author of the study, are a subset of lymphocytes (a type of circulating white blood cell) that mature to become plasma cells and produce immunoglobulins, proteins that serve as antibodies. The B cells appear to have other functions, including helping to regulate other lymphocytes, particularly T cells, and helping maintain normal immune function when healthy.

In patients with MS, the B cells appear to attack the brain and spinal cord, possibly because there are substances produced in the nervous system and the meninges — the covering of the brain and spinal cord — that attract them. Once within the meninges or central nervous system, Lisak said, the activated B cells secrete one or more substances that do not seem to be immunoglobulins but that damage oligodendrocytes, the cells that produce a protective substance called myelin.

The B cells appear to be more active in patients with MS, which may explain why they produce these toxic substances and, in part, why they are attracted to the meninges and the nervous system.

The brain, for the most part, can be divided into gray and white areas. Neurons are located in the gray area, and the white parts are where neurons send their axons — similar to electrical cables carrying messages — to communicate with other neurons and bring messages from the brain to the muscles. The white parts of the brain are white because oligodendrocytes make myelin, a cholesterol-rich membrane that coats the axons. The myelin’s function is to insulate the axons, akin to the plastic coating on an electrical cable. In addition, the myelin speeds communication along axons and makes that communication more reliable. When the myelin coating is attacked and degraded, impulses — messages from the brain to other parts of the body — can “leak” and be derailed from their target. Oligodendrocytes also seem to engage in other activities important to nerve cells and their axons. 

The researchers took B cells from the blood of seven patients with relapsing-remitting MS and from four healthy patients. They grew the cells in a medium, and after removing the cells from the culture collected material produced by the cells. After adding the material produced by the B cells, including the cells that produce myelin, to the brain cells of animal models, the scientists found significantly more oligodendrocytes from the MS group died when compared to material produced by the B cells from the healthy control group. The team also found differences in other brain cells that interact with oligodendrocytes in the brain.

"We think this is a very significant finding, particularly for the damage to the cerebral cortex seen in patients with MS, because those areas seem to be damaged by material spreading into the brain from the meninges, which are rich in B cells adjacent to the areas of brain damage," Lisak said.

The team is now applying for grants from several sources to conduct further studies to identify the toxic factor or factors produced by B cells responsible for killing oligodendrocytes. Identification of the substance could lead to new therapeutic methods that could switch off the oligodendrocyte-killing capabilities of B cells, which, in turn, would help protect myelin from attacks.

Provided by Wayne State University

Source: medicalxpress.com

July 27, 2012 

(Medical Xpress) — Johns Hopkins scientists have discovered a “scaffolding” protein that holds together multiple elements in a complex system responsible for regulating pain, mental illnesses and other complex neurological problems.

Preso1 (green) and mGluR5 (red) appear in the same location inside a neuron.

The finding, published in the May 6 issue of Nature Neuroscience, could give researchers a new target for drugs to treat these often-intractable conditions.

The discovery, detailed in a study led by neuroscience professor Paul Worley, M.D., of the Johns Hopkins University School of Medicine, focuses on a family of proteins called group 1 metabotropic glutamate receptors (mGluRs) that lie on the surfaces of nerve cells. When these receptors lock in glutamate, a chemical that neurons use to communicate, it encourages neurons to fire.

Without a way to turn off these receptors, neurons would remain active indefinitely, keeping pain and other responses going long after they’re useful. Previous research suggested that these mGluRs need to bind to another protein called Homer to shut down, and that this binding is stronger after other molecules called protein kinases modify the receptors. However, Worley explains, thus far it’s been unclear exactly how all these different players come together.

Seeking the mechanism behind this phenomenon, Worley and his colleagues started with a series of experiments to see what other proteins the mGluRs and Homer were binding with in rat brains. Their search turned up a third protein called Preso1, which bound to both mGluRs and Homer. A search in genetic databases shows that the gene responsible for making Preso1 is present in animals ranging from fruit flies to people, highlighting its importance in a wide variety of creatures.

To figure out what Preso1 does, the researchers performed another series of experiments to examine behavior of neurons that produced both mGluRs and Homer. They found that when these neurons also expressed Preso1, the mGluRs bound Homer more efficiently, suggesting that Preso1 might somehow increase modification by protein kinases.

Worley’s team received another clue when they found that protein kinases also bind to Preso1.

Genetically modifying mice so that they don’t make any Preso1, the researchers found that binding between mGluRs and Homer in these animals’ neurons was greatly reduced compared to normal mice.

Additionally, when the researchers injected the modified mice with a chemical that causes pain and inflammation, the animals had a significantly greater and longer-lasting response compared to regular mice. A final experiment showed that neurons taken from the modified animals were significantly more responsive to the neurotransmitter glutamate. When the researchers added Preso1 to the cell cultures, this increased activity disappeared, suggesting that Preso1 is pivotal for mGluRs to signal properly.

Taken together, Worley explains, the findings suggest that Preso1 appears to gather all the important elements in this system — Homer, protein kinases and mGluRs — bringing them all together to coordinate the activation and deactivation of the mGluRs.

With Preso1 so pivotal for regulating group 1 mGluR activity, it could prove a useful new target for drugs to treat a variety of health problems in which these receptors are thought to play a role, including chronic pain, schizophrenia, Alzheimer’s disease, and fragile X syndrome, Worley says.

"Because mGluRs play so many important roles in the brain for so many different mental and neurological health conditions, knowledge of their regulatory mechanisms is extremely important. But we really don’t know how they work in great detail," he says. "You need to know all the players before you can understand the system. Here, we’ve identified an important player that no one had previously known had existed. Preso1 and Homer appear essential for desensitization of mGluR signaling, much like beta-adrenergic receptor kinase and arrestin are important for desensitization of adrenergic and opiate receptors."

Provided by Johns Hopkins University

Source: medicalxpress.com

July 26, 2012

Excitation of neurons depends on the selected influx of certain ions, namely sodium, calcium and potassium through specific channels. Obviously, these channels were crucial for the evolution of nervous systems in animals. How such channels could have evolved their selectivity has been a puzzle until now. Yehu Moran and Ulrich Technau from the University of Vienna together with Scientists from Tel Aviv University and the Woods Hole Oceanographic Institution (USA) have now revealed that voltage-gated sodium channels, which are responsible for neuronal signaling in the nerves of animals, evolved twice in higher and lower animals. These results were published in Cell Reports.

Close-up of nervous system of a transgenic polyp of the sea anemone Nematostella vectensis, in which a red fluorescent reporter gene (mCherry) is driven by the regulatory sequence of the neuronal ELAV gene. The picture shows the diffuse structure of the nervous system, but also reveals the accumulation of longitudinal axonal tracts along the eight gastric tissue folds (mesenteries). Credit: Copyright: U. Technau

The opening and closing of ion channels enable flow of ions that constitute the electrical signaling in all nervous systems. Every thought we have or every move we make is the result of the highly accurate opening and closing of numerous ion channels. Whereas the channels of most lower animals and their unicellular relatives cannot discern between sodium and calcium ions, those of higher animals are highly specific for sodium, a characteristic that is important for fast and accurate signaling in complex nervous system.

Surprising results in sea anemones and jellyfish

However, the researchers found that a group of basal animals with simple nerve nets including sea anemones and jellyfish also possess voltage-gated sodium channels, which differ from those found in higher animals, yet show the same selectivity for sodium. Since cnidarians separated from the rest of the animals more than 600 million years ago, these findings suggest that the channels of both cnidarians and higher animals originated independently twice, from ancient non-selective channels which also transmit calcium.

Since many other processes of internal cell signaling are highly dependent on calcium ions, the use of non-selective ion channels in neurons would accidently trigger various signaling systems inside the cells and will cause damage. The evolution of selectivity for sodium ions is therefore considered as an important step in the evolution of nervous systems with fast transmission. This study shows that different parts of the channel changed in a convergent manner during the evolution of cnidarians and higher animals in order to perform the same task, namely to select for sodium ions.

This demonstrates that important components for the functional nervous systems evolved twice in basal and higher animals, which suggests that more complex nervous systems that rely on such ion-selective channels could have also evolved twice independently.

Source: PHYS.ORG

ScienceDaily (July 26, 2012) — Researchers reporting online on July 26 in Current Biology, a Cell Press publication, have for the first time shown that they can control the behavior of monkeys by using pulses of blue light to very specifically activate particular brain cells. The findings represent a key advance for optogenetics, a state-of-the-art method for making causal connections between brain activity and behavior. Based on the discovery, the researchers say that similar light-based mind control could likely also be made to work in humans for therapeutic ends.

(Credit: © Eric Isselée / Fotolia)

"We are the first to show that optogenetics can alter the behavior of monkeys," says Wim Vanduffel of Massachusetts General Hospital and KU Leuven Medical School. "This opens the door to use of optogenetics at a large scale in primate research and to start developing optogenetic-based therapies for humans."

In optogenetics, neurons are made to respond to light through the insertion of light-sensitive genes derived from particular microbial organisms. Earlier studies had primarily validated this method for use in invertebrates and rodents, with only a few studies showing that optogenetics can alter activity in monkey brains on a fine scale.

In the new study, the researchers focused on neurons that control particular eye movements. Using optogenetics together with functional magnetic resonance imaging (fMRI), they showed that they could use light to activate these neurons, generating brain activity and subtle changes in eye-movement behavior.

The researchers also found that optogenetic stimulation of their focal brain region produced changes in the activity of specific neural networks located at some distance from the primary site of light activation.

The findings not only pave the way for a much more detailed understanding of how different parts of the brain control behavior, but they may also have important clinical applications in treating Parkinson’s disease, addiction, depression, obsessive-compulsive disorder, and other neurological conditions.

"Several neurological disorders can be attributed to the malfunctioning of specific cell types in very specific brain regions," Vanduffel says. "As already suggested by one of the leading researchers in optogenetics, Karl Deisseroth from Stanford University, it is important to identify the underlying neuronal circuits and the precise nature of the aberrations that lead to the neurological disorders and potentially to manipulate those malfunctioning circuits with high precision to restore them. The beauty of optogenetics is that, unlike any other method, one can affect the activity of very specific cell types, leaving others untouched."

Source: Science Daily

July 25, 2012

(Medical Xpress) — New understanding of how the brain processes information from inner ear offers hope for sufferers of vertigo.

If you have ever looked over the edge of a cliff and felt dizzy, you understand the challenges faced by people who suffer from symptoms of vestibular dysfunction such as vertigo and dizziness. There are over 70 million of them in North America. For people with vestibular loss, performing basic daily living activities that we take for granted (e.g. dressing, eating, getting in and out of bed, getting around inside as well as outside the home) becomes difficult since even small head movements are accompanied by dizziness and the risk of falling.

We’ve known for a while that a sensory system in the inner ear (the vestibular system) is responsible for helping us keep our balance by giving us a stable visual field as we move around. And while researchers have already developed a basic understanding of how the brain constructs our perceptions of ourselves in motion, until now no one has understood the crucial step by which the neurons in the brain select the information needed to keep us in balance.

The way that the brain takes in and decodes information sent by neurons in the inner ear is complex. The peripheral vestibular sensory neurons in the inner ear take in the time varying acceleration and velocity stimuli caused by our movement in the outside world (such as those experienced while riding in a car that moves from a stationary position to 50 km per hour). These neurons transmit detailed information about these stimuli to the brain (i.e. information that allows one to reconstruct how these stimuli vary over time) in the form of nerve impulses.

Scientists had previously believed that the brain decoded this information linearly and therefore actually attempted to reconstruct the time course of velocity and acceleration stimuli. But by combining electrophysiological and computational approaches, Kathleen Cullen and Maurice Chacron, two professors in McGill University’s Department of Physiology, have been able to show for the first time that the neurons in the vestibular nuclei in the brain instead decode incoming information nonlinearly as they respond preferentially to unexpected, sudden changes in stimuli.

It is known that representations of the outside world change at each stage in this sensory pathway. For example, in the visual system neurons located closer to the periphery of the sensory system (e.g. ganglion cells in the retina) tend to respond to a wide range of sensory stimuli (a “dense” code), whereas central neurons (e.g. in the primary visual cortex at the back of the head tend to respond much more selectively (a “sparse” code). Chacron and Cullen have discovered that the selective transmission of vestibular information they were able to document for the first time occurs as early as the first synapse in the brain. “We were able to show that the brain has developed this very sophisticated computational strategy to represent sudden changes in movement in order to generate quick accurate responses and maintain balance,” explained Prof. Cullen. “I keep describing it as elegant, because that’s really how it strikes me.”

This kind of selectivity in response is important for everyday life, since it enhances the brain’s perception of sudden changes in body posture. So that if you step off an unseen curb, within milliseconds, your brain has both received the essential information and performed the sophisticated computation needed to help you readjust your position. This discovery is expected to apply to other sensory systems and eventually to the development of better treatments for patients who suffer from vertigo, dizziness, and disorientation during their daily activities. It should also lead to treatments that will help alleviate the symptoms that accompany motion and/or space sickness produced in more challenging environments.

Provided by McGill University

Source: medicalxpress.com

July 23, 2012

Mice appear to have a specialized system for detecting and at least initially processing instinctually important smells such as those that denote predators. The finding raises a question about whether their response to those smells is hardwired.

A separate subsystem for the smell of fear. Experiments in mice suggest neurons that detect odors associated with an instinctive response — like fleeing when an approaching predator is detected — are configured differently than other olfactory neurons. Further research could determine whether this system automatically triggers flight or other primal behaviors.Credit: Mike Cohea/Brown University

PROVIDENCE, R.I. [Brown University] — A new study finds that mice have a distinct neural subsystem that links the nose to the brain and is associated with instinctually important smells such as those emitted by predators. That insight, published online this week in Proceedings of the National Academy of Sciences, prompts the question whether mice and other mammals have specially hardwired neural circuitry to trigger instinctive behavior in response to certain smells.

In the series of experiments and observations described in the paper, the authors found that nerve cells in the nose that express members of the gene family of trace amine-associated receptors (TAAR) have several key biological differences from the much more common and diverse neurons that express members of the olfactory receptor gene family. Those other nerve cells detect a much broader range of smells, said corresponding author Gilad Barnea, the Robert and Nancy Carney Assistant Professor of Neuroscience at Brown University.

The differences between TAAR neurons and olfactory receptor neurons led Barnea and his co-authors to conclude that they form an independent subsystem for certain smells.

“Our observations suggest that the TAAR-expressing sensory neurons constitute a distinct olfactory subsystem that extracts specific environmental cues that then elicit innate responses,” Barnea said.

Read more …

19 July 2012 by Nicola Guttridge

Whether a tree branch or a computer mouse is the target, reaching for objects is fundamental primate behaviour. Neurons in the brain prepare for such movements, and this neural activity can now be deciphered, allowing researchers to predict what movements will occur. This discovery could help us develop prosthetic limbs that can be controlled by thought alone.

What happens next? (Image: Gallo Images/Rex Features)

To find out what goes on in the brain when we reach for things, biomedical engineers Daniel Moran and Thomas Pearce at Washington University in St Louis, Missouri, trained two rhesus macaques to participate in a series of exercises. When the monkeys reached for items, electrodes measured the activity of neurons in their dorsal premotor cortex, a region of the brain that is involved in the perception of movement.

The monkeys were trained to reach for a virtual object on a screen to receive a reward. In some tasks the monkeys had to reach directly for an object, in others they had to reach around an obstacle to get to the target.

Impulsive grab

Moran and Pearce managed to identify the neural activity corresponding with several aspects of the planned movement, such as angle of reach, hand position and the final target location.

The findings could one day allow the design of prosthetic limbs that can be controlled with thought alone, which is “one of the reasons we did the study”, says Moran.

"The two subjects actually used different strategies to perform the task, and we were able to see this in their neural activity," Moran says. One monkey waited to receive all the information before reaching, but the other reached immediately, even though there was a good chance that an obstacle might appear and the reaching action would need to be rethought.

"If the decoding strategy is a robust finding, then this has wider consequences concerning mind-reading – particularly if we can get equivalent results for more complex strategic differences at higher cognitive levels," says Richard Cooper, a cognitive researcher at Birkbeck, University of London. "However, this is all very speculative."

Source: NewScientist