Posts tagged neuron

May 21, 2012

Max Planck scientists discover brain cells in monkeys that may be linked to self-awareness and empathy in humans.

The anterior insular cortex is a small brain region that plays a crucial role in human self-awareness and in related neuropsychiatric disorders. A unique cell type – the von Economo neuron (VEN) – is located there. For a long time, the VEN was assumed to be unique to humans, great apes, whales and elephants. Henry Evrard, neuroanatomist at the Max Planck Institute for Biological Cybernetics in Tübingen, Germany, now discovered that the VEN occurs also in the insula of macaque monkeys. The morphology, size and distribution of the monkey VEN suggest that it is at least a primal anatomical homolog of the human VEN. This finding offers new and much-needed opportunities to examine in detail the connections and functions of a cell and brain region that could have a key role in human self-awareness and in mental disorders including autism and specific forms of dementia.

The insular cortex, or simply insula, is a hidden cortical region folded and tucked away deep in the brain – an island within the cortex. Within the last decade, the insula has emerged from darkness as having a key role in diverse functions usually linked to our internal bodily states, to our emotions, to our self-awareness, and to our social interactions. The very anterior part of the insula in particular is where humans consciously sense subjective emotions, such as love, hate, resentment, self-confidence or embarrassment. In relation to these feelings, the anterior insula is involved in various psychopathologies. Damage of the insula leads to apathy, and to the inability to tell what feelings we or our conversational partner experience. These inabilities and alteration of the insula are also encountered in autism and other highly detrimental neuropsychiatric disorders including the behavioural variant of frontotemporal dementia (bvFTD).

The von Economo neuron (VEN) occurs almost exclusively in the anterior insula and anterior cingulate cortex. Until recently it was believed that the VEN is only present in humans, great apes and some large-brained mammals with complex social behaviour such as whales and elephants. In contrast to the typical neighbouring pyramidal neuron that is present in all mammals and all brain regions, the VEN has a peculiar spindle shape and is about three times as large. Their numeral density is selectively altered in autism and bvFTD. Henry Evrard and his team, at the Max Planck Institute for Biological Cybernetics in Tübingen now discovered VENs in the anterior insula in macaque monkeys. His present work provides compelling evidence that monkeys possess at least a primitive form of the human VEN although they do not have the ability to recognize themselves in a mirror, a behavioural hallmark of self-awareness.

"This means, other than previously believed, that highly concentrated VEN populations are not an exclusivity of hominids, but also occurs in other primate species", explains Henry Evrard. "The VEN phylogeny needs to be reexamined. Most importantly, the very much-needed analysis of the connections and physiology of these specific neurons is now possible.” Knowing the functions of the VEN and its connections to other regions of the brain in monkeys could give us clues on the evolution of the anatomical substrate of self-awareness in humans and may help us in better understanding serious neuropsychiatric disabilities including autism, or even addictions such as to drugs or smoking.

Provided by Max Planck Society

Source: medicalxpress.com

May 11, 2012

Neurons are arranged in periodic patterns that repeat over large distances in two areas of the cerebral cortex, suggesting that the entire cerebral cortex has a stereotyped organization, reports a team of researchers led by Toshihiko Hosoya of the RIKEN Brain Science Institute. The entire cortex has a stereotypical layered structure with the same cell types arranged in the same way, but how neurons are organized in the other orientation—parallel to the brain’s surface—is poorly understood.

Figure 1: In the mouse visual cortex, neurons expressing id2 mRNA (magenta) are found in regularly repeating clusters. Reproduced from Ref. 1 © 2011 Hisato Maruoka et al., RIKEN Brain Science Institute

Hosoya and his colleagues therefore examined layer V (5) of the mouse cortex, which contains two classes of large pyramidal neurons that look identical but differ in the connections they form. One projects axons straight down to regions beneath the cortex; the other projects to the cortex on the opposite side of the brain.

First, the researchers examined expression of the id2 gene in cells of the visual cortex, because these cells form clusters in that part of the brain. They found that id2 is expressed in nearly all cells that project axons downward, but not in those that cross over. Hosoya and colleagues verified this by visualizing the connections of cells using fluorescent cholera toxin, which binds to cell membranes and travels along the axons.

Further examination of gene expression patterns in tissue slices revealed that the cells are arranged in clusters aligned perpendicular to the brain’s surface, and that the clusters are organized in a regular pattern, with the same basic unit repeating every thirty micrometers (Fig. 1). They also observed the same pattern in layer V of the somatosensory cortex, suggesting that this organization is common to all other areas.

By generating a strain of mutant mice expressing green fluorescent protein in the progenitor cells that produce the cells in layer V during brain development, Hosoya and his colleagues investigated the embryonic origin of these cells. This revealed that each cluster contains neurons that are produced by different progenitor cells.

Finally, the researchers showed that the regular pattern persists in the adult visual cortex, and that neurons in each cluster show the same activity patterns in response to visual stimulation. “Our preliminary data suggest that at least several other areas in the cortex have the same structure,” says Hosoya. “It’s likely that the entire cortex has the same organization, and I expect that the human cortex has the same structure.”

Provided by RIKEN

Source: medicalxpress.com

May 10th, 2012

Glial cells pass on metabolites to neurons.

Around 100 billion neurons in the human brain enable us to think, feel and act. They transmit electrical impulses to remote parts of the brain and body via long nerve fibres known as axons. This communication requires enormous amounts of energy, which the neurons are thought to generate from sugar. Axons are closely associated with glial cells which, on the one hand, surround them with an electrically insulating myelin sheath and, on the other hand support their long-term function. Klaus Armin and his research group from the Max Planck Institute of Experimental Medicine in Göttingen have now discovered a possible mechanisms by which these glial cells in the brain can support their associated axons and keep them alive in the long term.

Oligodendrocytes are a group of highly specialised glial cells in the central nervous system. They are responsible for the formation of the fat-rich myelin sheath that surrounds the nerve fibres as an insulating layer. The comparison with the coating on electricity cables is an obvious one; however, myelin can do much more than act as the insulating layer on electricity cables: it increases the transmission speed of the axons and also reduces ongoing energy consumption. The extreme importance of myelin for a functioning nervous system is shown by the diseases that arise from a defective insulating layer, such as multiple sclerosis

Interestingly, the function of the oligodendrocytes goes far beyond the mere provision of myelin. Klaus-Armin Nave and his team at the Max Planck Institute in Göttingen already succeeded in demonstrating years ago that healthy glial cells are also essential for the long-term function and survival of the axons themselves, irrespective of myelination. “The way in which the oligodendrocytes functionally support their associated axons was not clear to us up to now,” says Nave. In a new study, the researchers were able to show that the glial cells are involved in, among other things, the replenishment of energy in the nerve fibres. “They could be described as the petrol stations on the data highway of the axons,” says Nave, explaining the results.

Electron microscope cross-section image of the nerve fibres (axons) of the optic nerve. Axons are surrounded by special glial cells, the oligodendrocytes, wrapping themselves around the axons in several layers. Between the axons, there are extensions of astrocytes, another type of glial cells. © K.-A.Nave/MPI f. Experimental Medicine

But how does the energy refuelling work? Is there a metabolic connection between the oligodendrocytes and axons? To find out, Ursula Fünfschilling generated genetically modified mice: the function of the mitochondria was deliberately disrupted in the oligodendrocytes through the inactivation of the Cox10 gene. This affects the final stages of sugar breakdown taking place in the mitochondria where energy is harnessed – a process known as the respiratory chain. If a link in this chain is missing, in this instance cytochrome oxidase, which is only functional when cells have the enzyme Cox10, the glial cells gradually lose the capacity for cell respiration in their mitochondria. “Without independent breathing, the manipulated glial cells of the nervous systems should have died,” explains the scientist. That is, unless the low level of energy harnessed from the splitting of the glucose to form pyruvate or milk acid, a process known as glycolysis, is sufficient for them.

And this is precisely what the scientists observed in their mice: the animals’ myelin was initially formed in the normal way. The loss of the mitochondrial respiratory chain, which started at this point, did not appear to affect the glial cells in the central nervous system. Even one year later, there were no neurodegenerative changes in the brain to be observed. The scientists assume that in the early weeks of life – a phase characterised by maximum energy requirement – the mutated oligodendrocytes still rely on many intact mitochondria. All of the more mature oligodendrocytes later appear to reduce the mitochondrial respiration and set it to energy generation through increased glycolysis. This has the advantage in healthy glial cells that the metabolic products which arise during the breaking down of glucose can be used as components for myelin synthesis. In addition, the lactic acid that arises in the oligodendrocytes can be given to the axons where it can be used to produce energy with the help of the axon’s own mitochondria.

“The complete loss of the respiratory chain in the deliberately modified oligodendrocytes probably elevates a developmental step that unfolds naturally,” explains Nave. Thus the loss of glial mitochondria does not result in the deterioration of the energy supply to the axons but, conversely, to an oversupply of exploitable lactic acid. The affected nerve pathways themselves have no problem demonstrably in metabolising the lactic acid from oligodendrocytes. Transport proteins ensure the rapid transfer of the lactic acid between the oligodendrocytes and their myelinated axons.

This finding provides a new understanding of the role of oligodendrocytes: in addition to their known significance for myelinisation [aka myelination], they can directly provide the axons with glucose products that can be used as fuel with the help of axonal mitochondria in periods of high activity. This coupling of glial cells could explain, among other things, why in many myelin diseases, for example multiple sclerosis, the affected demyelinised axons often suffer irreversible damage.

Source: Neuroscience News

May 6, 2012

Gaining access to the inner workings of a neuron in the living brain offers a wealth of useful information: its patterns of electrical activity, its shape, even a profile of which genes are turned on at a given moment. However, achieving this entry is such a painstaking task that it is considered an art form; it is so difficult to learn that only a small number of labs in the world practice it.

Researchers at MIT and the Georgia Institute of Technology have developed a way to automate a process called whole-cell patch clamping, which involves bringing a tiny hollow glass pipette in contact with the cell membrane of a neuron, then opening up a small pore in the membrane to record the electrical activity within the cell. Credit: Sputnik Animation and MIT McGovern Institute

But that could soon change: Researchers at MIT and the Georgia Institute of Technology have developed a way to automate the process of finding and recording information from neurons in the living brain. The researchers have shown that a robotic arm guided by a cell-detecting computer algorithm can identify and record from neurons in the living mouse brain with better accuracy and speed than a human experimenter.

The new automated process eliminates the need for months of training and provides long-sought information about living cells’ activities. Using this technique, scientists could classify the thousands of different types of cells in the brain, map how they connect to each other, and figure out how diseased cells differ from normal cells.

The project is a collaboration between the labs of Ed Boyden, associate professor of biological engineering and brain and cognitive sciences at MIT, and Craig Forest, an assistant professor in the George W. Woodruff School of Mechanical Engineering at Georgia Tech.

"Our team has been interdisciplinary from the beginning, and this has enabled us to bring the principles of precision machine design to bear upon the study of the living brain," Forest says. His graduate student, Suhasa Kodandaramaiah, spent the past two years as a visiting student at MIT, and is the lead author of the study, which appears in the May 6 issue of Nature Methods.

The method could be particularly useful in studying brain disorders such as schizophrenia, Parkinson’s disease, autism and epilepsy, Boyden says. “In all these cases, a molecular description of a cell that is integrated with [its] electrical and circuit properties … has remained elusive,” says Boyden, who is a member of MIT’s Media Lab and McGovern Institute for Brain Research. “If we could really describe how diseases change molecules in specific cells within the living brain, it might enable better drug targets to be found.”

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May 5, 2012 

In an effort to identify the underlying causes of neurological disorders that impair motor functions such as walking and breathing, UCLA researchers have developed a novel system to measure the communication between stem cell-derived motor neurons and muscle cells in a Petri dish.

The study provides an important proof of principle that functional motor circuits can be created outside of the body using stem cell-derived neurons and muscle cells, and that the level of communication, or synaptic activity, between the cells could be accurately measured by stimulating motor neurons with an electrode and then measuring the transfer of electrical activity into the muscle cells to which the motor neurons are connected.

When motor neurons are stimulated, they release neurotransmitters that depolarize the membranes of muscle cells, allowing the entry of calcium and other ions that cause them to contract. By measuring the strength of this activity, one can get a good estimation of the overall health of motor neurons. That estimation could shed light on a variety of neurodegenerative diseasessuch as spinal muscular atrophy and amyotrophic lateral sclerosis, or Lou Gehrig’s disease, in which the communication between motor neurons and muscle cells is thought to unravel, said study senior author Bennett G. Novitch, an assistant professor of neurobiology and a scientist with the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.

The findings of the study appear May 4, 2012 in PLoS ONE, a peer-reviewed journal of the Public Library of Science.

"Now that we have this method to measure the strength of the communications between motor neurons and muscle cells, we may be able to begin exploring what happens in the earliest stages of motor neuron disease, before neuronal death becomes prevalent," Novitch said. "This can help us to pinpoint where things begin to go wrong and provide us with new clues into therapeutic interventions that could improve synaptic communication and promote neuronal survival."

Novitch said the synaptic communication activity his team was able to create and measure using mouse embryonic stem cell-derived motor neurons and muscle cells looks very similar what is seen in a mouse, validating that their model is a realistic representation of what is happening in a living organism.

"That gives us a good starting point to try to model what happens in cells that harbor genetic mutations that are associated with neurodegenerative diseases,. To do that, we had to first define an activity profile of normal synaptic communication," he said. "Some research suggests that a breakdown in this communication can be an early indication of disease progression or possibly an initiating event. Neurons that cannot effectively transmit information to muscle cells will eventually withdraw their contacts, causing both the neurons and muscle cells to degenerate over time. Hopefully, we can now create disease models that will allow us to study what is happening."

In this study, Novitch and his team, led by Joy Umbach, an associate professor of molecular and medical pharmacology, used mouse embryonic stem cells to create the motor neurons and previously established lines of muscle precursors to produce muscle fibers. They put both cells together in a Petri dish, and the cells were cultured in such a way to encourage communication. Novitch said the team wanted to see if they would naturally form synaptic contacts and whether or not there was neural transmission between them.

In less than a week, the neurons had reached out to the muscle cells and assembled the protein networks needed for synaptic communication, Novitch said.

To measure the connections between the cells, the scientists used a technique called dual patch clamp recording. Pipettes containing stimulating and recording electrodes are inserted into the membranes of the motor neurons and muscle cells, being careful not to injure them. With this method, they were able send an electrical current into the motor neurons and measure responses in the muscle cells, as well as visualize the muscular contractions.

"The in vitro system developed here might accordingly be expanded to assess the underlying cellular and molecular mechanisms that contribute to this decline in synaptic input to motor neurons," the study states. "Thus, in addition to their utility for helping to answer fundamental biological questions, these co-cultures have clear applications in addressing problems of medical significance."

Going forward, Novitch and his team hope to recreate and confirm the work using human stem cell-derived motor neurons and muscle cells and measure the synaptic communications with newly developed optical recording methods, which are less invasive than the patch clamp techniques used in this study.

Provided by University of California, Los Angeles

Source: medicalxpress.com

May 2, 2012 

The brain’s neurons are coupled together into vast and complex networks called circuits. Yet despite their complexity, these circuits are capable of displaying striking examples of collective behavior such as the phenomenon known as “neuronal avalanches,” brief bursts of activity in a group of interconnected neurons that set off a cascade of increasing excitation.

In a paper published in the American Institute of Physics’ journal Chaos, an international team of researchers from China, Hong Kong, and Australia explores connections between neuronal avalanches and a model of learning – a rule for how neurons “choose” to connect among themselves in response to stimuli. The learning model, called spike time-dependent plasticity, is based on observations of real behavior in the brain.

The researchers’ simulations reveal that the complex neuronal circuit obtained from the learning model would also be good at generating neuronal avalanches. This agreement between the model and a real, proven behavior of neurons suggests that the learning model is an accurate way to describe how the brain processes information.

The authors say their work could aid an understanding of how learning could lead to the formation of cortical structures in the brain, as well as why the resulting structures are so efficient at processing large amounts of information. “While [the finding] is entirely consistent with existing neurophysiology, our work is the first to provide this concrete link” between this particular learning rule and neuronal avalanches, says co-author Michael Small of the University of Western Australia. “It provides a simple, and therefore perhaps surprising, explanation for how a system as complex as the cortex can generate such striking collective behavior.”

Provided by American Institute of Physics

Source: medicalxpress.com

May 2, 2012

Collaborative research by groups headed by scientists Joan J. Guinovart and Marco Milán at the Institute for Research in Biomedicine (IRB Barcelona) has revealed conclusive evidence about the harmful effects of the accumulation of glucose chains (glycogen) in fly and mouse neurons.

This image shows a cerebellum sample from a healthy mouse. Credit: Jordi Duran (IRB Barcelona)

These two animal models will allow scientists to address the genes involved in this harmful process and to find pharmacological solutions that allow disintegration of the accumulations or limitation of glycogen production. Advances in this direction would make a significant contribution to investigation into Lafora progressive myoclonic epilepsy and other neurodegenerative diseases characterized by glycogen accumulation in neurons. The journal EMBO Molecular Medicine publishes the results of the study this week.

This image shows the same tissue (mouse cerebellum) after glycogen accumulation. Credit: Jordi Duran (IRB Barcelona)

"Our data clearly indicate that glycogen accumulation alone kills neurons and thus dramatically reduces lifespan", explains Guinovart, an expert in glycogen metabolism, group leader at IRB Barcelona, and senior professor at the University of Barcelona, "because the only thing we have manipulated in the neurons is their capacity to produce glycogen".

The inclusion of the Drosophila fly in the study provides in vivo confirmation of the theory in another animal model as these flies also show the same symptoms of degeneration as mice when glycogen accumulates in neurons. However, in addition the use of Drosophila will speed up obtaining genetic data and the screening of therapeutic molecules. “In a short time we will be able to perform a massive search for genes involved in the pathological process and to understand it better at the molecular level”, emphasizes Marco Milán, ICREA researcher at IRB Barcelona and a specialist inDrosophila. “But the flies will also be useful to identify pharmacological molecules that can cure”, he explains.

The IRB Barcelona teams are designing several experiments to identify the possible therapeutic targets that may be useful to prevent glycogen accumulation in neurons. In addition to the direct relation to Lafora epilepsy, a progressive degenerative disease that affects adolescents and has no cure, glycogen accumulation could be the main cause of other neurodegenerative illnesses such as Adult polyglucosan body disease and Andersen’s disease.

Provided by Institute for Research in Biomedicine (IRB Barcelona)

Source: medicalxpress.com

April 26, 2012

What happens at the level of individual neurons while we learn? This question intrigued the neuroscientist Daniel Huber, who recently arrived at the Department of Basic Neuroscience at the University of Geneva. During his stay in the United States, he and his team tried to unravel the network mechanisms underlying learning and memory at the level of the cerebral cortex.

What’s the role of individual neurons in behavior? Do they always participate in the same functions? How do their responses evolve during learning?” asks the professor. One way to address these questions is to follow the activity of a large set of neurons while the subject learns a novel task. The goal is to link the behavioral changes with the changes in neuronal representations.

It’s currently impossible to follow the activity of a large number of individual neurons in humans, but the team of researchers quickly realized that mice are excellent subjects for such studies. “We were surprised by capacities of these small rodents. They learn novel associations quickly and are able to focus for hours on complex behavioral tasks. However, it is important to keep them motivated by rewarding them accordingly. They are very similar to us in that way.”

The behavioral task of the mice consisted in sampling the area in front of their snout with their whiskers to search for a small object. The object was presented either within reach and out of reach of their whiskers. Each time the object was detected with the whiskers, the mouse had to respond by licking to a reward spout. The correct choices were rewarded with a drop of liquid. “In this task different sensory and motor circuits have to interact in order to establish a novel association, leading to better and better performance”.

Remained the problem of how to follow the activity of the large number of neurons across many days of learning. The researchers replaced a small part of the bone overlying motor cortex with a tiny glass window. The neurons underneath the window were genetically modified to express a fluorescent marker which changes its intensity according to the activity of the neurons. This window into the brain allowed the researches around Daniel Huber to use two-photon microscopy to record the activity of the same set of 500 neurons during days of learning. 

"We then correlated the activity of the individual neurons with the different actions of the mouse, such as moving the whiskers, touching the object or licking at the right moment. It’s like synchronizing the soundtrack with the images in a movie" adds the neuroscientist. The researchers analyzed this data using a series of computational approaches to establish a link between the neuronal activity and the different sensory and motor features of the task. This allowed them to build algorithmic models that can predict different motor outputs by solely monitoring the neuronal activity. Decoding the neuronal activity allowed the researchers then to construct functional maps of the recorded neurons and quantify each neuron’s link with the different aspects of the behavior.

These functional maps revealed several fundamental findings: “Although the movements of the whiskers became more and more precise and targeted to search for the object during the learning, their relative neuronal representation remained relatively stable. In contrast, the representation of licking to respond and collect the rewards became more and more pronounced”. Taken together, only selected aspects of the learned behavior induced changes it the neuronal representation in the cortex. The scientists also found that different sensory and motor representations are spatially intermingled in the rodent brain.

Other analysis revealed that individual neurons remain stably linked to a given behavioral function, but they have a flexibility to remain silent on a given day. This functional stability despite a flexibility to join (or not) a given representation was actually suggested by different theoretical work on learning.

"If these characteristics are limited to the motor cortex or if these are more general rules that are apply across the cerebral cortex remains open" says Daniel Huber. That in fact this is one of the questions we are currently investigating in my lab in Geneva".

Provided by University of Geneva

Source: medicalxpress.com

March 26, 2012 by Bob Yirka

(Medical Xpress) — A research team made up of people from a wide variety of biological sciences has found that mice fed a diet high in fat tend to see an increase in the number of neurons created in the hypothalamus, a region of the brain associated with regulating energy use in the body. The team, as they describe in their paper published in Nature Neuroscience, write that the increase in neurons occurs in a part of the hypothalamus called the median eminence, which lies outside the blood-brain barrier.

Hypothalamic proliferative zone. For more details, Nature Neuroscience (2012) doi:10.1038/nn.3079

Suspecting that something unusual goes on with the hypothalamus and the median eminence in particular, when mice eat more fat, the research team put a group of mice on a diet very high in it. In the lab, mice are usually fed a diet that is approximately thirty five percent fat, which keeps them from gaining weight. In this study, the fat content was raised to sixty percent, which of course caused the mice to get fat. But, the team found, it also caused the creation of new brain cells in the median eminence to increase, from one to five percent.

Next the researchers forced the mouse brains to stop creating new brain cells while continuing to feed the mice the high fat diet. And surprisingly, the mice weight gain slowed and the mice demonstrated more energy. Adding to the good news was the fact that the median eminence lies outside of the blood-brain area (a separation of blood and brain fluid that prevents many materials in blood from reaching brain cells) meaning that the possibility of developing a therapy based on this research to help humans lose weight might be possible.

The researchers are quick to point out however, that there is no evidence yet that increased neuron production occurs in people who eat extra amounts of fat, or even in any other animal. They also say they don’t yet understand why new neuron growth occurs when mice are fed a high fat diet, but speculate that it may have something to do with detecting chemicals in the bloodstream and responding by sending signals to the rest of the hypothalamus.

More information: Tanycytes of the hypothalamic median eminence form a diet-responsive neurogenic niche, Nature Neuroscience (2012) doi:10.1038/nn.3079

Source: medicalxpress.com