Posts tagged neuron

March 21, 2012

Amateurs have a new tool for conducting simple neuroscience experiments in their own garage: the SpikerBox.

As reported in the Mar. 21 issue of the open access journal PLoS ONE, the SpikerBox lets users amplify and listen to neurons’ electrical activity – like those in a cockroach leg or cricket torso – and is appropriate for use in middle or high school educational programs, or by amateurs.

The work was a project from Backyard Brains, a start-up company focused on developing neuroscience educational resources. In the paper, the authors, Timothy Marzullo and Gregory Gage, describe a sample experiment using a cockroach leg stuck with two needles and monitoring the electrical signals. They also provide instructions for using the SpikerBox to answer specific experimental questions, like how neurons carry information about touch, how the brain tells muscles to move, and how drugs affect neurons, and an online portal provides further instructional materials. These are just a few examples of the many ways this tool can be used.

"Our mission is to lower the barrier-to-entry for students interested in learning about the brain. We hope our manuscript finds its way into the hands of high school teachers around the world", says Dr. Marzullo.

Provided by Public Library of Science

Source: medicalxpress.com

March 21, 2012

Research at the University of Calgary’s Hotchkiss Brain Institute (HBI) has demonstrated the novel expression of an ion channel in Purkinje cells – specialized neurons in the cerebellum, the area of the brain responsible for movement. Ray W. Turner, PhD, Professor in the Department of Cell Biology & Anatomy and PhD student Jordan Engbers and colleagues published this finding in the January edition of the journal Proceedings of the National Academy of Sciences (PNAS).

This research identifies for the first time that an ion channel called KCa3.1 that was not previously believed to be expressed in the brain is actually present in Purkinje cells. In addition, these researchers demonstrate the mechanism by which this ion channel allows Purkinje cells to filter sensory input in order to coordinate the body’s movements.

The discovery was unexpected, as Engbers explains, “we didn’t specifically go looking for this channel. A lot of time was spent trying to identify the source for an electrical current that we were observing and we finally found ourselves asking ‘what evidence is there that KCa3.1 isn’t in the brain?’ So we ran some tests and all the pieces really fell into place.”

In the cerebellum, sensory input activates neurons called Purkinje cells that have to filter the information and respond only to relevant inputs to produce an appropriate movement response. Although this function of Purkinje cells has been well documented, Engbers and Turner take our understanding a step further by demonstrating that the KCa3.1 ion channel plays a key part in this process - acting as a gatekeeper to filter the enormous amount of incoming information.

As Turner explains, “these cells receive hundreds of thousands of signals every second from the body’s sensory systems. KCa3.1 then allows the cells to filter out the background noise and respond to only the three or four inputs that are particularly relevant”.

Engbers further describes the mechanism by which KCa3.1 filters out the unwanted information, “these channels are activated by an influx of calcium, which generates an inhibitory influence until the correct input is detected. Once the appropriate input is detected, the Purkinje cell responds with a burst of nerve impulses, which in turn initiates the proper motor response.”

This research fills a substantial gap in understanding how neurons in the cerebellum process information. Engbers and Turner expect that continued research will identify KCa3.1 in other areas of the brain and that it will be responsible for several still unexplained phenomena observed in neuronal recordings.

"What we have found will help us understand how the cerebellum functions normally. Now that we have shown the scientific community this new information, we expect that it will become clear that KCa3.1 plays a much wider role in brain function," says Engbers.

Provided by University of Calgary 

Source: medicalxpress.com

ScienceDaily (Mar. 8, 2012) — How do neurons in the brain communicate with each other? One common theory suggests that individual cells do not exchange signals among each other, but rather that exchange takes place between groups of cells. Researchers from Japan, the United States and Germany have now developed a mathematical model that can be used to test this assumption. Their results have been published in the current issue of the journal “PLoS Computational Biology.”

A neuron in the neocortex, the part of the brain that deals with higher brain functions, contacts thousands of other neurons and receives as many inputs from other neurons. Previously, it has been very difficult to use measured signals to interpret the way the cells work together. Scientists at the RIKEN Brain Science Institute (BSI) in Japan have now joined forces with researchers at the Forschungszentrum Jülich, Germany, and MIT in Boston, USA, to develop a mathematical model that can clarify the way neurons collaborate.

"From the many signals measured in parallel, the novel method filters the information on whether the neurons communicate individually or as a group," explains Dr. Hideaki Shimazaki from BSI. "Furthermore it takes into account that these groups of cells are not fixed but, instead, can organize themselves flexibly within milliseconds into groups of different composition, depending on the current requirements of the brain."

Prof. Sonja Grün from Forschungszentrum Jülich hopes that the method can help researchers to prove the existence of dynamic cell assemblies and clearly assign their activities to certain behaviors. The scientists already demonstrated that neurons work together when an animal anticipates a signal, which may allow it to have a more rapid or more sensitive response.

In future, the scientists hope to learn how to use their methods on the signals recorded from hundreds of neurons simultaneously. This would raise the probability of observing cell assemblies involved in planning and controlling behavior.

Source: Science Daily

March 7, 2012

Neurons (nerve cells) are labeled with green fluorescent protein, and other neurons in the brain are labeled in the background with either red or blue tracers. The small bulbs (i.e., dendritic spines) on the spidery dendrites show places where nerve cells connect and communicate, called synapses, and when these spines shrank over time, this predicted vocal degradation in the songbirds. Credit: Katie Tschida, Duke Department of Neurobiology

Portions of a songbird’s brain that control how it sings have been shown to decay within 24 hours of the animal losing its hearing.

The findings, by researchers at Duke University Medical Center, show that deafness penetrates much more rapidly and deeply into the brain than previously thought. As the size and strength of nerve cell connections visibly changed under a microscope, researchers could even predict which songbirds would have worse songs in coming days.

"When hearing was lost, we saw rapid changes in motor areas in that control song, the bird’s equivalent of speech," said senior author Richard Mooney, Ph.D., professor of neurobiology at Duke. "This study provided a laser-like focus on what happens in the living songbird brain, narrowed down to the particular cell type involved."

The study was published in Neuron journal online on March 7, 2012.

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Yale University researchers have discovered a key cellular mechanism that may help the brain control how much we eat, what we weigh, and how much energy we have.

The findings, published in the Feb. 28 issue of the Journal of Neuroscience, describe the regulation of a family of cells that project throughout the nervous system and originate in an area of the brain call the hypothalamus, which has been long known to control energy balances.

Scientists and pharmaceutical companies are closely investigating the role of melanin-concentrating hormone (MCH) neurons in controlling food intake and energy. Previous studies have shown that MCH makes lab animals eat more, sleep more, and have less energy. In contrast, other hypothalamic neurons use the thyrotropin-releasing hormone (TRH) as a neurotransmitter, and these neurons reduce food intake and body weight, and increase physical activity.

The Yale study of brains of mice shows that the two systems appear to act in direct opposition, to help the organism keep these crucial functions in balance.

Although TRH is normally an excitatory neurotransmitter, the Yale study shows that in mice TRH inhibits MCH cells by increasing inhibitory synaptic input. In contrast, TRH had little effect on other types of neurons also involved in energy regulation.

“That these two types of neurons interact at the synaptic level gives us clues as to how the brain controls the amount of food we eat, and how much we sleep,” said Anthony van den Pol, senior author and professor of neurosurgery at Yale School of Medicine.

Three MCH neurons in the hypothalamus region of a mouse brain are highlighted in green. In animals, these neurons are associated with high calorie intake and lower energy levels. Yale researchers have shown how the effects of these key cells are reversed. Image adapted from Yale press release image.

Source: Neuroscience News

Article Date: 27 Feb 2012 - 10:00 PST

In a study, due to appear in the March 30 issue of Cell, researchers at MIT’s Picower Institute for Learning and Memory have discovered, for the first time, that neurons at different stages of their life cycles potentially perform two separate functions, such as forming distinct memories of almost identical situations, and the ability to recall an entire event when prompted by a tiny detail.

The study describes a brain structure that produces new neurons in adults as a possible vital target for developing drugs for the treatment of memory disorders. 


Lead author, Toshiaki Nakashiba at the Picower Institute said that an imbalance between young and old neurons in the brain region, called dentate gyrus can potentially disrupt memory formation, recalling and potentially affect cognitive dysfunctions related to post-traumatic stress disorder (PTSD), as well as aging. In dentate gyrus, only one of the two brain sites continuously generates new neurons throughout adult life.

Co-author Susumu Tonegawa, Picower Professor of Neuroscience at the Picower Institute explained:

"In animals, traumatic experiences and aging often lead to decline of the birth of new neurons in the dentate gyrus. In humans, recent studies found dentate gyrus dysfunction and related memory impairments during normal aging."

The brain detects small differences between similar experiences by pattern separation. Humans are able to recall explicit content of earlier memories with only limited clues related to the original experience when these patterns are complete. For instance, a person who has dinner at the same French restaurant two nights in a row makes similar experiences or observations on both occasions, like the menu, the surroundings, the time of their visit, etc.

The distinct memories that the person’s brains forms for each event are called pattern separation. If a friend, for instance, mentions a liking for onion soup some time later, the person may recall not only the dish they had at the restaurant, but the entire experience of which people were at the restaurant, what they did after the meal, etc. This process is recalled by pattern completion. 


Whilst pattern separation forms a unique new memory based on differences between experiences, pattern completion recalls memories by identifying similarities. People who have suffered severe brain injury or trauma are often unable to recognize their family and friends’ faces that they see on a regular basis, whilst others with PTSD are unable to forget harrowing events.

Tonegawa explains:

"Impaired pattern separation due to loss of young neurons may shift the balance in favor of pattern completion, which may underlie recurrent traumatic memory recall observed in PTSD patients."

For a long time, neuroscientists believed that these two opposing and competing processes occur in different neural circuits within the hippocampus, thinking that the dentate gyrus, a structure of significant interest for its plasticity within the nervous system and its impact on conditions ranging from depression and epilepsy to traumatic brain injury, is involved in pattern separation, whilst the CA3 region is involved in pattern completion. However, the MIT researchers discovered that the neurons spawned by the dentate gyrus alone could potentially have distinct roles as they age.

The MIT researchers explored a pattern separation in mice that learned to distinguish between two chambers, of which one was safe and the other gave them an unpleasant shock to their feet. To assess the mice pattern completion abilities, the researchers gave the mice limited cues in finding their way out of a maze they knew how to negotiate earlier. They compared normal mice with mice that lacked young or old neurons, and discovered that the mice exhibited defects in pattern completion or separation, depending on which set of neurons was depleted. Previous research supported the idea that the dentate gyrus or young neurons performed pattern separation when examining pattern separation, by manipulating the entire dentate gyrus or only adult-born young neurons.

Nakashiba concluded:

"By studying mice genetically modified to block neuronal communication from old neurons—or by wiping out their adult-born young neurons—we found that old neurons were dispensable for pattern separation, whereas young neurons were required for it. Our data also demonstrated that mice devoid of old neurons were defective in pattern completion, suggesting that the balance between pattern separation and completion may be altered as a result of loss of old neurons."

Written by Petra Rattue  

Source: Medical News Today

Article Date: 24 Feb 2012 - 8:00 PST

A new study, in this week’s online edition of the Proceedings of the National Academy of Sciences , shows an incredible degree of biological diversity in a surprising location, i.e. in a single neural connection in the body wall of flies. The finding opens up a new spectrum of interesting questions regarding the importance of the nervous system structure and the evolution of neural wiring.

Geneticist Barry Ganetzky, Steenbock Professor of Biological Sciences at the University of Wisconsin-Madison declared:

 ”We know almost nothing about the evolution of the nervous system, although we know it has to happen - behaviors change, complexity changes, there is the addition of new neurons, formation of different synaptic connections.”

The finding proves even more astounding given that Ganetzky and his graduate student Megan Campbell discovered the unexpected diversity in a location very familiar to scientists, i.e. the neuromuscular junction 4 (NMJ4), the location where a single motor neuron contacts a particular muscle in the fly body wall to drive its activity. The synapses where neurons link to their neuronal or muscular targets have a complex structural form, looking like miniature trees decorated with tiny bulbs that are the nerve terminals (synaptic boutons).

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February 22nd, 2012

The notion of a pain switch is an alluring idea, but is it realistic? Well, chemists at LMU Munich, in collaboration with colleagues in Berkeley and Bordeaux, have now shown in laboratory experiments that it is possible to inhibit the activity of pain-sensitive neurons using an agent that acts as a photosensitive switch. For the LMU researchers, the method primarily represents a valuable tool for probing the neurobiology of pain. (Nature Methods, 19.02.2012)

The system developed by the LMU team, led by Dirk Trauner, who is Professor of Chemical Biology and Genetics, is a chemical compound they call QAQ. The molecule is made up of two functional parts, each containing a quaternary ammonium, which are connected by a nitrogen double bond (N=N). This bridge forms the switch, as its conformation can be altered by light. Irradiation with light of a specific wavelength causes the molecule to flip from a bent to an extended form; exposure to light of a different color reverses the effect.

One half of QAQ closely resembles one of the active analogs of lidocaine, a well-known local anesthetic used by dentists. Lidocaine blocks the perception of pain by inhibiting the action of receptors found on specific nerve cells in the skin, which respond to painful stimuli and transmit signals to the spinal cord.

Neuroreceptors are proteins that span the outer membrane of nerve cells. They possess deformable pores that open in response to appropriate stimuli, and function as conduits that permit electrically charged ions to pass into or out of the cells. The ion channel targeted by the lidocaine-like end of QAQ responds to heat by allowing positively charged sodium ions to pass into the cells that express it. This alters the electrical potential across the membrane, which ultimately leads to transmission of the nerve impulse.

In their experiments, the researchers exploited the fact that QAQ can percolate through endogenous ion channels to get the molecule into nerve cells. This is a crucial step, because its site of action is located on the inner face of the targeted ion channel.

Furthermore, the lidocaine-like end of QAQ binds to this site only if the molecule is in an extended conformation. When the cells were irradiated with 380-nm light, which bends the bridge, signal transmission was reactivated within a matter of milliseconds. Exposure to light with a wavelength of 500 nm, on the other hand, reverts the molecule to the extended form and restores its inhibitory action. The analgesic effect of the switch was confirmed using an animal model.
Trauner’s team has been working for some considerable time on techniques with which biologically critical molecular machines such as neuroreceptors can be controlled in living animals by means of light impulses. The researchers themselves regard the new method primarily as a tool for neurobiological studies, particularly for pain research. Therapeutic applications of the principle are “a long way off”, says Timm Fehrentz, one of Dirk Trauner’s PhD students and one of the two equal first authors on the new paper. For one thing, the monochromatic light used to isomerize the QAQ molecule cannot penetrate human skin sufficiently to reach the pain-sensitive neurons. The researchers hope to address that problem by looking for alternatives to QAQ that respond to red light of longer wavelength, which more readily passes through the skin. (math/PH)

Source: Neuroscience News

ScienceDaily (Feb. 21, 2012) — The carnage evident in disasters like car wrecks or wartime battles is oftentimes mirrored within the bodies of the people involved. A severe wound can leave blood vessels and nerves severed, bones broken, and cellular wreckage strewn throughout the body — a debris field within the body itself.

Thriving DRG cells. (Credit: Image courtesy of University of Rochester Medical Center)

It’s scenes like this that neurosurgeon Jason Huang, M.D., confronts every day. Severe damage to nerves is one of the most challenging wounds to treat for Huang and colleagues. It’s a type of wound suffered by people who are the victims of gunshots or stabbings, by those who have been involved in car accidents — or by soldiers injured on the battlefield, like those whom Huang treated in Iraq.

Now, back in his university laboratory, Huang and his team have taken a step forward toward the goal of repairing nerves in such patients more effectively. In a paper published in the journal PLoS ONE, Huang and colleagues at the University of Rochester Medical Center report that a surprising set of cells may hold potential for nerve transplants.

In a study in rats, Huang’s group found that dorsal root ganglion neurons, or DRG cells, help create thick, healthy nerves, without provoking unwanted attention from the immune system.

The finding is one step toward better treatment for the more than 350,000 patients each year in the United States who have serious injuries to their peripheral nerves. Huang’s laboratory is one of a handful developing new technologies to treat such wounds.

"These are very serious injuries, and patients really suffer, many for a very long time," said Huang, associate professor of Neurosurgery and chief of Neurosurgery at Highland Hospital, an affiliate of the University of Rochester Medical Center. "There are a variety of options, but none of them is ideal.

"Our long-term goal is to grow living nerves in the laboratory, then transplant them into patients and cut down the amount of time it takes for those nerves to work," added Huang, whose project was funded by the National Institute of Neurological Disorders and Stroke and by the University of Rochester Medical Center.

For a damaged nerve to repair itself, the two disconnected but healthy portions of the nerve must somehow find each other through a maze of tissue and connect together. This happens naturally for a very small wound — much like our skin grows back over a small cut — but for some nerve injuries, the gap is simply too large, and the nerve won’t grow back without intervention.

For surgeons like Huang, the preferred option is to transplant nerve tissue from elsewhere in the patient’s own body — for instance, a section of a nerve in the leg — into the wounded area. The transplanted nerve serves as scaffolding, a guide of sorts for a new nerve to grow and bridge the gap. Since the tissue comes from the patient, the body accepts the new nerve and doesn’t attack it.

But for many patients, this treatment isn’t an option. They might have severe wounds to other parts of the body, so that extra nerve tissue isn’t available. Alternatives can include a nerve transplant from a cadaver or an animal, but those bring other challenges, such as the lifelong need for powerful immunosuppressant drugs, and are rarely used.

One technology used by Huang and other neurosurgeons is the NeuraGen Nerve Guide, a hollow, absorbable collagen tube through which nerve fibers can grow and find each other. The technology is often used to repair nerve damage over short distances less than half an inch long.

In the PLoS One study, Huang’s team compared several methods to try to bridge a nerve gap of about half an inch in rats. The team transplanted nerve cells from a different type of rat into the wound site and compared results when the NeuraGen technology was was used alone or when it was paired with DRG cells or with other cells known as Schwann cells.

After four months, the team found that the tubes equipped with either DRG or Schwann cells helped bring about healthier nerves. In addition, the DRG cells provoked less unwanted attention from the immune system than the Schwann cells, which attracted twice as many macrophages and more of the immune compound interferon gamma.

While both Schwann and DRG cells are known players in nerve regeneration, Schwann cells have been considered more often as potential partners in the nerve transplantation process, even though they pose considerable challenges because of the immune system’s response to them.

"The conventional wisdom has been that Schwann cells play a critical role in the regenerative process," said Huang, who is a scientist in the Center for Neural Development and Disease. "While we know this is true, we have shown that DRG cells can play an important role also. We think DRG cells could be a rich resource for nerve regeneration."

In a related line of research, Huang along with colleagues in the laboratory of Douglas H. Smith, M.D. , at the University of Pennsylvania are creating DRG cells in the laboratory by stretching them, which coaxes them to grow about one inch every three weeks. The idea is to grow nerves several inches long in the laboratory, then transplant them into the patient, instead of waiting months after surgery for the nerve endings to travel that distance within the patient to ultimately hook up.

Source: Science Daily

February 16, 2012

(Medical Xpress) — Gene therapy not only helps injured brain cells to live longer and regenerate, but also changes the shape of the cells, according to researchers The University of Western Australia. 

The study, published in the international science and medicine journal PLoS One, was led by Winthrop Professor Alan Harvey from UWA’s School of Anatomy, Physiology and Human Biology, and Associate Professor Jennifer Rodger, NHMRC Research Fellow in Experimental and Regenerative Neurosciences at UWA’s School of Animal Biology.  The research was funded primarily by the WA Neurotrauma Research Program.

Professor Harvey said gene therapy was a relatively new strategy that attempted to help injured brain cells survive and regrow.

"Our previous work has shown that when growth-promoting genes are introduced into injured brain cells for long periods of time (up to nine months), the cells’ capacity for survival and regeneration is significantly increased," he said.

"We have now shown that these same neurons have also changed shape in response to persistent over-expression of the growth factors.  Importantly, it is not just neurons containing the introduced growth-promoting gene that are affected, but neighbouring "bystander" neurons."

Professor Harvey said neural morphology was very important in determining how a cell communicated with other cells and formed the circuits that allowed the brain to function.

"Any changes in morphology are therefore likely to alter the way neurons receive and transmit information.  These changes may be beneficial but could also interfere with normal brain circuits, reducing the benefits of improved survival and regeneration."

Professor Harvey said the results were significant for those involved in designing gene therapy-based protocols to treat brain and spinal cord injury and degeneration.

"These new results suggest that we may need to be careful about the types of genes we use in neurotherapy and how long we continue the therapy.  While it may be beneficial for these genes to move around and cause changes in other cells, we need to be able to switch them off once the change has taken place."

Provided by University of Western Australia

Source: medicalxpress.com