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

ScienceDaily (Mar. 8, 2012) — UT Southwestern Medical Center investigators have identified a genetic manipulation that increases the development of neurons in the brain during aging and enhances the effect of antidepressant drugs.

UT Southwestern Medical Center investigators have identified a genetic manipulation that increases the development of neurons in the brain during aging and enhances the effect of antidepressant drugs. (Credit: © rolffimages / Fotolia)

The research finds that deleting the Nf1 gene in mice results in long-lasting improvements in neurogenesis, which in turn makes those in the test group more sensitive to the effects of antidepressants.

"The significant implication of this work is that enhancing neurogenesis sensitizes mice to antidepressants — meaning they needed lower doses of the drugs to affect ‘mood’ — and also appears to have anti-depressive and anti-anxiety effects of its own that continue over time," said Dr. Luis Parada, director of the Kent Waldrep Center for Basic Research on Nerve Growth and Regeneration and senior author of the study published in The Journal of Neuroscience.

Just as in people, mice produce new neurons throughout adulthood, although the rate declines with age and stress, said Dr. Parada, chairman of developmental biology at UT Southwestern. Studies have shown that learning, exercise, electroconvulsive therapy and some antidepressants can increase neurogenesis. The steps in the process are well known but the cellular mechanisms behind those steps are not.

"In neurogenesis, stem cells in the brain’s hippocampus give rise to neuronal precursor cells that eventually become young neurons, which continue on to become full-fledged neurons that integrate into the brain’s synapses," said Dr. Parada, an elected member of the National Academy of Sciences, its Institute of Medicine, and the American Academy of Arts and Sciences.

The researchers used a sophisticated process to delete the gene that codes for the Nf1 protein only in the brains of mice, while production in other tissues continued normally. After showing that mice lacking Nf1 protein in the brain had greater neurogenesis than controls, the researchers administered behavioral tests designed to mimic situations that would spark a subdued mood or anxiety, such as observing grooming behavior in response to a small splash of sugar water.

The researchers found that the test group mice formed more neurons over time compared to controls, and that young mice lacking the Nf1 protein required much lower amounts of anti-depressants to counteract the effects of stress. Behavioral differences between the groups persisted at three months, six months and nine months. “Older mice lacking the protein responded as if they had been taking antidepressants all their lives,” said Dr. Parada.

"In summary, this work suggests that activating neural precursor cells could directly improve depression- and anxiety-like behaviors, and it provides a proof-of-principle regarding the feasibility of regulating behavior via direct manipulation of adult neurogenesis," Dr. Parada said.

Dr. Parada’s laboratory has published a series of studies that link the Nf1 gene — best known for mutations that cause tumors to grow around nerves — to wide-ranging effects in several major tissues. For instance, in one study researchers identified ways that the body’s immune system promotes the growth of tumors, and in another study, they described how loss of the Nf1 protein in the circulatory system leads to hypertension and congenital heart disease.

Source: Science Daily

March 9, 2012

(Medical Xpress) — Despite a century of research, memory encoding in the brain has remained mysterious. Neuronal synaptic connection strengths are involved, but synaptic components are short-lived while memories last lifetimes. This suggests synaptic information is encoded and hard-wired at a deeper, finer-grained molecular scale.

In an article in the March 8 issue of the journal PLoS Computational Biology, physicists Travis Craddock and Jack Tuszynski of the University of Alberta, and anesthesiologist Stuart Hameroff of the University of Arizona demonstrate a plausible mechanism for encoding synaptic memory in microtubules, major components of the structural cytoskeleton within neurons.

Microtubules are cylindrical hexagonal lattice polymers of the protein tubulin, comprising 15 percent of total brain protein. Microtubules define neuronal architecture, regulate synapses, and are suggested to process information via interactive bit-like states of tubulin. But any semblance of a common code connecting microtubules to synaptic activity has been missing. Until now.

The standard experimental model for neuronal memory is long term potentiation (LTP) in which brief pre-synaptic excitation results in prolonged post-synaptic sensitivity. An essential player in LTP is the hexagonal enzyme calcium/calmodulin-dependent protein kinase II (CaMKII). Upon pre-synaptic excitation, calcium ions entering post-synaptic neurons cause the snowflake-shaped CaMKII to transform, extending sets of 6 leg-like kinase domains above and below a central domain, the activated CaMKII resembling a double-sided insect. Each kinase domain can phosphorylate a substrate, and thus encode one bit of synaptic information. Ordered arrays of bits are termed bytes, and 6 kinase domains on one side of each CaMKII can thus phosphorylate and encode calcium-mediated synaptic inputs as 6-bit bytes. But where is the intra-neuronal substrate for memory encoding by CaMKII phosphorylation? Enter microtubules.

Using molecular modeling, Craddock et al reveal a perfect match among spatial dimensions, geometry and electrostatic binding of the insect-like CaMKII, and hexagonal lattices of tubulin proteins in microtubules. They show how CaMKII kinase domains can collectively bind and phosphorylate 6-bit bytes, resulting in hexagonally-based patterns of phosphorylated tubulins in microtubules. Craddock et al calculate enormous information capacity at low energy cost, demonstrate microtubule-associated protein logic gates, and show how patterns of phosphorylated tubulins in microtubules can control neuronal functions by triggering axonal firings, regulating synapses, and traversing scale.

Microtubules and CaMKII are ubiquitous in eukaryotic biology, extremely rich in brain neurons, and capable of connecting membrane and cytoskeletal levels of information processing. Decoding and stimulating microtubules could enable therapeutic intervention in a host of pathological processes, for example Alzheimer’s disease in which microtubule disruption plays a key role, and brain injury in which microtubule activities can repair neurons and synapses.

Hameroff, senior author on the study, said: “Many neuroscience papers conclude by claiming their findings may help understand how the brain works, and treat Alzheimer’s, brain injury and various neurological and psychiatric disorders. This study may actually do that. We may have a glimpse of the brain’s biomolecular code for memory.”

Provided by University of Arizona

Source: medicalxpress.com

ScienceDaily (Mar. 8, 2012) — The hair cells of the inner ear have a previously unknown “root” extension that may allow them to communicate with nerve cells and the brain to regulate sensitivity to sound vibrations and head position, researchers at the University of Illinois at Chicago College of Medicine have discovered.

Type 2 hair cell with hair cell rootlets ending as expected in the cuticular plate. (Credit: Copyright University of Illinois Board of Trustees/Artist, Anna Lysakowski)

Their finding is reported online in advance of print in the Proceedings of the National Academy of Sciences.

The hair-like structures, called stereocilia, are fairly rigid and are interlinked at their tops by structures called tip-links.

When you move your head, or when a sound vibration enters your ear, motion of fluid in the ear causes the tip-links to get displaced and stretched, opening up ion channels and exciting the cell, which can then relay information to the brain, says Anna Lysakowski, professor of anatomy and cell biology at the UIC College of Medicine and principal investigator on the study.

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ScienceDaily (Mar. 8, 2012) — In both animals and humans, vocal signals used for communication contain a wide array of different sounds that are determined by the vibrational frequencies of vocal cords. For example, the pitch of someone’s voice, and how it changes as they are speaking, depends on a complex series of varying frequencies. Knowing how the brain sorts out these different frequencies — which are called frequency-modulated (FM) sweeps — is believed to be essential to understanding many hearing-related behaviors, like speech. Now, a pair of biologists at the California Institute of Technology (Caltech) has identified how and where the brain processes this type of sound signal.

This diagram shows areas in the midbrain region where direction- selective neurons were found. (Credit: Guangying Wu/Caltech)

Their findings are outlined in a paper published in the March 8 issue of the journal Neuron.

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ScienceDaily (Mar. 8, 2012) — A new study led by the Neuroscience Institute of Alicante reveals how manipulating the endocannabinoid system can modulate high levels of impulsivity. This is the main problem in psychiatric illnesses such a schizophrenia, bipolar disorder and substance abuse.

Spanish researchers have for the first time demonstrated that the CB2 receptor, which has modulating functions in the nervous system, is involved in regulating impulsive behaviour.

"Such a result proves the relevance that manipulation of the endocannabinoid system can have in modulating high levels of impulsivity present in a wide range of psychiatric and neurological illness," explains Jorge Manzanares Robles, a scientist at the Alicante Neuroscience Institute and director of the study.

Carried out on mice, the study suggests the possibility of undertaking future clinical trials using drugs that selectively act on the CB2 and thus avoid the psychoactive effects deriving from receptor CB1 manipulation, whose role in impulsivity has already been proven.

However, the authors of the study published in the British Journal of Pharmacology remain cautious. Francisco Navarrete, lead author of the study, states that “it is still very early to be able to put forward a reliable therapeutic tool.”

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March 8, 2012

New research from the University of Calgary’s Hotchkiss Brain Institute shows that by using a CT scan (computerized tomography), doctors can predict which patients are at risk of continued bleeding in the brain after a stroke. This vital information will allow doctors to utilize the most powerful blood clotting medications for those with the highest risk.

One in three individuals will continue to accumulate blood in the brain from a leak in a small artery. Pooling blood in the brain has serious consequences, and could lead to disability or even death. Previously, doctors in emergency stroke situations could not discern whether or not a patient’s brain bleeding had stopped. Using CT scan images, researchers can now identify “spot signs” that are seen as a small area of contrast on the CT scan. This spot sign is the actual location of bleeding within an artery in the brain.

"Technology that has emerged has allowed us to see the brain’s blood flow system in exquisite detail to precisely identify the source of the problem," explains Dr. Andrew Demchuk, Professor in the departments of clinical neurosciences and radiology, and lead author of this study. "We are now at a point where we can harness this technology to develop better treatments for patients with a blockage or breakage in a brain artery. Ultimately this research will confirm when immediate treatment is necessary – essentially, as soon as you see the spot sign."

This research provides validation of a new imaging marker to identify patients that may need to be treated with clotting medications versus those that don’t. “We must be very careful when and to whom these drugs are administered because they are so powerful at forming clots. These drugs can cause clots not only where there are holes and leaks – but also in intact arteries –potentially causing stroke and heart attacks,” says Demchuk. “Therefore this CT scan selection is critical for targeting only those patients at highest risk of continued bleeding.”

Clinical trials have now begun to test powerful clotting drugs in these patients.

This University of Calgary-led “PREDICT” study was coordinated with researchers at the Universities of Ottawa and Toronto, along with collaboration amongst nine other centres around the world. Their results were published in the March 8th online edition of the prestigious journal Lancet Neurology.

Provided by University of Calgary

Source: medicalxpress.com

March 8, 2012

The left image shows GABA inhibitory neurons (labeled green) in the brain’s reward pathway. The right panel shows electrical activity of GABA inhibitory neuron in a saline-injected or methamphetamine (METH)-injected mouse. Activation of the GABA type B receptor normally silences electrical activity, but has no effect in a mouse 24 hours after a single injection of methamphetamine Credit: Courtesy of Kelly Tan and Claire Padgett, Salk Institute for Biological Studies

A single injection of cocaine or methamphetamine in mice caused their brains to put the brakes on neurons that generate sensations of pleasure, and these cellular changes lasted for at least a week, according to research by scientists at the Salk Institute for Biological Studies.

Their findings, reported March 7 in Neuron, suggest this powerful reaction to the drug assault may be a protective, anti-addiction response. The scientists theorize that it might be possible to mimic this response to treat addiction to these drugs and perhaps others, although more experiments are required to explore this possibility.

"It was stunning to discover that one exposure to these drugs could promote such a strong response that lasts well after the drug has left the body," says Paul Slesinger, an associate professor in the Clayton Foundation Laboratories for Peptide Biology. "We believe this could be the brain’s immediate response to counteract the stimulation of these drugs."

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ScienceDaily (Mar. 7, 2012) — While the thought of any type of surgery can be disconcerting, the thought of brain surgery can be downright frightening. But for people with a particular form of epilepsy, surgical intervention can literally be life-restoring.

A PET scan of a brain from a patient with epiepsy, between seizures. The red indicates healthy tissue. On the right side of the image, there is less red in the mesial temporal area. This is hypometabolism, reflecting decreased brain function in the area where seizures begin. (Credit: Image courtesy of University of California - Los Angeles)

Yet among people who suffer from what’s known as medically intractable epilepsy, in which seizures are resistant to drugs, only a small fraction will seek surgery, seeing it only as a last resort. As a result, they continue to suffer seizures year after year. They can’t drive, they can’t work and they lose cognitive function as the years pass. Premature death is not uncommon.

But a multi-center study led by researchers at UCLA shows that for people suffering from intractable temporal lobe epilepsy, the most common form of intractable epilepsy, early surgical intervention followed by antiepileptic drugs stopped their seizures, improved their quality of life and helped them avoid decades of disability.

The report appears in the March 7 edition of the Journal of the American Medical Association.

"In short, they got their lives back," said Dr. Jerome Engel, the study’s principal investigator and director of the UCLA Seizure Disorder Center.

But the frustration of Engel and his colleagues is this: Few patients are referred to them for surgical evaluation, and those who are have had epilepsy for an average of 22 years.

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ScienceDaily (Mar. 7, 2012) — Stimulating the brain with a weak electrical current is a safe and effective treatment for depression and could have other surprise benefits for the body and mind, a major Australian study of transcranial Direct Current Stimulation (tDCS) has found.

Medical researchers from the University of New South Wales (UNSW) and the Black Dog Institute have carried out the largest and most definitive study of tDCS and found up to half of depressed participants experienced substantial improvements after receiving the treatment.

A non-invasive form of brain stimulation, tDCS passes a weak depolarising electrical current into the front of the brain through electrodes on the scalp. Patients remain awake and alert during the procedure.

"We are excited about these results. This is the largest randomised controlled trial of transcranial direct current stimulation ever undertaken and, while the results need to be replicated, they confirm previous reports of significant antidepressant effects," said trial leader, Professor Colleen Loo, from UNSW’s School of Psychiatry.

The trial saw 64 depressed participants who had not benefited from at least two other depression treatments receive active or sham tDCS for 20 minutes every day for up to six weeks.

"Most of the people who went into this trial had tried at least two other antidepressant treatments and got nowhere. So the results are far more significant than they might initially appear — we weren’t dealing with people who were easy to treat," Professor Loo said.

Significantly, results after six weeks were better than at three weeks, suggesting the treatment is best applied over an extended period. Participants who improved during the trial were offered follow up weekly ‘booster’ treatments, with about 85 percent showing no relapse after three months.

"These results demonstrate that multiple tDCS sessions are safe and not associated with any adverse cognitive outcomes over time," Professor Loo said, adding tDCS is simple and cost effective to deliver, requiring a short visit to a clinic.

The study also turned up additional unexpected physical and mental benefits, including improved attention and information processing.

"One participant with a long-standing reading problem said his reading had improved after the trial and others commented that they were able to think more clearly.

"Another participant with chronic neck pain reported that the pain had disappeared during the trial. We think that is because tDCS actually changes the brain’s perception of pain. We believe these cognitive benefits are another positive aspect of the treatment worthy of investigation," Professor Loo said.

The researchers are now looking at an additional trial to include people with bipolar disorder, with early results from overseas suggesting tDCS is just as effective in this group.

Source: Science Daily