neurosciencestuff:

The World’s Most Famous Brain

In the summer of 1953, Henry Gustav Molaison (1926-2008) underwent brain surgery to contain epileptic seizures that had become critically debilitating. The intervention brought some relief from convulsions, but these positive results were overshadowed by an astonishing and indelible side effect. Soon after the operation, it became apparent that he could no longer recognize hospital staff, he did not remember the way home, he did not remember newspaper articles he had just read, nor the crossword puzzles he had solved; otherwise, he was completely normal. Since the time of the surgery, more than five decades of scrupulous neuropsychological research examined the nature of patient H.M.’s amnesia which proved to be both persistent and remarkably selective.

The goal of our project is to provide a window into the brain of the man who helped establish the scientific study of memory and unfailingly forgot the enormously generous contribution he made to medical research.


How the Brain and Nerve Cells Change During Alzheimer’s Disease
One of the hallmarks of Alzheimer’s disease is the accumulation of amyloid plaques between nerve cells (neurons) in the brain. Beta amyloid is a fragment of a protein snipped from another protein called amyloid precursor protein (APP). In a healthy brain, these protein fragments would break down and be eliminated. In Alzheimer’s disease, the fragments accumulate to form hard, insoluble plaques.
Neurofibrillary tangles are insoluble twisted fibers found inside the brain’s nerve cells. They primarily consist of a protein called tau, which forms part of a structure called a microtubule. The microtubule helps transport nutrients and other important substances from one part of the nerve cell to another. Axons are long threadlike extensions that conduct nerve impulses away from the nerve cell; dendrites are short branched threadlike extensions that conduct nerve impulses towards the nerve cell body. In Alzheimer’s disease the tau protein is abnormal and the microtubule structures collapse.
As Alzheimer’s disease spreads through the cerebral cortex (the outer layer of the brain), judgment worsens, emotional outbursts may occur and language is impaired. Memory worsens and may become almost non-existent. On average, those with Alzheimer’s live for 8 to 10 years after diagnosis, but this terminal disease can last for as long as 20 years.

How the Brain and Nerve Cells Change During Alzheimer’s Disease

One of the hallmarks of Alzheimer’s disease is the accumulation of amyloid plaques between nerve cells (neurons) in the brain. Beta amyloid is a fragment of a protein snipped from another protein called amyloid precursor protein (APP). In a healthy brain, these protein fragments would break down and be eliminated. In Alzheimer’s disease, the fragments accumulate to form hard, insoluble plaques.

Neurofibrillary tangles are insoluble twisted fibers found inside the brain’s nerve cells. They primarily consist of a protein called tau, which forms part of a structure called a microtubule. The microtubule helps transport nutrients and other important substances from one part of the nerve cell to another. Axons are long threadlike extensions that conduct nerve impulses away from the nerve cell; dendrites are short branched threadlike extensions that conduct nerve impulses towards the nerve cell body. In Alzheimer’s disease the tau protein is abnormal and the microtubule structures collapse.

As Alzheimer’s disease spreads through the cerebral cortex (the outer layer of the brain), judgment worsens, emotional outbursts may occur and language is impaired. Memory worsens and may become almost non-existent. On average, those with Alzheimer’s live for 8 to 10 years after diagnosis, but this terminal disease can last for as long as 20 years.

Understanding Bipolar disorder

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Bipolar disorder (also known as manic depression) causes serious shifts in mood, energy, thinking, and behavior–from the highs of mania on one extreme, to the lows of depression on the other. More than just a fleeting good or bad mood, the cycles of bipolar disorder last for days, weeks, or months. And unlike ordinary mood swings, the mood changes of bipolar disorder are so intense that they interfere with your ability to function.

There are four types of mood episodes in bipolar disorder: mania, hypomania, depression, and mixed episodes.

Common signs and symptoms of mania:

·         Feeling unusually “high” and optimistic OR extremely irritable

·         Unrealistic, grandiose beliefs about one’s abilities or powers

·         Sleeping very little, but feeling extremely energetic

·         Talking so rapidly that others can’t keep up

·         Racing thoughts; jumping quickly from one idea to the next

·         Highly distractible, unable to concentrate

·         Impaired judgment and impulsiveness

·         Acting recklessly without thinking about the consequences

·         Delusions and hallucinations (in severe cases)

Common signs and symptoms of hypomania

Hypomania is a less severe form of mania. People in a hypomanic state feel euphoric, energetic, and productive, but they are able to carry on with their day-to-day lives and they never lose touch with reality. To others, it may seem as if people with hypomania are merely in an unusually good mood. However, hypomania can result in bad decisions that harm relationships, careers, and reputations. In addition, hypomania often escalates to full-blown mania or is followed by a major depressive episode.

Common symptoms of bipolar depression:

·         Feeling hopeless, sad, or empty.

·         Irritability

·         Inability to experience pleasure

·         Fatigue or loss of energy

·         Physical and mental sluggishness

·         Feeling hopeless, sad, or empty.

·         Irritability

·         Inability to experience pleasure

·         Fatigue or loss of energy

·         Physical and mental sluggishness

Common signs and symptoms of a mixed episode

A mixed episode of bipolar disorder features symptoms of both mania or hypomania and depression. For example, depression combined with agitation, irritability, anxiety, insomnia, distractibility, and racing thoughts. This combination of high energy and low mood makes for a particularly high risk of suicide.

Bipolar disorder has no single cause. It appears that certain people are genetically predisposed to bipolar disorder. Yet not everyone with an inherited vulnerability develops the illness, indicating that genes are not the only cause. Some brain imaging studies show physical changes in the brains of people with bipolar disorder. Other research points to neurotransmitter imbalances, abnormal thyroid function, circadian rhythm disturbances, and high levels of the stress hormone cortisol. External environmental and psychological factors are also believed to be involved in the development of bipolar disorder.

Source: http://www.helpguide.org/mental/bipolar_disorder_symptoms_treatment.htm

notalwaysred:

Harvard scientists map the inside of the human brain as a magnetic resonance scanner builds the first 3D interior maps of the brain

wildcat2030:

The left-brain right-brain myth will probably never die because it has become a powerful metaphor for different ways of thinking – logical, focused and analytic versus broad-minded and creative. Take the example of Britain’s Chief Rabbi Jonathan Sacks talking on BBC Radio 4 earlier this year. “What made Europe happen and made it so creative,” he explained, “is that Christianity was a right-brain religion … translated into a left-brain language [Greek]. So for many centuries you had this view that science and religion are essentially part of the same thing.” As well as having metaphorical appeal, the seductive idea of the right brain and its untapped creative potential also has a long history of being targeted by self-help gurus peddling pseudo-psychology. Today the same idea is also picked up by the makers of self-improvement video games and apps. The latest version of the The Faces iMake-Right Brain Creativity app for the Ipad, for example, boasts that it is “an extraordinary tool for developing right brain creative capabilities”.

Probing the roots of depression by tracking serotonin regulation at a new level

neurosciencestuff:

June 28, 2012

In a process akin to belling an infinitesimal cat, scientists have managed to tag a protein that regulates the neurotransmitter serotonin with tiny fluorescent beads, allowing them to track the movements of single molecules for the first time.

This is a microphotograph of neurons with their serotonin transporter protein labeled with red quantum dots. Credit: Jerry Chang, Vanderbilt University

The capability, which took nearly a decade to achieve, makes it possible to study the dynamics of serotonin regulation at a new level of detail, which is important because of the key role that serotonin plays in the regulation of mood, appetite and sleep.

The achievement was reported by an interdisciplinary team of Vanderbilt scientists in the June 27 issue of the Journal of Neuroscience.

The regulatory protein that the scientists successfully tagged is known as the serotonin transporter. This is a protein that extends through the membrane that forms the nerve’s outer surface and acts like a nano-sized vacuum cleaner that sucks serotonin molecules into the cell body and away from serotonin target receptors on other cells. In this fashion it helps regulate the concentration of serotonin in the area around the cell. Serotonin transporters are an important research subject because they are the target for the most common drugs used to treat depression, including Prozac, Paxil and Lexapro.

“If you are interested in mental health, then serotonin transporters are an ideal subject,” said Sandra Rosenthal, the Jack and Pamela Egan Chair of Chemistry, who directed the study with Randy Blakely, the Allan D. Bass Professor of Pharmacology and Psychiatry.

Problems with serotonin transporter regulation have also been implicated in autism. Two years ago, Blakely and geneticist James Sutcliffe, associate professor of molecular physiology and biophysics, reported the discovery of multiple changes in the serotonin transporter protein that cause the transporter to become “overactive” in subjects with autism. Recently, Blakely and Assistant Professor of Psychiatry Jeremy Veenstra-VanderWeele reported that mice expressing one of these high-functioning transporters exhibit multiple behavioral changes that resemble changes seen in kids with autism.

The brain’s other key neurotransmitters have their own transporter proteins, so scientists can use the capability to track the motion of individual transporter molecules to determine how they are regulated as well.

Attempts to understand how these transporters work have been limited by the difficulty of studying their dynamic behavior. “In the past, we have been limited to snapshots that show the location of transporter molecules at a specific time,” said chemistry graduate student Jerry Chang, who developed the tagging technique. “Now we can follow their motion on the surface of cells in real time and see how their movements relate to serotonin uptake activity.”

The fluorescent tags that the researchers used are nanoscale beads called quantum dots made from a mixture of cadmium and selenium. These beads are only slightly bigger than the proteins they are tagging: You would have to string 10,000 together to span the width of a human hair.

Quantum dots emit colored light when illuminated and have the useful property that small changes in their size cause them to glow in different colors. Team member Ian D. Tomlinson, assistant research professor of chemistry, developed a special molecular string that attaches to the quantum dot at one end and, on the other end, attaches to a drug derivative that binds exclusively with the serotonin transporter. When a mixture that contains these quantum dots is incubated with cultured nerve cells, the drug attaches to the transporter. As the protein moves around, it drags the quantum dot behind it like a child holding a balloon on a string. When the area is illuminated, the quantum dots show up in a microscope as colored points of light.

“Until now, neurobiologists have had to rely on extremely low resolution approaches where it takes the signals coming from thousands to millions of molecules to be detected,” said Blakely, “We really had no idea exactly what we were going to see.”

Putting their new procedure to use, the researchers looked at extensions of the nerve cell that are involved in secreting serotonin on the presumption that transporters would be localized there as well. From previous research, the investigators suspected that the transporters would be concentrated in cholesterol-rich parts of these extensions, termed rafts, although the level of resolution with standard approaches was inadequate to provide any clues as to what they were doing there.

The quantum dot studies demonstrated that there were two distinct populations of transporters in these areas: Those that can travel freely around the membrane and those that act as if they are unable to move. They found that the immobile transporters were located in the rafts. When they stimulated the cell to increase transporter activity, they were surprised at what happened. “We found that the transporters in the rafts began to move much faster whereas the motion of the other population didn’t change at all,” Rosenthal reported. Since the mobilized transporters do not leave the rafts, they appear to whizz around inside a confined compartment, as if released from chains that normally keep them subdued. These observations suggest it is likely that the two populations are controlled by different regulatory pathways.

“Now that we can watch transporter regulation actually happening, we should be able to figure out the identity of the anchoring proteins and the signals these proteins respond to that permit transporters to switch back and forth between low and high activity levels,” said Blakely.

“Currently, antidepressant drugs must fully shut down the brain’s serotonin transporters to achieve a clinical benefit,” the pharmacologist said. Such a manipulation can produce a number of unpleasant side-effects, such as nausea, weight gain, sexual problems, fatigue and drowsiness.

“By understanding the basic mechanisms that naturally turn serotonin transporter activity up and down, maybe we can develop medications that produce milder side-effects and have even greater efficacy,” he said. “Our sights are also focused on transferring what we have learned with normal serotonin transporters to an understanding of the hyperactive transporters we have found in kids with autism.”

Provided by Vanderbilt University

Source: medicalxpress.com

Balancing connections for proper brain function

neurosciencestuff:

June 22, 2012

Neuropsychiatric conditions such as autism, schizophrenia and epilepsy involve an imbalance between two types of synapses in the brain: excitatory synapses that release the neurotransmitter glutamate, and inhibitory synapses that release the neurotransmitter GABA. Little is known about the molecular mechanisms underlying development of inhibitory synapses, but a research team from Japan and Canada has reported that a molecular signal between adjacent neurons is required for the development of inhibitory synapses.

Figure 1: Compared with the brains of normal animals (left), mice lacking the Slitrk3 gene (right) have a reduced density of inhibitory synapses in the hippocampus. Reproduced from Ref. 1 © 2012 Jun Aruga, RIKEN Brain Science Institute

In earlier work, the researchers—led by Jun Aruga of the RIKEN Brain Science Institute, Wako, and Ann Marie Craig of the University of British Colombia, Vancouver—showed that a membrane protein called Slitrk2 organizes signaling molecules at synapses. They therefore tested whether five related proteins are involved in inhibitory synapse development. They cultured immature hippocampal neurons with non-neural cells expressing each of the six Slitrk proteins. They found that Slitrk3, but not other Slitrk proteins, induced clustering of VGAT, a GABA transporter protein found only at inhibitory synapses.

The researchers also examined the localization of Slitrk3 by tagging it with yellow fluorescent protein and introducing it into cultured hippocampal cells. This revealed that Slitrk3 co-localizes in the dendrites of neurons with gephyrin, a scaffold protein found only in inhibitory synapses. They then blocked Slitrk3 synthesis, and found that it led to a significant reduction in the number of inhibitory synapses.

To confirm these findings, the researchers generated a strain of genetically engineered mice lacking the Slitrk3 gene. These animals had significantly fewer inhibitory synapses than normal animals (Fig. 1), and therefore impaired neurotransmission of GABA. They were also susceptible to epileptic seizures. From a screen for proteins that bind to Slitrk3, Aruga, Craig and colleagues identified the protein PTPδ as its only binding partner. Introduction of PTPδ fused to yellow fluorescent protein to cultured hippocampal neurons showed that it is expressed in neuronal dendrites and cell bodies, but not in axons. Blocking PTPδ synthesis prevented the induction of inhibitory synapses by the Slitrk3 protein.

These results demonstrated that the interaction between Slitrk3 on dendrites and PTPδ on axons of adjacent cells is required for the proper development of inhibitory synapses and for inhibitory neurotransmission in the brain.

“We are now examining whether the balance of excitatory and inhibitory synapses is affected by other members of the Slitrk protein family,” says Aruga. “It is possible that Slitrk3 and other Slitrk proteins are acting synergistically or antagonistically. We are also clarifying whether Slitrk3 is involved in any neurological disorders.”

Provided by RIKEN

Source: medicalxpress.com

Where is the Love?

neurosciencestuff:

June 21, 2012 By Janice Wood

Thanks to science, we know that love lives in the brain, not the heart.

Now a new international study has mapped out where love and sexual desire are in the brain.

“No one has ever put these two together to see the patterns of activation,” says Dr. Jim Pfaus, professor of psychology at Concordia University.

“We didn’t know what to expect –the two could have ended up being completely separate. It turns out that love and desire activate specific but related areas in the brain.”

Working with colleagues in the United States and Switzerland, Pfaus analyzed the results of 20 separate studies that examined brain activity while subjects engaged in tasks such as viewing erotic pictures or looking at photographs of their significant others. Pooling this data enabled the scientists to form a map of love and desire in the brain.

They found that two brain structures, the insula and the striatum, are responsible for tracking the progression from sexual desire to love.

The insula is a portion of the cerebral cortex folded deep within an area between the temporal lobe and the frontal lobe, while the striatum is located nearby, inside the forebrain.

According to the researchers, love and sexual desire activate different areas of the striatum. The area activated by sexual desire is usually turned on by things that are inherently pleasurable, such as sex or food.

The area activated by love is involved in the process of conditioning in which things paired with reward or pleasure are given inherent value. That is, as feelings of sexual desire develop into love, they are processed in a different place in the striatum, the researchers explain.

This area of the striatum is also the part of the brain associated with drug addiction. Pfaus says there is good reason for this.

“Love is actually a habit that is formed from sexual desire as desire is rewarded,” he explains. “It works the same way in the brain as when people become addicted to drugs.”

However, the habit is not a bad one, he said, noting that love activates different pathways in the brain that are involved in monogamy and pair bonding. Some areas in the brain are actually less active when a person feels love than when they feel desire, he added.

“While sexual desire has a very specific goal, love is more abstract and complex, so it’s less dependent on the physical presence someone else,” says Pfaus.

Source: PsychCentral

fuckyeahmolecularbiology:

Meet Phineas Gage, more commonly known as neuroscience’s most intriguing case.

On September 18th, 1848, the unfortunate 25-year-old railroad worker was using an iron rod to tamp down blasting powder when it exploded, sending the 43-inch-long, 13-pound cylinder through his left cheek and out the top of his head.

While the accident was certainly ghastly, what baffled scientists was both Gage’s survival, and, even stranger, his profound personality changes following the incident. John Harlow, a doctor who treated the once-affable Gage, wrote that he “could not stick to plans, uttered ‘the grossest profanity’ and showed ‘little deference for his fellows,’” as reported by Smithsonian magazine in 2010. Through the remainder of his life, Gage worked at a stable in New Hampshire and then as a stagecoach driver in Chile before moving to San Francisco. He died there after a series of seizures 12 years after the accident.

Even now, 152 years after Gage’s death, he still remains intriguing to neuroscientists - so intriguing, in fact, that his head is prompting a new wave of research. In a new study, published in the May 16 issue of the journal PLoS One, scientists at UCLA used brain-mapping data from computed tomography (CT) and magnetic resonance imaging (MRI) scans to determine the specific damage inflicted on the neurological “pathways” in Gage’s brain.

“What we found was a significant loss of white matter connecting the left frontal regions and the rest of the brain,” said study co-author Jack Van Horn, an assistant professor of neurology at UCLA. “We suggest that the disruption of the brain’s ‘network’ considerably compromised it [the white matter]. This may have had an even greater impact on Mr. Gage than the damage to the cortex alone in terms of his purported personality change.”

Only about 4% of Gage’s cerebral cortex was directly affected by the rod, the study showed. But more than 10 percent of the white matter was damaged. The white matter is the fatty tissue within the brain that coordinates communication between its different regions.

In addition to helping explain Gage’s deterioration, the study showcases the power of brain mapping - a technology that neurologists believe will lead eventually to an understanding of the links between the brain’s “wiring” and specific mental disorders. Even more intriguingly, the study managed to draw parallels between Gage’s case and several modern neurological traumas, including Alzheimer’s disease.

He may have died in 1860, but I have a feeling that we haven’t seen the last of Phineas Gage - or his ghastly accident’s lasting contributions to modern neuroscience.

For more information on Gage and the study, check out the PopSci article here.

Upper image: A computer-generated 3D rendering of the iron rod through Gage’s brain as estimated from his skull (which is on display at Warren Anatomical Museum in Boston, along with the tamping rod).

Lower Images: Left, a circular representation of cortical anatomy and WM connectivity in a normal 25 to 36-year-old male. Right, the mean connectivity affected by the presence of the tamping iron combined across subjects. (And an estimate of Gage’s neural connectivity).

Ear delivers sound information to brain in surprisingly organized fashion: study

neurosciencestuff:

June 5, 2012

The brain receives information from the ear in a surprisingly orderly fashion, according to a University at Buffalo study scheduled to appear June 6 in the Journal of Neuroscience.

Light microscope image of a bushy neuron in the cochlear nucleus, with a glass microelectrode for recording electrical activity inside the cell. The cell is about 12 micrometers in diameter. New research, published in the Journal of Neuroscience, shows that the synapses onto these cells are sorted according to their plasticity. Credit: Dr. L. Pliss

The research focuses on a section of the brain called the cochlear nucleus, the first way-station in the brain for information coming from the ear. In particular, the study examined tiny biological structures called synapses that transmit signals from the auditory nerve to the cochlear nucleus.

The major finding: The synapses in question are not grouped randomly. Instead, like orchestra musicians sitting in their own sections, the synapses are bundled together by a key trait: plasticity.

Plasticity relates to how quickly a synapse runs down the supply of neurotransmitter it uses to send signals, and plasticity can affect a synapse’s sensitivity to different qualities of sound. Synapses that unleash supplies rapidly may provide good information on when a sound began, while synapses that release neurotransmitter at a more frugal pace may provide better clues on traits like timbre that persist over the duration of a sound.

UB Associate Professor Matthew Xu-Friedman, who led the study, said the findings raise new questions about the physiology of hearing. The research shows that synapses in the cochlear nucleus are arranged by plasticity, but doesn’t yet explain why this arrangement is beneficial, he said.

“It’s clearly important, because the synapses are sorted based on this. What we don’t know is why,” said Xu-Friedman, a member of UB’s Department of Biological Sciences. “If you look inside a file cabinet and find all these pieces of paper together, you know it’s important that they’re together, but you may not know why.”

In the study, Xu-Friedman and Research Assistant Professor Hua Yang used brain slices from mice to study about 20 cells in the cochlear nucleus called bushy cells, which receive information from synapses attached to auditory nerve fibers.

The experiments revealed that each bushy cell was linked to a network of synapses with similar plasticity. This means that bushy cells themselves may become specialized, developing unique sensitivities to particular characteristics of a sound, Xu-Friedman said.

The study hints that the cochlear nucleus may not be the only part of the brain where synapses are organized by plasticity. The researchers observed the phenomenon in the excitatory synapses of the cerebellum as well.

“One reason this may not have been noticed before is that measuring the plasticity of two different synapses onto one cell is technically quite difficult,” Xu-Friedman said.

Provided by University at Buffalo

Source: medicalxpress.com