Yale School of Medicine and University of Crete School of Medicine researchers report in Cell April 20 the first evidence of a molecular mechanism that dynamically alters the strength of higher brain network connections.

This discovery may help the development of drug therapies for the cognitive deficits of normal aging, and for cognitive changes in schizophrenia, bipolar disorder, or attention deficit hyperactivity disorder (ADHD).

“Our data reveal how the brain’s arousal systems influence the cognitive networks that subserve working memory-which plays a key role in abstract thinking, planning, and organizing, as well as suppressing attention to distracting stimuli,” said http://info.med.yale.edu/neurobio/arnsten/arnsten.html Amy Arnsten, lead author and neurobiology professor at Yale.

The brain’s prefrontal cortex (PFC) normally is responsible for so-called executive functions. The ability of the PFC to maintain such memory-based functions declines with normal aging, is weakened in people with ADHD, and is severely disrupted in disorders such as schizophrenia and bipolar disorder.

The current study found that brain cells in PFC contain ion channels called hyperpolarization-activated cyclic nucleotide-gated channels (HCN) that reside on dendritic spines, the tiny protrusions on neurons that are specialized for receiving information. These channels can open when they are exposed to cAMP (cyclic adenosine monophosphate). When open, the information can no longer flow into the cell, and thus the network is effectively disconnected. Arnsten said inhibiting cAMP closes the channels and allows the network to reconnect.

The study also found alpha-2A adrenergic receptors near the channels that inhibit the production of cAMP and allow the information to pass through into the cell, connecting the network. These receptors are stimulated by a natural brain chemical norepinephrine or by medications like guanfacine.

“Guanfacine can strengthen the connectivity of these networks by keeping these channels closed, thus improving working memory and reducing distractibility,” she said. “This is the first time we have observed the mechanism of action of a psychotropic medication in such depth, at the level of ion channels.”

Arnsten said the excessive opening of HCN channels might underlie many lapses in higher cognitive function. Stress, for example, appears to flood PFC neurons with cAMP, which opens HCN channels, temporarily disconnects networks, and impairs higher cognitive abilities.

There is also evidence that this pathway may not be properly regulated with advancing age, resulting in destruction of cAMP. The dysregulation of the pathway may contribute to increased forgetfulness and susceptibility to distraction as we grow older.

The research is also relevant to common disorders such as ADHD, which is associated with weaker regulation of attention and behavior. ADHD is highly heritable, and some patients with ADHD may have genetic changes in molecules that weaken the production of norepinephrine. Treatments for ADHD all enhance stimulation of the norepinephrine receptors.

These new data also have important implications for the researchers’ studies of more severe mental illnesses like schizophrenia and bipolar disorder, which can involve mutations of a molecule called DISC1 (Disrupted in Schizophrenia) that normally regulates cAMP. Loss of function of DISC1 in patients with schizophrenia or bipolar disorder would increase vulnerability to cortical network disconnection and profound PFC deficits. This may be especially problematic during exposure to even mild stress, which may explain the frequent worsening of symptoms following exposure to stress. “We find it remarkable to relate a genetic mutation in patients to the regulation by an ion channel of PFC neuronal networks,” said Arnsten.

Co-authors include Min Wang, Brian Ramos, Yousheng Shu, Arthur Simen, Alvaro Duqye, Avis Brennan, Susheel Vijayraghavan, Anne Dudley, Eric Nou, David McCormick, James Mazer and Constantinos Paspalas, who also has an appointment at the University of Crete School of Medicine in Heraklion, Greece.

Source: Yale.

Scientists know little about how the brain assigns cells to participate in encoding and storing memories. Now a UCLA/University of Toronto team has discovered that a protein called CREB controls the odds of a neuron playing a role in memory formation. The April 20 edition of Science reports the findings, which suggest a new approach for preserving memory in people suffering from Alzheimer’s or other brain injury.

"Making a memory is not a conscious act," explained Alcino Silva, principal investigator and a professor of neurobiology and psychiatry at the David Geffen School of Medicine at UCLA. "Learning triggers a cascade of chemicals in the brain that influence which memories are kept and which are lost.

"Earlier studies have linked the CREB protein to keeping memories stable," added Silva, a member of the UCLA Brain Research Institute. "We suspected it also played a key role in channeling memories to brain cells that are ready to store them."

Silva and his colleagues used a mouse model to evaluate their hypothesis. They implanted CREB into a virus, which they introduced into some of the cells in the animal’s amygdala, a brain region critical to emotional memory.

Next they tested the mouse’s ability to recall a specific cage it had visited before. The cage was outfitted with patterned walls and a unique smell.

To visualize which brain cells stored the mouse’s memories about the cage, the scientists tracked a genetic marker that reveals recent neuron activity. When the team examined the animals’ amygdalas after the experiment, they found substantial amounts of CREB and the marker in neurons.

"We discovered that the amount of CREB influences whether or not the brain stores a memory," said Silva. "If a cell is low in CREB, it is less likely to keep a memory. If the cell is high in CREB, it is more likely to store the memory."

Human implications of the new research could prove profound.

"By artificially manipulating CREB levels among groups of cells, we can determine where the brain stores its memories," he explained. "This approach could potentially be used to preserve memory in people suffering from Alzheimer’s or other brain injury. We may be able to guide memories into healthy cells and away from sick cells in dying regions of the brain."

Our memories define who we are, so learning how the brain stores memory is fundamental to understanding what it is to be human, Silva observed.

"A memory is not a static snapshot," he said. "Memories serve a purpose. They are about acquiring information that helps us deal with similar situations in the future. What we recall helps us learn from our past experiences and better shape our lives."

Silva’s coauthors included Steven Kushner and Robert Brown of UCLA; Sheena Josselyn, Jin-Hee Han, Adelaide Yiu and Christy Cole of the University of Toronto; Rachel Neve of Harvard University; and John Guzowski of UC Irvine.

Source: UCLA

What it is: Roll your mouse over the glowing orbs and mix some music!

The Spacializer Widget represents multiple sound samples, each as a luminescent orb of color. The volume of each sample varies depending upon how close your mouse pointer is to the associated colored orb.

Keep your visitors at your blog by giving them a diversion in between reading your posts!

How to Load it: Just unzip the directory into your wordpress ‘plugins’ directory and it ought to work just fine.

Below you’ll see how I’ve included it on my blog in the past.

Download the Spacializer Widget v.4 here.

Autistic children are able to interpret the mental state of others by looking at their eyes, contrary to previous research, a new University of Nottingham study has found.

In findings that contradict previous studies, psychologists found that autistic children can ‘read’ a stranger’s mental state based on that person’s eyes. Autistic children have long been thought to be poor at interpreting people’s mental states based on facial expressions, especially expressions around the eyes.

Some researchers believe that this lack of ability could be central to the social problems experienced by autistic children and adults.

But the latest findings cast doubt on this hypothesis. A study at The University of Nottingham found that autistic children were able to interpret mental states when looking at animated facial expressions. The findings also suggest that the use of moving images, rather than conventional still pictures, gives a much more accurate measure of the abilities of autistic children.

Researchers hope that by increasing understanding of autism, their findings may ultimately help in the teaching and treatment of people with the condition.

Published in the latest issue of the journal Child Development, the study was led by Dr Elisa Back. Her co-researchers were Professor Peter Mitchell and Dr Danielle Ropar of the School of Psychology at The University of Nottingham.

Dr Back said: “Previous findings show that children and adolescents with autism may have difficulty reading mental states from facial expressions but our results suggest that this is not due to an inability to interpret information from the eyes.

“Surprisingly, autistic children seemed particularly reliant on the eyes and also the mouth when making mentalistic inferences.

“The conclusions of previous research are largely based on methods that present static photographs to participants. Our study indicates that a more accurate measure of the abilities of those with autism can be obtained through the use of sophisticated digital imaging techniques with animated facial expressions.”

The study compared two groups of autistic children, one group aged 10-14 and one aged 11-15, with two control groups of non-autistic children. They underwent a series of tests to see whether they could gauge the mental state of a stranger by looking at different parts of the face.

Researchers conducted two experiments in which the participants looked at a series of facial expressions on a laptop screen. In the facial images used, the eyes and mouth were either ‘freeze-framed’ in a neutral expression, or animated and expressive. By showing a sequence of different combinations, they were able to gauge which aspects of the face were used by the autistic children to ‘read’ someone’s mental state - and how successful they were.

In the second experiment, the 18 autistic children involved were as successful as non-autistic children in interpreting mental states, whether they saw the eyes in isolation or in the context of the whole face. This indicates that autistic children do, in fact, make use of information from the eyes - a finding that contradicts prior studies.

An estimated 588,000 people have autism in the UK, according to the National Autistic Society. A mental health survey by the Office for National Statistics found the prevalence of children and young people anywhere on the autistic spectrum is 0.9 per cent - almost one in every 100.