SPEEDY EXPANSION OF HUMAN APE CEREBELLUM

A new study published in the Cell Press journal Current Biology on October 2 could rewrite the story of ape and human brain evolution. While the neocortex of the brain has been called "the crowning achievement of evolution and the biological substrate of human mental prowess," newly reported evolutionary rate comparisons show that the cerebellum expanded up to six times faster than anticipated throughout the evolution of apes, including humans.

The findings suggest that technical intelligence was likely at least as important as social intelligence in human cognitive evolution, the researchers say.

"Our results highlight a previously unappreciated role of the cerebellum in ape and human brain evolution that has the potential to refocus researchers' thinking about how and why the brains in these species have become distinct and to shift attention away from an almost exclusive focus on the neocortex as the seat of our humanity," says Robert Barton of Durham University in the United Kingdom.

The cerebellum had been seen primarily as a brain region involved in movement control, adds Chris Venditti of the University of Reading. But more recent evidence has begun to suggest that the cerebellum has a broader range of functions. The cerebellum also contains an intriguingly large number of densely packed neurons.

"In humans, the cerebellum contains about 70 billion neurons -- four times more than in the neocortex," Barton says. "Nobody really knows what all these neurons are for, but they must be doing something important."

The neocortex had gotten most of the attention in part because it is such a large structure to begin with. As a result, in looking at variation in the size of various brain regions, the neocortex appeared to show the most expansion. But much of that increase in size could be explained away by the size of the animal as a whole. Sperm whales have a neocortex that is proportionally larger than that of humans, for example.

By using a comparative method that controlled for those differences in the way the two brain structures correlate, Barton and Venditti uncovered a striking pattern: both nonhuman apes and humans depart from the otherwise tight correlation in size between the cerebellum and neocortex found across other primates due to relatively rapid evolutionary expansion of the cerebellum.

Barton and Venditti say that the cerebellum seems to be particularly involved in the temporal organization of complex behavioral sequences, such as those involved in making and using tools, for instance. Interestingly, evidence is now emerging for a critical role of the cerebellum in language, too.

While plenty of work remains, the new study establishes the cerebellum as "a new frontier for investigations into the neural basis of advanced cognitive abilities," the researchers say.

Prion Proteins The Sci Fi Villains Behind Mad Cow Disease And Human Chronic Nerve Problems

Today's post from media.uzh.ch (see link below) may seem light years away from the sorts of neuropathy we experience every day but in fact is much closer than you think. With all these things, you have to continually remind yourself exactly what neuropathy is:- damage to the nerves. There are dozens of causes and dozens of types but nerve damage leads to the symptoms we most frequently feel. This fascinating article brings images from the 90's of cows struggling to stay on their feet under the same general umbrella description as the tingling and burning we suffer from when we report our symptoms to our doctors. Scientists are seemingly just beginning to scratch the surface of the knowledge that concludes that certain proteins can be responsible for all this strange behaviour in our nervous systems. It's fascinating and frightening at the same time but you do get the feeling that we're on the point of huge scientific discoveries regarding neuropathy and that can only be a good thing as we struggle with drug treatments that clearly only work to a limited extent. Worth a read - fascinating stuff!

Impact of prion proteins on the nerves revealed for the first time
News release, 8 August 2016 
 
When prion proteins mutate, they trigger mad cow and Creutzfeldt-Jakob disease. Although they are found in virtually every organism, the function of these proteins remained unclear. Researchers from the University of Zurich and the University Hospital Zurich now demonstrate that prion proteins, coupled with a particular receptor, are responsible for nerve health. The discovery could yield novel treatments for chronic nerve diseases.


Without the prion proteins, the so-called Schwann cells around the sensitive nerve fibers no longer form an insulating layer to protect the nerves. (Image: NatureReview / Neuroscience)

Ever since the prion gene was discovered in 1985, its role and biological impact on the neurons has remained a mystery. “Finally, we can ascribe a clear-cut function to prion proteins and reveal that, combined with particular receptor, they are responsible for the long-term integrity of the nerves,” says Professor Adriano Aguzzi from the Neuropathological Institute at the University of Zurich and University Hospital Zurich. The present study therefore clears up a question that researchers have been puzzling over for 30 years, but ultimately went unanswered.

Prions are dangerous pathogens that trigger fatal brain degeneration in humans and animals. In the 1990s, they were responsible for the BSE epidemic more commonly known as mad cow disease. In humans, they cause Creutzfeldt-Jakob disease and other neurological disorders that are fatal and untreatable. Meanwhile, we know that infectious prions consist of a defectively folded form of a normal prion protein called PrPC located in the neuron membrane. The infectious prions multiply by kidnapping PrPC and converting it into other infectious prions. 

Absent prion proteins cause nerve diseases

For a long time, it remained unclear why we humans – like most other organisms – have a protein in our neurons that does not perform any obvious function, yet can be extremely dangerous. Aguzzi has spent decades researching this issue and examining the theory that animals without the PrPC gene are resistant to prion diseases. But what are the repercussions for the organism if the prion protein is deactivated?

A few years ago, Aguzzi and his team discovered that mice without the PrPC gene suffer from a chronic disease of the peripheral nervous system. The reason: The so-called Schwann cells around the sensitive nerve fibers no longer form an insulating layer to protect the nerves. Due to this insulating myelin deficit, the peripheral nerves become diseased, potentially resulting in motoric disorders in the motion tract and paralysis.

The researchers have now gone one step further in the lab: In a new study, Alexander Küffer and Asvin Lakkaraju clarify exactly why the peripheral nerves become damaged in the absence of the prion protein PrPC. They discovered how the PrPC produced by the neurons docks onto the Schwann cells: namely via a receptor called Gpr126. If the prion protein and the receptor work together, a particular messenger substance (cAMP) which regulates the chemical interaction in the cells and is essential for the integrity of the nerve’s protective sheath increases. Gpr126 belongs to the large family of “G-protein-coupled receptors”, which are involved in many physiological processes and diseases.

30-year-old research question finally answered

This discovery solves a key question that has long puzzled neuroscientists and points towards future applications in hospitals. “If you want to deactivate the prion protein PrPC fully for potential Creutzfeld-Jakob disease treatments, you need to know the potential side effects on the nerves in the future,” explains Aguzzi. Moreover, the present results on the effect of PrPC at molecular level could yield a new approach for peripheral neuropathy. Currently, there are only extremely limited therapeutic options for these chronic debilitating diseases of the nervous system.
Literature:

Alexander Küffer, Asvin K. K. Lakkaraju, Amit Mogha, Sarah C. Petersen, Kristina Airich, Cédric Doucerain, Rajlakshmi Marpakwar, Pamela Bakirci, Assunta Senatore, Arnaud Monnard, Carmen Schiavi, Mario Nuvolone, Bianka Grosshans, Simone Hornemann, Frederic Bassilana, Kelly R. Monk & Adriano Aguzzi. The prion protein is an agonistic ligand of the G-protein-coupled receptor Gpr1/Adgrg6. Nature, 8 August 2016. doi:10.1038/nature19312

http://www.media.uzh.ch/en/Press-Releases/2016/Prion-Proteine.html

NON CODING HALF OF HUMAN GENOME UNLOCKED WITH NOVEL SEQUENCING TECHNIQUE

An obscure swatch of human DNA once thought to be nothing more than biological trash may actually offer a treasure trove of insight into complex genetic-related diseases such as cancer and diabetes, thanks to a novel sequencing technique developed by biologists at Texas A&M University

The game-changing discovery was part of a study led by Texas A&M biology doctoral candidate John C. Aldrich and Dr. Keith A. Maggert, an associate professor in the Department of Biology, to measure variation in heterochromatin. This mysterious, tightly packed section of the vast, non-coding section of the human genome, widely dismissed by geneticists as "junk," previously was thought by scientists to have no discernable function at all.

In the course of his otherwise routine analysis of DNA in fruit flies, Aldrich was able to monitor dynamics of the heterochromatic sequence by modifying a technique called quantitative polymerase chain reaction (QPCR), a process used to amplify specific DNA sequences from a relatively small amount of starting material. He then added a fluorescent dye, allowing him to monitor the fruit-fly DNA changes and to observe any variations.

Aldrich's findings, published today in the online edition of the journal PLOS ONE, showed that differences in the heterochromatin exist, confirming that the junk DNA is not stagnant as researchers originally had believed and that mutations which could affect other parts of the genome are capable of occurring.

"We know that there is hidden variation there, like disease proclivities or things that are evolutionarily important, but we never knew how to study it," Maggert said. "We couldn't even do the simplest things because we didn't know if there was a little DNA or a lot of it.

"This work opens up the other non-coding half of the genome."

Maggert explains that chromosomes are located in the nuclei of all human cells, and the DNA material in these chromosomes is made up of coding and non-coding regions. The coding regions, known as genes, contain the information necessary for a cell to make proteins, but far less is known about the non-coding regions, beyond the fact that they are not directly related to making proteins.

"Believe it or not, people still get into arguments over the definition of a gene," Maggert said. "In my opinion, there are about 30,000 protein-coding genes. The rest of the DNA -- greater than 90 percent -- either controls those genes and therefore is technically part of them, or is within this mush that we study and, thanks to John, can now measure. The heterochromatin that we study definitely has effects, but it's not possible to think of it as discrete genes. So, we prefer to think of it as 30,000 protein-coding genes plus this one big, complex one that can orchestrate the other 30,000."

Although other methods of measuring DNA are technically available, Aldrich notes that, as of yet, none has proven to be as cost-effective nor time-efficient as his modified-QPCR-fluorescence technique.

"There's some sequencing technology that can also be used to do this, but it costs tens of thousands of dollars," Aldrich said. "This enables us to answer a very specific question right here in the lab."

The uncharted genome sequences have been a point of contention in scientific circles for more than a decade, according to Maggert, a Texas A&M faculty member since 2004. It had long been believed that the human genome -- the blueprint for humanity, individually and as a whole -- would be packed with complex genes with the potential to answer some of the most pressing questions in medical biology.

When human DNA was finally sequenced with the completion of the Human Genome Project in 2003, he says that perception changed. Based on those initial reports, researchers determined that only two percent of the genome (about 21,000 genes) represented coding DNA. Since then, numerous other studies have emerged debating the functionality, or lack thereof, of non-coding, so-called "junk DNA."

Now, thanks to Aldrich's and Maggert's investigation of heterochromatin, the groundwork has been laid to study the rest of the genome. Once all of it is understood, scientists may finally find the root causes and possibly treatments for many genetic ailments.

"There is so much talk about understanding the connection between genetics and disease and finding personalized therapies," Maggert said. "However, this topic is incomplete unless biologists can look at the entire genome. We still can't -- yet -- but at least now, we're a step closer."

PARTICULAR BRAIN CONNECTIONS LINKED TO POSITIVE HUMAN TRAITS

There is a strong correspondence between a particular set of connections in the brain and positive lifestyle and behaviour traits, according to a new study by Oxford University researchers.

A team of scientists led by the University's Centre for Functional MRI of the Brain has investigated the connections in the brains of 461 people and compared them with 280 different behavioural and demographic measures that were recorded for the same participants. They found that variation in brain connectivity and an individual's traits lay on a single axis -- where those with classically positive lifestyles and behaviours had different connections to those with classically negative ones. The findings are published in Nature Neuroscience.

The team used data from the Human Connectome Project (HCP), a $30m NIH-funded brain imaging study led by Washington, Minnesota and Oxford Universities. The HCP is pairing up functional MRI scans of 1,200 healthy participants with in-depth data gained from tests and questionnaires. "The quality of the imaging data is really unprecedented," explains Professor Stephen Smith, who was the lead author of the paper. "Not only is the number of subjects we get to study large, but the spatial and temporal resolution of the fMRI data is way ahead of previous large datasets." So far, data for 500 subjects have been released to researchers for analysis.

The Oxford team took the data from 461 of the scans and used it to create an averaged map of the brain's processes across the participants. "You can think of it as a population-average map of 200 regions across the brain that are functionally distinct from each other," explains Professor Smith. "Then, we looked at how much all of those regions communicated with each other, in every participant."

The result is a connectome for every subject: a detailed description of how much those 200 separate brain regions communicate with each other, which can be thought of as a map of the brain's strongest connections. The team then added the 280 different behavioural and demographic measures for each subject and performed a 'canonical correlation analysis' between the two data sets -- a mathematical process that can unearth relationships between the two large sets of complex variables.

They found one strong correlation that relates specific variations in a subject's connectome with their behavioural and demographic measures. Interestingly, the correlation shows that those with a connectome at one end of scale score highly on measures typically deemed to be positive, such as vocabulary, memory, life satisfaction, income and years of education. Meanwhile, those at the other end of the scale were found to exhibit high scores for traits typically considered negative, such as anger, rule-breaking, substance use and poor sleep quality.

The researchers point out that their results resemble what psychologists refer to as the 'general intelligence g-factor': a variable first proposed in 1904 that's sometimes used to summarize a person's abilities at different cognitive tasks. While the new results include many real-life measures not included in the g-factor -- such as income and life satisfaction, for instance -- those such as memory, pattern recognition and reading ability are strongly mirrored.

Proponents of the g-factor point out that many intelligence-related measures are inter-related -- suggesting that if you're good at one thing, you're likely to be good at the others, too. However, in the past, the g-factor has also received some criticism, partly because it is not necessarily clear if these correlations between different cognitive abilities are truly reflecting correlations between distinct underlying brain circuits. The new results, however, may provide an opportunity to understand if that's correct, or if the processes in the brain tell a more complex story.

"It may be that with hundreds of different brain circuits, the tests that are used to measure cognitive ability actually make use of different sets of overlapping circuits," explains Professor Smith. "We hope that by looking at brain imaging data we'll be able to relate connections in the brain to the specific measures, and work out what these kinds of test actually require the brain to do."

The team will continue to pursue this investigation as the set of Human Connectome Project data sets made available to researchers increases.

UNDERSTANDING PARALLELS OF HUMAN AND ANIMAL PARENTING CAN BENEFIT GENERATIONS TO COME

Strong evidence now shows that human and animal parenting share many nervous system mechanisms. This is the conclusion of Yerkes National Primate Research Center researchers Larry Young, PhD, and James Rilling, PhD, in their review article about the biology of mammalian parenting, published in this week's issue of Science. Better understanding this biology could lead to improved social development, benefitting generations of humans and animals to come.

In their article, Young and Rilling review the biological mechanisms governing a shift in mammals' parental motivation that begins with aversion and transforms into irresistible attraction after giving birth. They say the same molecules that prepare the uterus for pregnancy, stimulate milk production and initiate labor also activate specific neural pathways to motivate parents to nurture, bond with and protect their offspring.

According to Young, "We have learned a tremendous amount about the specific hormonal and brain mechanisms regulating parental behavior and how parental nurturing influences the development of the offspring brain by using animal models, and many of these same mechanisms influence human parenting behavior as well."

Young is division chief of Behavioral Neuroscience and Psychiatric Disorders at the Yerkes Research Center, director of the Center for Translational Social Neuroscience at Emory, a William P. Timmie professor in the Department of Psychiatry at Emory's School of Medicine and author of The Chemistry Between Us: Love, Sex and the Science of Attraction, which also summarizes the parallels between brain mechanisms regulating sexual and parenting behaviors in animals and humans.

Rilling, who is a Yerkes researcher and an associate professor in Emory's Department of Anthropology, adds, "The human brain has mechanisms in place to support parent-child bonding, and when functioning properly, these mechanisms facilitate the development of secure attachment and sound mental health that is transmitted across generations."

The researchers divided their review into nine categories, including neural correlates of human parental care, two specific to parenting and oxytocin, two focused specifically on paternal caregiving by fathers and two related to the effect of parenting on social development. Examples within these categories include that the frustration inconsolable infant crying induces is a risk factor for infant abuse, highlighting the importance of emotion regulation for sensitive parenting; that oxytocin affects maternal motivation and paternal behaviors essential for nurturing, bonding and defending the offspring; that testosterone may interfere with parenting effort; and that variation in parental nurturing can affect brain development, thus affecting future social behaviors.

"With this comprehensive review, we can see nervous system correlations across species that result in positive and negative parental care," says Young. "This information is critical to further studying social development in order to facilitate positive parental behaviors that will benefit generations to come," he continues.

Established in 1930, the Yerkes National Primate Research Center paved the way for what has become the National Institutes of Health-funded National Primate Research Center (NPRC) program. For more than eight decades, the Yerkes Research Center has been dedicated to conducting essential basic science and translational research to advance scientific understanding and to improve human health and well-being. Today, the Yerkes Research Center is one of only eight NPRCs. The center provides leadership, training and resources to foster scientific creativity, collaboration and discoveries, and research at the center is grounded in scientific integrity, expert knowledge, respect for colleagues, an open exchange of ideas and compassionate, quality animal care.

Within the fields of microbiology and immunology, neurologic diseases, neuropharmacology, behavioral, cognitive and developmental neuroscience, and psychiatric disorders, the center's research programs are seeking ways to: develop vaccines for infectious and noninfectious diseases; understand the basic neurobiology and genetics of social behavior and develop new treatment strategies for improving social functioning in social disorders such as autism; interpret brain activity through imaging; increase understanding of progressive illnesses such as Alzheimer's and Parkinson's diseases; unlock the secrets of memory; treat drug addiction; determine how the interaction between genetics and society shape who we are; and advance knowledge about the evolutionary links between biology and behavior.