Human Alcohol Consumption Patterns Mimicked By New Strain Of Lab Mice

Main Category: Alcohol / Addiction / Illegal Drugs
Also Included In: Genetics
Article Date: 15 Dec 2011 - 0:00 PST

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A line of laboratory mice developed by a researcher from the School of Science at Indiana University-Purdue University Indianapolis (IUPUI) drinks more alcohol than other animal models and consumes it in a fashion similar to humans: choosing alcohol over other options and binge drinking.

In previous Animal models researchers found that the animals did not get as drunk as the new strain unless alcohol was the only choice of fluids, or alcohol was administered by the experimenter. When given the option, previously bred mouse lines continued to drink water even when they ccould select alcohol.

These new mice, selectively bred over 40 generations at the School of Science at IUPUI to prefer alcohol over all other choices, will help researchers explore new aspects of the behavioral and genetic determinants of alcoholism.

In a study published online ahead of print in the journal Addiction Biology , senior author Nicholas Grahame, Ph.D., associate professor of psychology in the School of Science at IUPUI, reports on the mice he has bred since 1997. The rodents reach blood-alcohol levels of more than 260 mg/dl of alcohol daily, over three times the equivalent of the human legal driving limit and the approximate consumption level that the severest human alcoholics attain.

"The free-choice drinking demonstrated by the new mouse line provides a unique opportunity to study the excessive intake that often occurs in alcohol-dependent individuals and to explore the predisposing factors for excessive consumption, as well as the development of physiological, behavioral and toxicological outcomes following alcohol exposure," says Grahame, who is a biopsychologist specializing in alcoholism.

According to the National Institute on Alcohol Abuse and Alcoholism, part of the National Institutes of Health, an estimated 17.6 million Americans abuse alcohol or are alcohol dependent. Alcohol abuse and alcoholism can be treated but cannot be cured.

Mice share 80 percent of their genes with humans, so they are an excellent model to study alcoholism, a disease with a strong genetic component. The risk of developing alcoholism is known to be influenced by lifestyle. Animal models allow researchers to employ methods that they are unable to use in humans.

"This line of high-alcohol-seeking mice should be able to give us a better understanding of the basic brain mechanism involved in alcohol consumption as well as greater insight into the toxic effects on the brain, with the goal of developing therapies," said Grahame, whose research focuses on behavioral genetics and behavioral pharmacology.

As with humans, the mice become intoxicated when the pace of alcohol consumption is faster than the liver can eliminate it. Typically it takes six or seven hours of continuous alcohol drinking for the new breed of mice to reach the highest levels of intoxication.

Doctoral candidate Liana M. Matson is a co-author of the study. She has conducted research focusing on when the mice drink and determined that they are nocturnal drinkers. This knowledge enabled the mice's blood-alcohol levels to be tested when at their highest level.

Undergraduate School of Science students Amy Buckingham and Nick Villalta assisted in the research by measuring intake and blood-alcohol levels in the new strain of high-alcohol-seeking mice. In a related study, they analyzed how drunk the mice became by testing how they performed on a balance beam.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our alcohol / addiction / illegal drugs section for the latest news on this subject. Development of the mouse line and the Addiction Biology study were funded by NIAAA and the School of Science at IUPUI.
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Swarms Of Bees Could Unlock Secrets To Human Brains

Main Category: Neurology / Neuroscience
Article Date: 13 Dec 2011 - 0:00 PST

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Scientists at the University of Sheffield believe decision making mechanisms in the human brain could mirror how swarms of bees choose new nest sites.

Striking similarities have been found in decision making systems between humans and insects in the past but now researchers believe that bees could teach us about how our brains work.

Experts say the insects even appear to have solved indecision, an often paralysing thought process in humans, with scouts who seek out any honeybees advertising rival nest sites and butt against them with their heads while producing shrill beeping sounds.

Dr James Marshall, of the University of Sheffield's Department of Computer Science, who led the UK involvement in the project and has also previously worked on similarities between how brains and insect colonies make decisions, said: "Up to now we've been asking if honeybee colonies might work in the same way as brains; now the new mathematical modelling we've done makes me think we should be asking whether our brains might work like honeybee colonies.

"Many people know about the waggle dance that honeybees use to direct hive mates to rich flower patches and new nest sites. Our research published in the journal Science (on December 9), shows that this isn't the only way that honeybees communicate with each other when they are choosing a new nest site; they also disrupt the waggle dances of bees that are advertising alternative sites."

Biologists from Cornell University, New York, University of California Riverside and the University of Bristol set up two nest boxes for a homeless honeybee swarm to choose between and recorded how bees that visited each box interacted with bees from the rival box. They found that bees that visited one site, which were marked with pink paint, tended to inhibit the dances of bees advertising the other site, which were marked with yellow paint, and vice versa

Tom Seeley of Cornell University, author of the best-selling book Honeybee Democracy said "We were amazed to discover that the bees from one nest box would seek out bees performing waggle dances for the other nest box and butt against them with their heads while simultaneously producing shrill beeping sounds. We call this rough treatment the 'stop signal' because most bees that receive this signal will cease dancing a few seconds later."

Dr Patrick Hogan of the University of Sheffield, who constructed the mathematical model of the bees, added: "The bees target their stop signal only at rivals within the colony, preventing the colony as a whole from becoming deadlocked with indecision when choosing a new home. This remarkable behaviour emerges naturally from the very simple interactions observed between the individual bees in the colony."

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Decision Making In Bee Swarms Mimic Neurons In Human Brains

Main Category: Neurology / Neuroscience
Article Date: 10 Dec 2011 - 0:00 PST

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Swarms of bees and brains made up of neurons make decisions using strikingly similar mechanisms, says a new study in the Dec. 9 issue of Science.

In previous work, Cornell University biologist Thomas Seeley clarified how scout bees in a honeybee swarm perform "waggle dances" to prompt other scout bees to inspect a promising site that has been found.

In the new study, Seeley, a professor of neurobiology and behavior, reports with five colleagues in the United States and the United Kingdom that scout bees also use inhibitory "stop signals" - a short buzz delivered with a head butt to the dancer - to inhibit the waggle dances produced by scouts advertising competing sites. The strength of the inhibition produced by each group of scouts is proportional to the group's size. This inhibitory signaling helps ensure that only one of the sites is chosen. This is especially important for reaching a decision when two sites are equally good, Seeley said.

Previous research has shown that bees use stop signals to warn nest-mates about such dangers as attacks at a food source. However, this is the first study to show the use of stop signals in house-hunting decisions.

Such use of stop signals in decision making is "analogous to how the nervous system works in complex brains," said Seeley. "The brain has similar cross inhibitory signaling between neurons in decision-making circuits."

Co-authors Patrick Hogan and James Marshall of the University of Sheffield in the United Kingdom explored the implications of the bees' cross-inhibitory signaling by modeling their collective decision-making process. Their analysis showed that stop signaling helps bees to break deadlocks between two equally good sites and to avoid costly dithering.

The study was funded by the Cornell Agricultural Experiment Station, the University of California-Riverside and the U.K. Biotechnology and Biological Sciences Research Council.

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Long-Term Imaging Reveals Intriguing Patterns Of Human Brain Maturation

Main Category: Neurology / Neuroscience
Article Date: 09 Dec 2011 - 0:00 PST

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Neuroimaging has provided fascinating insight into the dynamic nature of human brain maturation. However, most studies of developmental changes in brain anatomy have considered individual locations in relative isolation from all others and have not characterized relationships between structural changes in different parts of the developing brain. Now, new research describes the first comprehensive study of coordinated anatomical maturation within the developing human brain. The study, published by Cell Press in the December 8 issue of the journal Neuron, reveals that functionally connected brain regions mature together and uncovers fascinating sex-specific differences in brain development.

"Understanding patterns of structural change in the developing human brain is a challenge because the types of change that we can detect using neuroimaging unfold rather slowly," explains lead study author, Dr. Armin Raznahan, from the National Institutes of Mental Health in Bethesda, Maryland. "So, we drew from the largest and longest-running longitudinal neuroimaging study of human brain maturation, where brain changes were tracked for over several years in the same set of individuals, to analyze patterns of correlated anatomical change across the sensitive developmental window of late childhood, adolescence, and early adulthood."

Dr. Raznahan and colleagues examined the thickness of the cortex because it can be reliably measured and its developmental changes have been described in detail. The cortex is a sheet of neural tissue that covers the surface of the brain and plays a key role in thought, language, memory and consciousness.

The researchers discovered that rates of structural maturation were highly coordinated in the cortex and that regions which were functionally connected to each other also exhibited tightly coupled patterns of maturation. Interestingly, the researchers also observed that maturational coupling within the brain regions crucial for complex decision making differed between males and females.

"Our study represents the first ever investigation of correlated anatomical maturation in the developing human brain and shows that rates of structural cortical development in different cortical regions are highly organized with respect to one another," concludes Dr. Raznahan. "By providing the first link between cortical connectivity and the coordination of cortical development, we reveal a previously unseen property of healthy brain maturation, which may represent a target for neurodevelopmental disease processes and a substrate for sexually dimorphic behavior in adolescence."

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Changes In The Path Of Brain Development Make Human Brains Unique

Main Category: Neurology / Neuroscience
Article Date: 08 Dec 2011 - 0:00 PST

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How the human brain and human cognitive abilities evolved in less than six million years has long puzzled scientists. A new study conducted by scientists in China and Germany, and published in the online, open-access journal PLoS Biology, now provides a possible explanation by showing that activity levels of genes in the human brain during development changed substantially compared to chimpanzees and macaques. What's more, these changes might be caused by a handful of key regulatory molecules called microRNAs.

The authors studied gene activity in human, chimpanzee and macaque brains across their lifetimes. Starting from newborns, they investigated two brain regions; the cerebellum, which is responsible for motor activity, and the prefrontal cortex, which has roles in more complex behavior such as social interactions or abstract thinking. They first studied the simple gene activity differences between species that are seen at all ages. Although many genes show such simple differences, there was no disparity in numbers of these differences between the human and the chimpanzee evolutionary lineages. Moreover, most of these differences were observed in both of the brain regions studied, and the genes involved are not thought to be specifically involved in brain function. In the opinion of Mehmet Somel, the lead author of the study, these differences represent evolutionary "white noise" and have little importance for human brain evolution.

The authors then looked for changes in gene activity during development, comparing the activity of genes in newborns and adults. In general, brain developmental patterns tend to be quite similar in humans, other primate species, and even mice. Nevertheless, the authors found that for hundreds of genes, humans display unique developmental patterns, with profiles that were different in shape and/or timing from those found in chimpanzees and macaques. Such human-specific developmental gene activity patterns were particularly widespread in the prefrontal cortex, where genes showing human-specific changes outnumbered genes showing chimpanzee-specific changes by four-fold. Developmental patterns in the cerebellum, by contrast, were much less human-specific. Furthermore, many genes displaying these human-specific patterns in the prefrontal cortex were known to have specific neural functions, implying roles in human cognitive development.

Looking for possible causes of this widespread developmental remodeling in the human prefrontal cortex, the authors stumbled upon an unexpected signal. Developmental patterns of genes that encode microRNAs (tiny but powerful regulators that target many other genes and processes) showed even greater excess of human-specific changes in the prefrontal cortex than did comparable developmental patterns in ordinary genes. Several of these changes in microRNA activity could be directly linked to human-specific changes in activity of their target genes. Since each microRNA may regulate the activity of hundreds of other genes, this finding provides a possible explanation to how hundreds of genes changed their activity patterns (in a coordinated way) during human brain development.

This result further implies that the evolution of human cognitive abilities might be traced back to a small number of mutations in key developmental regulators. Philipp Khaitovich, the senior author of the study, suggests that "identifying the exact genetic changes that made us think and act like humans might be easier than we previously imagined". This said, it is likely to require much more work with a focus on the dynamics of brain development and wider use of transgenic mice, and even primate models.

Further to this, the authors point out that identification of the key human-specific DNA mutations could help us to determine how close the Neanderthals' cognitive abilities were to ours. "If Neanderthals' brain development was similar to that of chimpanzees and macaques, it would be no wonder that they became extinct when confronted by Modern Humans," says Mehmet Somel.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our neurology / neuroscience section for the latest news on this subject. Funding: The study was funded by the Ministry of Science and Technology of the People's Republic of China (grant no. 2007CB947004), Chinese Academy of Sciences (grant no. KSCX2-YW-R-094 and KSCX2-YW-R-251), the Shanghai Institutes for Biological Sciences (grant no. 2008KIT104), National Science Foundation of China research grant (grant no. 31010022 & 31050110128), the Max Planck-Society, and the Bundesministerum fuer Bildung und Forschung. MS was supported by fellowships from the Chinese Academy of Sciences (2009Y2BS12) and European Molecular Biology Organization (EMBO ALTF 1475-2010). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Citation: Somel M, Liu X, Tang L, Yan Z, Hu H, et al. (2011) MicroRNA-Driven Developmental Remodeling in the Brain Distinguishes Humans from Other Primates. PLoS Biol 9(12): e1001214. doi:10.1371/journal.pbio.1001214
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