Being in Awe Can Expand Time and Enhance Well-Being

ScienceDaily (July 19, 2012) — It doesn’t matter what we’ve experienced — whether it’s the breathtaking scope of the Grand Canyon, the ethereal beauty of the Aurora Borealis, or the exhilarating view from the top of the Eiffel Tower — at some point in our lives we’ve all had the feeling of being in a complete and overwhelming sense of awe.


Awe seems to be a universal emotion, but it has been largely neglected by scientists — until now.

Psychological scientists Melanie Rudd and Jennifer Aaker of Stanford University Graduate School of Business and Kathleen Vohs of the University of Minnesota Carlson School of Management devised a way to study this feeling of awe in the laboratory. Across three different experiments, they found that jaw-dropping moments made participants feel like they had more time available and made them more patient, less materialistic, and more willing to volunteer time to help others.

The researchers found that the effects that awe has on decision-making and well-being can be explained by awe’s ability to actually change our subjective experience of time by slowing it down. Experiences of awe help to brings us into the present moment which, in turn, adjusts our perception of time, influences our decisions, and makes life feel more satisfying than it would otherwise.

Now that’s awesome.

 

Link:

http://www.psychologicalscience.org/index.php/news/releases/being-in-awe-can-expand-time-and-enhance-well-being.html

Journal Reference:

  1. Melanie Rudd, Jennifer Aaker and Kathleen Vohs. Awe Expands People’s Perception of Time, Alters Decision Making, and Enhances Well-Being. Psychological Science, 2012

Citation:

Association for Psychological Science (2012, July 19). Being in awe can expand time and enhance well-being. ScienceDaily. Retrieved July 21, 2012, from http://www.sciencedaily.com­ /releases/2012/07/120719161901.htm

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What 10,000 Fruit Flies Have to Tell Us About Differences Between the Sexes

ScienceDaily (July 19, 2012) — What do you get when you dissect 10 000 fruit-fly larvae? A team of researchers led by the EMBL-European Bioinformatics Institute (EMBL-EBI) in the UK and the Max Planck Institute of Immunobiology and Epigenetics (MPI) in Freiburg, Germany has discovered a way in which cells can adjust the activity of many different genes at once. Their findings, published in the journal Science, overturn commonly held views and reveal an important mechanism behind sex differences.


Asifa Akhtar’s laboratory, previously at EMBL now at MPI, studies precisely how flies regulate an important set of genes. Females have two X chromosomes while males have only one, so the genes on the female X chromosomes somehow need to be kept from producing twice as many proteins as those on the male X chromosome. Male fruit flies get around this by making their X chromosome’s genes work double time: an epigenetic enzyme doubles the output of thousands of different genes. But just how much that doubled output is can vary tremendously from one gene to the next.

“Imagine that you have thousands of half-filled glasses of all different sizes and shapes,” explains Nick Luscombe, who led the work at EMBL-EBI. “Now imagine that you have to fill them all up to the top at the same time. This is an incredibly complex mechanism.”

To see how genes are expressed, scientists try to pinpoint signals that show when a gene increases its output. In most studies of this kind, this output is increased by a factor of between 10 and 100 when a gene is being expressed. In this study, the signal involved is miniscule: an increase of only a factor of two.

Observing such a faint signal is a major challenge. But thanks to the painstaking fly-larvae dissection efforts of graduate student Thomas Conrad, combined with the detailed analytical efforts of Florence Cavalli and Juanma Vaquerizas, the team gathered enough material to measure this output and compare males and females directly.

The scientists found twice as many DNA-transcribing (reading) proteins — known as polymerases — attached to the male X chromosome as to the female version. This means that the difference between males and females is rooted in the beginning of the transcription process, when the polymerase first binds to the DNA. This goes against the commonly held view that the regulation mechanism is kicked off during transcription.

“A factor of two appears miniscule, so it is not easy to measure accurately,” says Akhtar. “We were really doing a bulk analysis of several hundred genes, and that required a lot of careful bioinformatics analysis. Our group would run experiments, Nick’s would analyse the data, and then we would decide on new experiments together to be sure that what we were seeing was real.”

Discovering the machinery that doubles the expression of male X-chromosome genes could well have implications that go far beyond the humble fly. Speaking more technically, Luscombe says: “This is the first direct, clear mechanism that links a histone modification and the activity of a polymerase across thousands of genes.”

Looking into future directions, Akhtar says: “We now need to look more deeply into what makes this kind of mass regulation possible, and how it fits in with other means cells may have to fine-tune their use of genetic information.”

Link:

http://www.ebi.ac.uk/Information/News/press-releases/press-release-20072012-Luscombe_Science.html

Journal Reference:

  1. Conrad, T., Cavalli, F.M.G., Vaquerizas, J.M., Luscombe, N.M., Akhtar, A. Drosophila dosage compensation involves enhanced Pol II recruitment to male X-linked promoters. Science, 2012 DOI: 10.1126/science.1221428

Citation:

European Molecular Biology Laboratory – European Bioinformatics Institute (2012, July 19). What 10,000 fruit flies have to tell us about differences between the sexes. ScienceDaily. Retrieved July 21, 2012, from http://www.sciencedaily.com­ /releases/2012/07/120719141806.htm

Scientists Read Monkeys’ Inner Thoughts: Brain Activity Decoded While Monkeys Avoid Obstacle to Touch Target

ScienceDaily (July 19, 2012) — By decoding brain activity, scientists were able to “see” that two monkeys were planning to approach the same reaching task differently — even before they moved a muscle.


Anyone who has looked at the jagged recording of the electrical activity of a single neuron in the brain must have wondered how any useful information could be extracted from such a frazzled signal.

But over the past 30 years, researchers have discovered that clear information can be obtained by decoding the activity of large populations of neurons.

Now, scientists at Washington University in St. Louis, who were decoding brain activity while monkeys reached around an obstacle to touch a target, have come up with two remarkable results.

Their first result was one they had designed their experiment to achieve: they demonstrated that multiple parameters can be embedded in the firing rate of a single neuron and that certain types of parameters are encoded only if they are needed to solve the task at hand.

Their second result, however, was a complete surprise. They discovered that the population vectors could reveal different planning strategies, allowing the scientists, in effect, to read the monkeys’ minds.

By chance, the two monkeys chosen for the study had completely different cognitive styles. One, the scientists said, was a hyperactive type, who kept jumping the gun, and the other was a smooth operator, who waited for the entire setup to be revealed before planning his next move. The difference is clearly visible in their decoded brain activity.

The study was published in the July 19th advance online edition of the journal Science.

All in the task

The standard task for studying voluntary motor control is the “center-out task,” in which a monkey or other subject must move its hand from a central location to targets placed on a circle surrounding the starting position.

To plan the movement, says Daniel Moran, PhD, associate professor of biomedical engineering in the School of Engineering & Applied Science and of neurobiology in the School of Medicine at Washington University in St. Louis, the monkey needs three pieces of information: current hand and target position and the velocity vector that the hand will follow.

In other words, the monkey needs to know where his hand is, what direction it is headed and where he eventually wants it to go.

A variation of the center-out task with multiple starting positions allows the neural coding for position to be separated from the neural coding for velocity.

By themselves, however, the straight-path, unimpeded reaches in this task don’t let the neural coding for velocity to be distinguished from the neural coding for target position, because these two parameters are always correlated. The initial velocity of the hand and the target are always in the same direction.

To solve this problem and isolate target position from movement direction, doctoral student Thomas Pearce designed a novel obstacle-avoidance task to be done in addition to the center-out task.

Crucially, in one-third of the obstacle-avoidance trials, either no obstacle appeared or the obstacle didn’t block the monkey’s path. In either case, the monkey could move directly to the target once he got the “go” cue.

The population vector corresponding to target position showed up during the third hold of the novel task, but only if there was an obstacle. If an obstacle appeared and the monkey had to move its hand in a curved trajectory to reach the target, the population vector lengthened and pointed at the target. If no obstacle appeared and the monkey could move directly to the target, the population vector was insignificant.

In other words, the monkeys were encoding the position of the target only when it did not lie along a direct path from the starting position and they had to keep its position “in mind” as they initially moved in the “wrong” direction.

“It’s all,” Moran says, “in the design of the task.”

And then some magic happens

Pearce’s initial approach to analyzing the data from the experiment was the standard one of combining the data from the two monkeys to get a cleaner picture.

“It wasn’t working,” Pearce says, “and I was frustrated because I couldn’t figure out why the data looked so inconsistent. So I separated the data by monkey, and then I could see, wow, they’re very different. They’re approaching this task differently and that’s kind of cool.”

The difference between the monkey’s’ styles showed up during the second hold. At this point in the task, the target was visible, but the obstacle had not yet appeared.

The hyperactive monkey, called monkey H, couldn’t wait. His population vector during that hold showed that he was poised for a direct reach to the target. When the obstacle was then revealed, the population vector shortened and rotated to the direction he would need to move to avoid the obstacle.

The smooth operator, monkey G, in the meantime, idled through the second hold, waiting patiently for the obstacle to appear. Only when it was revealed did he begin to plan the direction he would move to avoid the obstacle.

Because he didn’t have to correct course, monkey G’s strategy was faster, so what advantage was it to monkey H to jump the gun? In the minority of trials where no obstacle appeared, monkey H approached the target more accurately than monkey G. Maybe monkey H is just cognitively adapted to a Whac-A-Mole world. And monkey G, when caught without a plan, was at a disadvantage.

Working with the monkeys, the scientists had been aware that they had very different personalities, but they had no idea this difference would show up in their neural recordings.

“That’s what makes this really interesting,” Moran says.

Link:

https://news.wustl.edu/news/Pages/24043.aspx

Journal Reference:

  1. Thomas M. Pearce and    Daniel W. Moran. Strategy-Dependent Encoding of Planned Arm Movements in the Dorsal Premotor Cortex. Science, 2012; DOI: 10.1126/science.1220642

Citation:

Washington University in St. Louis (2012, July 19). Scientists read monkeys’ inner thoughts: Brain activity decoded while monkeys avoid obstacle to touch target. ScienceDaily. Retrieved July 21, 2012, from http://www.sciencedaily.com­ /releases/2012/07/120719141804.htm

Entire Genetic Sequence of Individual Human Sperm Determined

ScienceDaily (July 19, 2012) — The entire genomes of 91 human sperm from one man have been sequenced by Stanford University researchers. The results provide a fascinating glimpse into naturally occurring genetic variation in one individual, and are the first to report the whole-genome sequence of a human gamete — the only cells that become a child and through which parents pass on physical traits.


“This represents the culmination of nearly a decade of work in my lab,” said Stephen Quake, PhD, the Lee Otterson Professor in the School of Engineering and professor of bioengineering and of applied physics. “We now have devices that will allow us to routinely amplify and sequence to a high degree of accuracy the entire genomes of single cells, which has far-ranging implications for the study of cancer, infertility and many other disorders.”

Quake is the senior author of the research, published July 20 in Cell. Graduate student Jianbin Wang and former graduate student H. Christina Fan, PhD, now a senior scientist at ImmuMetrix, share first authorship of the paper.

Sequencing sperm cells is particularly interesting because of a natural process called recombination that ensures that a baby is a blend of DNA from all four of his or her grandparents. Until now, scientists had to rely on genetic studies of populations to estimate how frequently recombination had occurred in individual sperm and egg cells, and how much genetic mixing that entailed.

“Single-sperm sequencing will allow us to chart and understand how recombination differs between individuals at the finest scales. This is an important proof of principle that will allow us to study both fundamental dynamics of recombination in humans and whether it is involved in issues relating to male infertility,” said Gilean McVean, PhD, professor of statistical genetics at the Wellcome Trust Centre for Human Genetics. McVean was not involved in the research.

The Stanford study showed that the previous, population-based estimates were, for the most part, surprisingly accurate: on average, the sperm in the sample had each undergone about 23 recombinations, or mixing events. However, individual sperm varied greatly in the degree of genetic mixing and in the number and severity of spontaneously arising genetic mutations. Two sperm were missing entire chromosomes. The study has long-ranging implication for infertility doctors and researchers.

“For the first time, we were able to generate an individual recombination map and mutation rate for each of several sperm from one person,” said study co-author Barry Behr, PhD, HCLD, professor of obstetrics and gynecology and director of Stanford’s in vitro fertilization laboratory. “Now we can look at a particular individual, make some calls about what they would likely contribute genetically to an embryo and perhaps even diagnose or detect potential problems.”

Most cells in the human body have two copies of each of 23 chromosomes, and are known as “diploid” cells. Recombination occurs during a process called meiosis, which partitions a single copy of each chromosome into a sperm (in a man) or egg (in a woman) cell. When a sperm and an egg join, the resulting fertilized egg again has a full complement of DNA.

To ensure an orderly distribution during recombination, pairs of chromosomes are lined up in tight formation along the midsection of the cell. During this snug embrace, portions of matching chromosomes are sometimes randomly swapped. The process generates much more genetic variation in a potential offspring than would be possible if only intact chromosomes were segregated into the reproductive cells.

“The exact sites, frequency and degree of this genetic mixing process is unique for each sperm and egg cell,” said Quake, “and we’ve never before been able to see it with this level of detail. It’s very interesting that what happens in one person’s body mirrors the population average.”

Major problems with the recombination process can generate sperm missing portions or even whole chromosomes, making them incapable of or unlikely to fertilize an egg. But it can be difficult for fertility researchers to identify potential problems.

“Most of the techniques we currently use to assess sperm viability are fairly crude,” said Quake.

To conduct the research, Wang, Quake and Behr first isolated and sequenced nearly 100 sperm cells from the study subject, a 40-year-old man. The man has healthy offspring, and the semen sample appeared normal. His whole-genome sequence (obtained from diploid cells) has been previously sequenced to a high level of accuracy.

They then compared the sequence of the sperm with that of the study subject’s diploid genome. They could see, by comparing the sequences of the chromosomes in the diploid cells with those in the haploid sperm cells, where each recombination event took place. The researchers also identified 25 to 36 new single nucleotide mutations in each sperm cell that were not present in the subject’s diploid genome. Such random mutations are another way to generate genetic variation, but if they occur at particular points in the genome they can have deleterious effects.

It’s important to note that individual sperm cells are destroyed by the sequencing process, meaning that they couldn’t go on to be used for fertilization. However, the single-cell sequencing described in the paper could potentially be used to diagnose male reproductive disorders and help infertile couples assess their options. It could also be used to learn more about how male fertility and sperm quality change with increasing age.

“This could serve as a new kind of early detection system for men who may have reproductive problems,” said Behr, who also co-directs Stanford’s reproductive endocrinology and infertility program. “It’s also possible that we could one day use other, correlating features to harmlessly identify healthy sperm for use in IVF. In the end, the DNA is the raw material that ultimately defines a sperm’s potential. If we can learn more about this process, we can better understand human fertility.”

The research was supported by the National Institute of Health, the Chinese Scholarship Council and the Siebel Foundation.

 

Link:

http://med.stanford.edu/ism/2012/july/sperm.html

Journal Reference:

  1. Jianbin Wang, H. Christina Fan, Barry Behr, Stephen R. Quake. Genome-wide Single-Cell Analysis of Recombination Activity and De Novo Mutation Rates in Human Sperm. Cell, 20 July 2012 DOI: 10.1016/j.cell.2012.06.030

Citation:

Stanford University Medical Center (2012, July 19). Entire genetic sequence of individual human sperm determined. ScienceDaily. Retrieved July 21, 2012, from http://www.sciencedaily.com­

 

Does Presence of Oxidants Early in Life Help Determine Life Span?

ScienceDaily (July 19, 2012) — Why do we age, and what makes some of us live longer than others? For decades, researchers have been trying to answer these questions by elucidating the molecular causes of aging.


One of the most popular theories is that the accumulation of oxygen radicals over time might be the underlying culprit in aging. Oxygen radicals are chemically reactive molecules that can damage cellular components such as lipids, proteins and nucleic acids, resulting in “oxidative stress.”

The possible link between oxidative stress and aging has led to the proliferation of antioxidant products ranging from dietary supplements to anti-aging creams. However, the role of oxidative stress in aging is still controversial, and the effectiveness of these antioxidants is debatable.

In a paper to be published online July 19 in the journal Molecular Cell, University of Michigan molecular biologist Ursula Jakob and her co-workers measured reactive oxygen species in worms and identified the processes affected by oxidative stress.

Using the small roundworm C. elegans, a popular model organism for aging studies, they made several surprising observations. They found that these animals are forced to deal with very high levels of reactive oxygen species long before old age. High levels of reactive oxygen were found to accumulate during early development (i.e., the childhood of the worm).

Once these worms reached adulthood the levels of reactive oxygen declined, only to surge again later in life. Intriguingly, mutant worm variants that were destined to live a very long time were able to cope much better with reactive oxygen and recovered earlier than short-lived variants.

This finding suggests that the ability to deal with and recover from early oxidative stress might be a harbinger of the lifespan of the animals, according to the U-M researchers.

“We fully expected to see increased levels of reactive oxygen species in older animals, but the observation that very young animals transiently produce these very high levels of oxidants came truly as a big surprise,” said Daniela Knoefler, a doctoral candidate in Jakob’s lab and one of the lead authors of the study.

“Of course, we have no idea whether this is also the case in humans,” said Jakob, a professor in the Department of Molecular, Cellular and Developmental Biology in the College of Literature, Science, and the Arts and a professor in the Department of Biological Chemistry at the Medical School.

“However, there are some convincing studies conducted in mice which show that manipulating metabolism in the first few weeks of life can produce a substantial slowing of the aging process and increase in life span,” Jakob said.

Now, the search is on to discover the mechanism behind this early oxidant accumulation and the fascinating possibility that by manipulating these levels of reactive oxygen early in life, researchers could potentially affect the lifespan of the organisms, Jakob said.

In addition to Knoefler and Jakob, authors of the Molecular Cell paper are Maike Thamsen, Martin Koniczek, Nicholas Niemuth and Ann-Kristen Diederich, all of U-M.

The work was supported by the National Institute of Aging, an Office of the Vice President for Research grant from U-M, the National Center for Research Resources and the National Institutes of Health.

 

Link:

http://ns.umich.edu/new/releases/20640-does-presence-of-oxidants-early-in-life-help-determine-life-span

Citation:

University of Michigan (2012, July 19). Does presence of oxidants early in life help determine life span?. ScienceDaily. Retrieved July 21, 2012, from http://www.sciencedaily.com­ /releases/2012/07/120719132559.htm

How Does Fat Influence Flavor Perception?

ScienceDaily (July 19, 2012) — A joint study carried out by The University of Nottingham and the multinational food company Unilever has found for the first time that fat in food can reduce activity in several areas of the brain which are responsible for processing taste, aroma and reward.


The research, now available in the Springer journal Chemosensory Perception, provides the food industry with better understanding of how in the future it might be able to make healthier, less fatty food products without negatively affecting their overall taste and enjoyment. Unveiled in 2010, Unilever’s Sustainable Living Plan sets out its ambition to help hundreds of millions of people improve their diet around the world within a decade.

This fascinating three-year study investigated how the brains of a group of participants in their 20s would respond to changes in the fat content of four different fruit emulsions they tasted while under an MRI scanner. All four samples were of the same thickness and sweetness, but one contained flavour with no fat, while the other three contained fat with different flavour release properties.

The research found that the areas of the participants’ brains which are responsible for the perception of flavour — such as the somatosensory cortices and the anterior, mid & posterior insula — were significantly more activated when the non-fatty sample was tested compared to the fatty emulsions despite having the same flavour perception. It is important to note that increased activation in these brain areas does not necessarily result in increased perception of flavour or reward.

Dr Joanne Hort, Associate Professor in Sensory Science at The University of Nottingham said: “This is the first brain study to assess the effect of fat on the processing of flavour perception and it raises questions as to why fat emulsions suppress the cortical response in brain areas linked to the processing of flavour and reward. It also remains to be determined what the implications of this suppressive effect are on feelings of hunger, satiety and reward.”

Unilever food scientist Johanneke Busch, based at the company’s Research & Development laboratories in Vlaardingen, Netherlands added: “There is more to people’s enjoyment of food than the product’s flavour — like its mouthfeel, its texture and whether it satisfies hunger, so this is a very important building block for us to better understand how to innovate and manufacture healthier food products which people want to buy.”

Nottingham University’s Sensory Science Centre, its Sir Peter Mansfield Magnetic Resonance Centre and the Nottingham Digestive Diseases Centre were all involved in the research.

The study was co-funded by the Biotechnology and Biological Sciences Research Council.

 

Link:

http://www.nottingham.ac.uk/news/pressreleases/2012/july/new-research-questions-how-fat-influences-flavour-perception.aspx

Journal Reference:

  1. Sally Eldeghaidy, Tracey Hollowood, Luca Marciani, Kay Head, Johanneke Busch, Andrew J. Taylor, Tim J. Foster, Robin C. Spiller, Penny A. Gowland, Sue Francis, Joanne Hort. Does Fat Alter the Cortical Response to Flavor? Chemosensory Perception, 2012; DOI: 10.1007/s12078-012-9130-z

Retreived:

University of Nottingham (2012, July 19). How does fat influence flavor perception?. ScienceDaily. Retrieved July 21, 2012, from http://www.sciencedaily.com­ /releases/2012/07/120719105034.htm

Skin Has an Internal Clock

ScienceDaily (July 19, 2012) — A research team at Charité – Universitätsmedizin Berlin together with scientists at a company in Hamburg has now discovered that human skin has an internal clock responsible for the time-based steering of its repair and regeneration, among other things.


 

The team published its first results from their basic research in the current issue of Proceedings of the National Academy of Sciences (PNAS).
Our skin is one of the body’s essential organs and perhaps the most versatile: Besides representative, communicative and sensory functions, it serves as our body’s boundary to the environment, forms an active and passive barrier against germs and helps keeping conditions constant for other important systems of the body, even though environmental conditions can change drastically. Frost, heat, sunlight and moisture — a variety of challenges for our skin — have different effects depending on the time of day.
Prof. Achim Kramer’s research team from the field of chronological biology at Charité and Dr. Thomas Blatt from the Skin Research Center in Hamburg have now found out that skin adapts to these time-dependent conditions.
The researchers took cell samples (keratinocytes) from the uppermost layer of skin from young, healthy test persons at various times of the day. Analysis of numerous genes in the keratinocytes showed that important factors for the regeneration and repair of skin cells are regulated by a biological clock. One of these factors, the molecule called the Krüppel-like-factor (Klf9) slows down cell division in the keratinocytes: When the researchers reduced the activity of this factor, they observed faster growth in the skin cell cultures. On the other hand, increased activity of Klf9 was connected with slower cell division. At the same time, it was shown that the stress hormone cortisol also controls the activity of Klf9 and can thus deploy a medical effect on common skin diseases like psoriasis.
The job of the biological clock is to control the exact timing of various processes like cell division, cell differentiation and DNA repair in skin. Prof. Kramer is already looking to the future: “If we understand these processes better, we could target the use of medication to the time of day in which they work best and have the fewest side effects.”

 

Journal Reference:

  1. F. Sporl, S. Korge, K. Jurchott, M. Wunderskirchner, K. Schellenberg, S. Heins, A. Specht, C. Stoll, R. Klemz, B. Maier, H. Wenck, A. Schrader, D. Kunz, T. Blatt, A. Kramer. Kruppel-like factor 9 is a circadian transcription factor in human epidermis that controls proliferation of keratinocytes. Proceedings of the National Academy of Sciences, 2012; 109 (27): 10903 DOI: 10.1073/pnas.1118641109

 

Charité – Universitätsmedizin Berlin (2012, July 19). Skin has an internal clock. ScienceDaily. Retrieved July 21, 2012, from http://www.sciencedaily.com­ /releases/2012/07/120719103608.htm

Spatial Knowledge Vs. Spatial Choice: The Hippocampus as Conflict Detector?

ScienceDaily (July 19, 2012) — Hippocampal NMDA receptors in the brain help to make the right decision when faced with complex orientation problems.


Synapses are modified through learning. Up until now, scientists believed that a particular form of synaptic plasticity in the brain’s hippocampus was responsible for learning spatial relations. This was based on a receptor type for the neurotransmitter glutamate: the NMDA receptor. Researchers at the Max Planck Institute for Medical Research in Heidelberg and Oxford University have now observed that mice develop a spatial memory, even when the NMDA receptor-transmitted plasticity is switched off in parts of their hippocampus. However, if these mice have to resolve a conflict while getting their bearings, they are not successful in resolving it; the hippocampal NMDA receptors are clearly needed to detect or resolve the conflict. This has led the researchers involved in this experiment to refute a central tenet of neuroscience regarding the function of hippocampal NMDA receptor-transmitted plasticity in spatial learning.

The hippocampus is part of the forebrain and processes a large amount of information from various parts of the brain. Incoming signals are transmitted by granule cells in the dentate gyrus to pyramid cells in the CA3 region and from these to pyramid cells in the CA1 region. NMDA receptors can optimise or weaken the transmission efficiency of the neurotransmitter glutamate at the synapses involved at the signal flow. It has long been speculated that this form of synaptic plasticity is needed when learning about spatial associations. Rolf Sprengel and Peter H. Seeburg from the Max Planck Institute for Medical Research worked with colleagues from Oxford and Oslo to refute this theory.

The scientists studied genetically modified mice lacking NMDA receptors in dentate gyrus granule cells and pyramid cells in the CA1 region. They were thus able to observe for the first time ever what happens when NMDA receptor-dependent plasticity is switched off almost exclusively at these synapses in the hippocampus. They analysed the learning behaviour of the mice and noted that learning capacity depended on the experimental setup. In a standard swimming test (the so called Morris Water Maze), the spatial memory of the genetically modified animals was just as good as the spatial memory of the normal controls. In this test, the animals had to learn the location of an escape platform placed just under the surface of water in a pool of milky water using external cues and had to find the hidden platform after a few attempts.

In a second spatial orientation test in which the animals could find food in three of six identical arms of a “six arm dry maze,” the mice lacking NMDA receptors in the dentate gyrus and CA1 region of the hippocampus repeatedly visited arms without food, while, after a number of attempts, the controls — as in the case of the swimming test — used markings outside of the maze to enter the three arms where there was food.

Although both tests demand spatial learning, the genetically modified animals performed worse only in the maze arm than the controls, apparently irritated by the fact that arms were rewarded or not rewarded with food. David Bannerman from Oxford therefore designed a second swimming test. In this test, the location of the hidden platform was marked with a beacon. A second identical, beacon was placed at another location in the pool as a decoy — there was no platform under the water at this second location. The mice had to learn that only the spatial orientation and not the location of the beacons — like the visually identical arms in the maze — was crucial for finding the platform that would allow them to escape. As the beacons were used by the animals with a preference for hippocampus-independent orientation, it was also difficult for the controls to unerringly find the hidden platform after numerous trials. Mice lacking the NMDA receptors in the dentate gyrus and the CA1 region could not resolve this problem. If both beacons were removed or the shape of the decoy beacons was modified, all the animals quickly selected the location of the invisible platform.

“This clearly shows that, after a number of runs, even our genetically modified mice know the exact location of the hidden escape platform or can purposefully get their bearings in the swimming pool when searching for various beacons. Our mice therefore have no learning or memory problems in either of the two tasks. If, however, the tasks are temporally superimposed and if the location of identical beacons in the swimming pool does not have to be evaluated as distinct items of information, our mice are not capable of making the right decision to resolve the problem,” says Rolf Sprengel.

The NMDA receptors in the CA1 region of the hippocampus therefore seem to perform a conflict detection or decision-making role in the event of conflicts.

This is an extremely surprising result. It runs contrary to a textbook tenet that has prevailed for more than 15 years, namely that NMDA receptors in the CA1 region of the hippocampus are needed to develop spatial memory. “Thanks to Rolf Sprengel’s new complex genetic technique of switching off the NMDA receptors only in specific parts of the hippocampus in adult mice and to David Bannerman’s intelligently linked behavioural experiments, we now know that NMDA receptors in other parts of the brain are probably responsible for learning spatial relations,” explains Peter H. Seeburg. The researchers assume, therefore, that hippocampal NMDA receptors are also significant in other non-spatial conflicts.

 

Journal Reference:

  1. David M Bannerman, Thorsten Bus, Amy Taylor, David J Sanderson, Inna Schwarz, Vidar Jensen, Øivind Hvalby, J Nicholas P Rawlins, Peter H Seeburg, Rolf Sprengel. Dissecting spatial knowledge from spatial choice by hippocampal NMDA receptor deletion. Nature Neuroscience, 2012; DOI: 10.1038/nn.3166

 

Max-Planck-Gesellschaft (2012, July 19). Spatial knowledge vs. spatial choice: The hippocampus as conflict detector?. ScienceDaily. Retrieved July 21, 2012, from http://www.sciencedaily.com­ /releases/2012/07/120719103524.htm