Posts tagged memory

Posts tagged memory
Why Some Remember Dreams, Others Don’t
People who tend to remember their dreams also respond more strongly than others to hearing their name when they’re awake, new research suggests.
Everyone dreams during sleep, but not everyone recalls the mental escapade the next day, and scientists aren’t sure why some people remember more than others.
To find out, researchers used electroencephalography to record the electrical activity in the brains of 36 people while the participants listened to background tunes, and occasionally heard their own first name. The brain measurements were taken during wakefulness and sleep. Half of the participants were called high recallers, because they reported remembering their dreams almost every day, whereas the other half, low recallers, said they only remembered their dreams once or twice a month.
When asleep, both groups showed similar changes in brain activity in response to hearing their names, which were played quietly enough not to wake them.
However, when awake, high recallers showed a more sustained decrease in a brain wave called the alpha wave when they heard their names, compared with the low recallers.
"It was quite surprising to see a difference between the groups during wakefulness," said study researcher Perrine Ruby, neuroscientist at Lyon Neuroscience Research Center in France.
The difference could reflect variations in the brains of high and low recallers that could have a role in how they dream, too, Ruby said.
Who remembers their dreams
A well-established theory suggests that a decrease in the alpha wave is a sign that brain regions are being inhibited from responding to outside stimuli. Studies show that when people hear a sudden sound or open their eyes, and more brain regions become active, the alpha wave is reduced.
In the study, as predicted, both groups showed a decrease in the alpha wave when they heard their names while awake. But high recallers showed a more prolonged decrease, which may be a sign their brains became more widely activated when they heard their names.
In other words, high recallers may engage more brain regions when processing sounds while awake, compared with low recallers, the researchers said.
While people are asleep, the alpha wave behaves in the opposite way —it increases when a sudden sound is heard. Scientists aren’t certain why this happens, but one idea is that it protects the brain from being interrupted by sounds during sleep, Ruby said.
Indeed, the study participants showed an increase in the alpha wave in response to sounds during sleep, and there was no difference between the groups.
One possibility to explain the lack of difference, the researchers said, could be that perhaps high recallers had a larger increase in alpha waves, but it was so high that they woke up.
Time spent awake, during the night
The researchers saw that high recallers awoke more frequently during the night. They were awake, on average, for 30 minutes during the night, whereas low recallers were awake for 14 minutes. However, Ruby said “both figures are in the normal range, it’s not that there’s something wrong with either group.”
Altogether, the results suggest the brain of high recallers may be more reactive to stimuli such as sounds, which could make them wake up more easily. It is more likely a person would remember their dreams if they are awakened immediately after one, Ruby said.
However, waking up at night can account for only a part of the differences people show in remembering dreams. “There’s still much more to understand,” she said.
The study is published online (Aug. 13) in the journal Frontiers in Psychology.
Remembering to Remember Supported by Two Distinct Brain Processes
You plan on shopping for groceries later and you tell yourself that you have to remember to take the grocery bags with you when you leave the house. Lo and behold, you reach the check-out counter and you realize you’ve forgotten the bags.
Remembering to remember — whether it’s grocery bags, appointments, or taking medications — is essential to our everyday lives. New research sheds light on two distinct brain processes that underlie this type of memory, known as prospective memory.
The research is published in Psychological Science, a journal of the Association for Psychological Science.
To investigate how prospective memory is processed in the brain, psychological scientist Mark McDaniel of Washington University in St. Louis and colleagues had participants lie in an fMRI scanner and asked them to press one of two buttons to indicate whether a word that popped up on a screen was a member of a designated category. In addition to this ongoing activity, participants were asked to try to remember to press a third button whenever a special target popped up. The task was designed to tap into participants’ prospective memory, or their ability to remember to take certain actions in response to specific future events.
When McDaniel and colleagues analyzed the fMRI data, they observed that two distinct brain activation patterns emerged when participants made the correct button press for a special target.
When the special target was not relevant to the ongoing activity — such as a syllable like “tor” — participants seemed to rely on top-down brain processes supported by the prefrontal cortex. In order to answer correctly when the special syllable flashed up on the screen, the participants had to sustain their attention and monitor for the special syllable throughout the entire task. In the grocery bag scenario, this would be like remembering to bring the grocery bags by constantly reminding yourself that you can’t forget them.
When the special target was integral to the ongoing activity—such as a whole word, like “table” — participants recruited a different set of brain regions, and they didn’t show sustained activation in these regions. The findings suggest that remembering what to do when the special target was a whole word didn’t require the same type of top-down monitoring. Instead, the target word seemed to act as an environmental cue that prompted participants to make the appropriate response – like reminding yourself to bring the grocery bags by leaving them near the front door.
“These findings suggest that people could make use of several different strategies to accomplish prospective memory tasks,” says McDaniel.
McDaniel and colleagues are continuing their research on prospective memory, examining how this phenomenon might change with age.
(Image: Shutterstock)
Researchers at Johns Hopkins have uncovered a protein switch that can either increase or decrease memory-building activity in brain cells, depending on the signals it detects. Its dual role means the protein is key to understanding the complex network of signals that shapes our brain’s circuitry, the researchers say. A description of their discovery appears in the July 31 issue of the Journal of Neuroscience.
“What’s interesting about this protein, AGAP3, is that it is effectively double-sided: One side beefs up synapses in response to brain activity, while the other side helps bring synapse-building back down to the brain’s resting state,” says Richard Huganir, Ph.D., a professor and director of the Solomon H. Snyder Department of Neuroscience at the Johns Hopkins University School of Medicine and co-director of the Brain Science Institute at Johns Hopkins. “The fact that it links these two opposing activities indicates AGAP3 may turn out to be central to controlling the strength of synapses.”
Huganir has long studied how connections between brain cells, known as synapses, are strengthened and weakened to form or erase memories. The new discovery came about when he and postdoctoral fellow Yuko Oku, Ph.D., investigated the chain reaction of signals involved in one type of synaptic strengthening.
In a study of the proteins that interact with one of the known proteins from that chain reaction, the previously unknown AGAP3 turned up. It contained not only a site designed to bind another protein involved in the chain reaction that leads from brain stimulation to learning, but also a second site involved in bringing synapse-building activity down to normal levels after a burst of activity.
Although it might seem the two different functions are behaving at cross-purposes, Oku says, it also could be that nature’s bundling of these functions together in a single protein is an elegant way of enabling learning and memory while preventing dangerous overstimulation. More research is needed, Oku says, to figure out whether AGAP3’s two sites coordinate by affecting each other’s activity, or are effectively free agents.
The synapses in the brain act as key communication points between approximately one hundred billion neurons. They form a complex network connecting various centres in the brain through electrical impulses.
New research from Lund University suggests that it is precisely here, in the synapses, that Huntington’s disease might begin.
The researchers looked into the brains of mice with real-time imaging methods, following some of the very first stages of the disease through advanced microscopes. What they discovered was an unprecedented degradation of synaptic activity. Long before the well documented nerve cell death, synapses that are important for communication between brain centres that control memory and learning begin to wither. This process has never been mapped before and could be an important step towards understanding the serious non-motor symptoms that affect Huntington patients long before the movement disorders start to show.
“With the naked eye, we have now been able to follow the step by step events when these synapses start to break down. If we are to halt or reverse this process in the future, it is necessary to understand exactly what happens in the initial phase of the disease. Now we know more”, says Professor Jia-Yi Li, the research group leader.
Huntington’s disease has long been characterized by the involuntary writhing movements faced by patients. But in fact, Huntington’s has a very broad and highly individual symptomatology. Depression, memory loss and sleep disorders are all common early on in the disease.
“Many patients testify that these symptoms affect quality of life significantly more than the involuntary jerky movements. Therefore, it is extremely important that we achieve progress in this field of research. Our goal now is to find new therapies that can increase the lifespan of these synapses and maintain their vital function”, explains postdoc Reena, who lead the imaging experiments.
(Source: lunduniversity.lu.se)
Sense of smell: The nose and the brain make quite a team… in disconnection
Alan Carleton’s team from the Neuroscience Department at the University of Geneva (UNIGE) Faculty of Medicine has just shown that the representation of an odor evolves after the first breath, and that an olfactory retentivity persists at the central level. The phenomenon is comparable to what occurs in other sensory systems, such as vision or hearing. These movements undoubtedly enable the identification of new odors in complex environments or participate in the process of odor memorization. This research is the subject of a publication in the latest online edition of the journal PNAS (Proceedings of the National Academy of Sciences of the United States of America).
Rodents can identify odors in a single breath, which is why research on sense of smell in mammals focuses on that first inhalation. Yet we must remember that from a neurological standpoint, sensory representations change during and after the stimuli. To understand the evolution of these mental representations, an international team of researchers led by Professor Alan Carleton at the University of Geneva (UNIGE) Faculty of Medicine conducted the following experiment: by observing the brain of an alert mouse, the neuroscientists recorded the electrical activity emitted by the olfactory bulb of animals inhaling odors.
They were surprised to find that in mitral cells, some representations evolved during the first inhalations, and others persisted and remained stable well after the odor ceased. The cohort subjected to these analyses revealed that the post-odor responses contained an odor retentivity—a specific piece of information about the nature of odor and its concentration.
Will odor memory soon be understood?
Using cerebral imaging, researchers discovered that the majority of sensory activity is visible only during the presentation of odors, which implies that retentivity is essentially internal to the brain. Therefore, odor retentivity would not be dependent upon odorous physicochemical properties. Finally, to artificially induce retentivity, the team photostimulated mitral cells using channelrhodopsin, then recorded the persistent activity maintained at the central level. The strength and persistence of the retentivity were found to be dependent on the duration of the stimulation, both artificial and natural.
In summary, the neuroscientists were able to show that the representation of an odor changes after the first breath, and that an olfactory retentivity persists at the central level, a phenomenon comparable to what occurs in other sensory systems, such as vision and hearing. These movements undoubtedly enable the identification of new odors in complex environments or participate in the process of odor memorization.
(Image: photos.com)
If you forget where you put your car keys and you can’t seem to remember things as well as you used to, the problem may well be with the GluN2B subunits in your NMDA receptors.
And don’t be surprised if by tomorrow you can’t remember the name of those darned subunits.
They help you remember things, but you’ve been losing them almost since the day you were born, and it’s only going to get worse. An old adult may have only half as many of them as a younger person.
Research on these biochemical processes in the Linus Pauling Institute at Oregon State University is making it clear that cognitive decline with age is a natural part of life, and scientists are tracking the problem down to highly specific components of the brain. Separate from some more serious problems like dementia and Alzheimer’s disease, virtually everyone loses memory-making and cognitive abilities as they age. The process is well under way by the age of 40 and picks up speed after that.
But of considerable interest: It may not have to be that way.
“These are biological processes, and once we fully understand what is going on, we may be able to slow or prevent it,” said Kathy Magnusson, a neuroscientist in the OSU Department of Biomedical Sciences, College of Veterinary Medicine, and professor in the Linus Pauling Institute. “There may be ways to influence it with diet, health habits, continued mental activity or even drugs.”
The processes are complex. In a study just published in the Journal of Neuroscience, researchers found that one protein that stabilizes receptors in a young animal – a good thing conducive to learning and memory – can have just the opposite effect if there’s too much of it in an older animal.
But complexity aside, progress is being made. In recent research, supported by the National Institutes of Health, OSU scientists used a genetic therapy in laboratory mice, in which a virus helped carry complementary DNA into appropriate cells and restored some GluN2B subunits. Tests showed that it helped mice improve their memory and cognitive ability.
The NMDA receptor has been known of for decades, Magnusson said. It plays a role in memory and learning but isn’t active all the time – it takes a fairly strong stimulus of some type to turn it on and allow you to remember something. The routine of getting dressed in the morning is ignored and quickly lost to the fog of time, but the day you had an auto accident earns a permanent etching in your memory.
Within the NMDA receptor are various subunits, and Magnusson said that research keeps pointing back to the GluN2B subunit as one of the most important. Infants and children have lots of them, and as a result are like a sponge in soaking up memories and learning new things. But they gradually dwindle in number with age, and it also appears the ones that are left work less efficiently.
“You can still learn new things and make new memories when you are older, but it’s not as easy,” Magnusson said. “Fewer messages get through, fewer connections get made, and your brain has to work harder.”
Until more specific help is available, she said, some of the best advice for maintaining cognitive function is to keep using your brain. Break old habits, do things different ways. Get physical exercise, maintain a good diet and ensure social interaction. Such activities help keep these “subunits” active and functioning.
Gene therapy such as that already used in mice would probably be a last choice for humans, rather than a first option, Magnusson said. Dietary or drug options would be explored first.
“The one thing that does seem fairly clear is that cognitive decline is not inevitable,” she said. “It’s biological, we’re finding out why it happens, and it appears there are ways we might be able to slow or stop it, perhaps repair the NMDA receptors. If we can determine how to do that without harm, we will.”
(Source: oregonstate.edu)
Exercise May be the Best Medicine for Alzheimer’s
New research out of the University of Maryland School of Public Health shows that exercise may improve cognitive function in those at risk for Alzheimer’s by improving the efficiency of brain activity associated with memory. Memory loss leading to Alzheimer’s disease is one of the greatest fears among older Americans. While some memory loss is normal and to be expected as we age, a diagnosis of mild cognitive impairment, or MCI, signals more substantial memory loss and a greater risk for Alzheimer’s, for which there currently is no cure.
The study, led by Dr. J. Carson Smith, assistant professor in the Department of Kinesiology, provides new hope for those diagnosed with MCI. It is the first to show that an exercise intervention with older adults with mild cognitive impairment (average age 78) improved not only memory recall, but also brain function, as measured by functional neuroimaging (via fMRI). The findings are published in the Journal of Alzheimer’s Disease.
“We found that after 12 weeks of being on a moderate exercise program, study participants improved their neural efficiency – basically they were using fewer neural resources to perform the same memory task,” says Dr. Smith. “No study has shown that a drug can do what we showed is possible with exercise.”
Recommended Daily Activity: Good for the Body, Good for the Brain
Two groups of physically inactive older adults (ranging from 60-88 years old) were put on a 12-week exercise program that focused on regular treadmill walking and was guided by a personal trainer. Both groups – one which included adults with MCI and the other with healthy brain function – improved their cardiovascular fitness by about ten percent at the end of the intervention. More notably, both groups also improved their memory performance and showed enhanced neural efficiency while engaged in memory retrieval tasks.
The good news is that these results were achieved with a dose of exercise consistent with the physical activity recommendations for older adults. These guidelines urge moderate intensity exercise (activity that increases your heart rate and makes you sweat, but isn’t so strenuous that you can’t hold a conversation while doing it) on most days for a weekly total of 150 minutes.
Measuring Exercise’s Impact on Brain Health and Memory
One of the first observable symptoms of Alzheimer’s disease is the inability to remember familiar names. Smith and colleagues had study participants identify famous names and measured their brain activation while engaged in correctly recognizing a name – e.g., Frank Sinatra, or other celebrities well known to adults born in the 1930s and 40s. “The task gives us the ability to see what is going on in the brain when there is a correct memory performance,” Smith explains.
Tests and imaging were performed both before and after the 12-week exercise intervention. Brain scans taken after the exercise intervention showed a significant decrease in the intensity of brain activation in eleven brain regions while participants correctly identified famous names. The brain regions with improved efficiency corresponded to those involved in the pathology of Alzheimer’s disease, including the precuneus region, the temporal lobe, and the parahippocampal gyrus.
The exercise intervention was also effective in improving word recall via a “list learning task,” i.e., when people were read a list of 15 words and asked to remember and repeat as many words as possible on five consecutive attempts, and again after a distraction of being given another list of words.
“People with MCI are on a very sharp decline in their memory function, so being able to improve their recall is a very big step in the right direction,” Smith states.
The results of Smith’s study suggest that exercise may reduce the need for over-activation of the brain to correctly remember something. That is encouraging news for those who are looking for something they can do to help preserve brain function.
Dr. Smith has plans for a larger study that would include more participants, including those who are healthy but have a genetic risk for Alzheimer’s, and follow them for a longer time period with exercise in comparison to other types of treatments. He and his team hope to learn more about the impact of exercise on brain function and whether it could delay the onset or progression of Alzheimer’s disease.
Neuroscientists plant false memories in the brain
The phenomenon of false memory has been well-documented: In many court cases, defendants have been found guilty based on testimony from witnesses and victims who were sure of their recollections, but DNA evidence later overturned the conviction.
In a step toward understanding how these faulty memories arise, MIT neuroscientists have shown that they can plant false memories in the brains of mice. They also found that many of the neurological traces of these memories are identical in nature to those of authentic memories.
“Whether it’s a false or genuine memory, the brain’s neural mechanism underlying the recall of the memory is the same,” says Susumu Tonegawa, the Picower Professor of Biology and Neuroscience and senior author of a paper describing the findings in the July 25 edition of Science.
The study also provides further evidence that memories are stored in networks of neurons that form memory traces for each experience we have — a phenomenon that Tonegawa’s lab first demonstrated last year.
Neuroscientists have long sought the location of these memory traces, also called engrams. In the pair of studies, Tonegawa and colleagues at MIT’s Picower Institute for Learning and Memory showed that they could identify the cells that make up part of an engram for a specific memory and reactivate it using a technology called optogenetics.
Lead authors of the paper are graduate student Steve Ramirez and research scientist Xu Liu. Other authors are technical assistant Pei-Ann Lin, research scientist Junghyup Suh, and postdocs Michele Pignatelli, Roger Redondo and Tomas Ryan.
Seeking the engram
Episodic memories — memories of experiences — are made of associations of several elements, including objects, space and time. These associations are encoded by chemical and physical changes in neurons, as well as by modifications to the connections between the neurons.
Where these engrams reside in the brain has been a longstanding question in neuroscience. “Is the information spread out in various parts of the brain, or is there a particular area of the brain in which this type of memory is stored? This has been a very fundamental question,” Tonegawa says.
In the 1940s, Canadian neurosurgeon Wilder Penfield suggested that episodic memories are located in the brain’s temporal lobe. When Penfield electrically stimulated cells in the temporal lobes of patients who were about to undergo surgery to treat epileptic seizures, the patients reported that specific memories popped into mind. Later studies of the amnesiac patient known as “H.M.” confirmed that the temporal lobe, including the area known as the hippocampus, is critical for forming episodic memories.
However, these studies did not prove that engrams are actually stored in the hippocampus, Tonegawa says. To make that case, scientists needed to show that activating specific groups of hippocampal cells is sufficient to produce and recall memories.
To achieve that, Tonegawa’s lab turned to optogenetics, a new technology that allows cells to be selectively turned on or off using light.
For this pair of studies, the researchers engineered mouse hippocampal cells to express the gene for channelrhodopsin, a protein that activates neurons when stimulated by light. They also modified the gene so that channelrhodopsin would be produced whenever the c-fos gene, necessary for memory formation, was turned on.
In last year’s study, the researchers conditioned these mice to fear a particular chamber by delivering a mild electric shock. As this memory was formed, the c-fos gene was turned on, along with the engineered channelrhodopsin gene. This way, cells encoding the memory trace were “labeled” with light-sensitive proteins.
The next day, when the mice were put in a different chamber they had never seen before, they behaved normally. However, when the researchers delivered a pulse of light to the hippocampus, stimulating the memory cells labeled with channelrhodopsin, the mice froze in fear as the previous day’s memory was reactivated.
“Compared to most studies that treat the brain as a black box while trying to access it from the outside in, this is like we are trying to study the brain from the inside out,” Liu says. “The technology we developed for this study allows us to fine-dissect and even potentially tinker with the memory process by directly controlling the brain cells.”
Incepting false memories
That is exactly what the researchers did in the new study — exploring whether they could use these reactivated engrams to plant false memories in the mice’s brains.
First, the researchers placed the mice in a novel chamber, A, but did not deliver any shocks. As the mice explored this chamber, their memory cells were labeled with channelrhodopsin. The next day, the mice were placed in a second, very different chamber, B. After a while, the mice were given a mild foot shock. At the same instant, the researchers used light to activate the cells encoding the memory of chamber A.
On the third day, the mice were placed back into chamber A, where they now froze in fear, even though they had never been shocked there. A false memory had been incepted: The mice feared the memory of chamber A because when the shock was given in chamber B, they were reliving the memory of being in chamber A.
Moreover, that false memory appeared to compete with a genuine memory of chamber B, the researchers found. These mice also froze when placed in chamber B, but not as much as mice that had received a shock in chamber B without having the chamber A memory activated.
The researchers then showed that immediately after recall of the false memory, levels of neural activity were also elevated in the amygdala, a fear center in the brain that receives memory information from the hippocampus, just as they are when the mice recall a genuine memory.
These two papers represent a major step forward in memory research, says Howard Eichenbaum, a professor of psychology and director of Boston University’s Center for Memory and Brain.
“They identified a neural network associated with experience in an environment, attached a fear association with it, then reactivated the network to show that it supports memory expression. That, to me, shows for the first time a true functional engram,” says Eichenbaum, who was not part of the research team.
The MIT team is now planning further studies of how memories can be distorted in the brain.
“Now that we can reactivate and change the contents of memories in the brain, we can begin asking questions that were once the realm of philosophy,” Ramirez says. “Are there multiple conditions that lead to the formation of false memories? Can false memories for both pleasurable and aversive events be artificially created? What about false memories for more than just contexts — false memories for objects, food or other mice? These are the once seemingly sci-fi questions that can now be experimentally tackled in the lab.”
New technique can rapidly turn genes on and off, helping scientists better understand their function.
Although human cells have an estimated 20,000 genes, only a fraction of those are turned on at any given time, depending on the cell’s needs — which can change by the minute or hour. To find out what those genes are doing, researchers need tools that can manipulate their status on similarly short timescales.
That is now possible, thanks to a new technology developed at MIT and the Broad Institute that can rapidly start or halt the expression of any gene of interest simply by shining light on the cells.
The work is based on a technique known as optogenetics, which uses proteins that change their function in response to light. In this case, the researchers adapted the light-sensitive proteins to either stimulate or suppress the expression of a specific target gene almost immediately after the light comes on.
“Cells have very dynamic gene expression happening on a fairly short timescale, but so far the methods that are used to perturb gene expression don’t even get close to those dynamics. To understand the functional impact of those gene-expression changes better, we have to be able to match the naturally occurring dynamics as closely as possible,” says Silvana Konermann, an MIT graduate student in brain and cognitive sciences.
The ability to precisely control the timing and duration of gene expression should make it much easier to figure out the roles of particular genes, especially those involved in learning and memory. The new system can also be used to study epigenetic modifications — chemical alterations of the proteins that surround DNA — which are also believed to play an important role in learning and memory.
Konermann and Mark Brigham, a graduate student at Harvard University, are the lead authors of a paper describing the technique in the July 22 online edition of Nature. The paper’s senior author is Feng Zhang, the W.M. Keck Assistant Professor in Biomedical Engineering at MIT and a core member of the Broad Institute and MIT’s McGovern Institute for Brain Research.
Shining light on genes
The new system consists of several components that interact with each other to control the copying of DNA into messenger RNA (mRNA), which carries genetic instructions to the rest of the cell. The first is a DNA-binding protein known as a transcription activator-like effector (TALE). TALEs are modular proteins that can be strung together in a customized way to bind any DNA sequence.
Fused to the TALE protein is a light-sensitive protein called CRY2 that is naturally found in Arabidopsis thaliana, a small flowering plant. When light hits CRY2, it changes shape and binds to its natural partner protein, known as CIB1. To take advantage of this, the researchers engineered a form of CIB1 that is fused to another protein that can either activate or suppress gene copying.
After the genes for these components are delivered to a cell, the TALE protein finds its target DNA and wraps around it. When light shines on the cells, the CRY2 protein binds to CIB1, which is floating in the cell. CIB1 brings along a gene activator, which initiates transcription, or the copying of DNA into mRNA. Alternatively, CIB1 could carry a repressor, which shuts off the process.
A single pulse of light is enough to stimulate the protein binding and initiate DNA copying. The researchers found that pulses of light delivered every minute or so are the most effective way to achieve continuous transcription for the desired period of time. Within 30 minutes of light delivery, the researchers detected an uptick in the amount of mRNA being produced from the target gene. Once the pulses stop, the mRNA starts to degrade within about 30 minutes.
In this study, the researchers tried targeting nearly 30 different genes, both in neurons grown in the lab and in living animals. Depending on the gene targeted and how much it is normally expressed, the researchers were able to boost transcription by a factor of two to 200.
Karl Deisseroth, a professor of bioengineering at Stanford University and one of the inventors of optogenetics, says the most important innovation of the technique is that it allows control of genes that naturally occur in the cell, as opposed to engineered genes delivered by scientists.
“You could control, at precise times, a particular genetic locus and see how everything responds to that, with high temporal precision,” says Deisseroth, who was not part of the research team.
Epigenetic modifications
Another important element of gene-expression control is epigenetic modification. One major class of epigenetic effectors is chemical modification of the proteins, known as histones, that anchor chromosomal DNA and control access to the underlying genes. The researchers showed that they can also alter these epigenetic modifications by fusing TALE proteins with histone modifiers.
Epigenetic modifications are thought to play a key role in learning and forming memories, but this has not been very well explored because there are no good ways to disrupt the modifications, short of blocking histone modification of the entire genome. The new technique offers a much more precise way to interfere with modifications of individual genes.
“We want to allow people to prove the causal role of specific epigenetic modifications in the genome,” Zhang says.
So far, the researchers have demonstrated that some of the histone effector domains can be tethered to light-sensitive proteins; they are now trying to expand the types of histone modifiers they can incorporate into the system.
“It would be really useful to expand the number of epigenetic marks that we can control. At the moment we have a successful set of histone modifications, but there are a good deal more of them that we and others are going to want to be able to use this technology for,” Brigham says.
(Source: web.mit.edu)
Finding shows oxytocin strengthens bad memories and can increase fear and anxiety
It turns out the love hormone oxytocin is two-faced. Oxytocin has long been known as the warm, fuzzy hormone that promotes feelings of love, social bonding and well-being. It’s even being tested as an anti-anxiety drug. But new Northwestern Medicine® research shows oxytocin also can cause emotional pain, an entirely new, darker identity for the hormone.
Oxytocin appears to be the reason stressful social situations, perhaps being bullied at school or tormented by a boss, reverberate long past the event and can trigger fear and anxiety in the future.
That’s because the hormone actually strengthens social memory in one specific region of the brain, Northwestern scientists discovered.
If a social experience is negative or stressful, the hormone activates a part of the brain that intensifies the memory. Oxytocin also increases the susceptibility to feeling fearful and anxious during stressful events going forward.
(Presumably, oxytocin also intensifies positive social memories and, thereby, increases feelings of well being, but that research is ongoing.)
The findings are important because chronic social stress is one of the leading causes of anxiety and depression, while positive social interactions enhance emotional health. The research, which was done in mice, is particularly relevant because oxytocin currently is being tested as an anti-anxiety drug in several clinical trials.
“By understanding the oxytocin system’s dual role in triggering or reducing anxiety, depending on the social context, we can optimize oxytocin treatments that improve well-being instead of triggering negative reactions,” said Jelena Radulovic, the senior author of the study and the Dunbar Professsor of Bipolar Disease at Northwestern University Feinberg School of Medicine. The paper was published July 21 in Nature Neuroscience.
This is the first study to link oxytocin to social stress and its ability to increase anxiety and fear in response to future stress. Northwestern scientists also discovered the brain region responsible for these effects — the lateral septum – and the pathway or route oxytocin uses in this area to amplify fear and anxiety.
The scientists discovered that oxytocin strengthens negative social memory and future anxiety by triggering an important signaling molecule — ERK (extracellular signal regulated kinases) — that becomes activated for six hours after a negative social experience. ERK causes enhanced fear, Radulovic believes, by stimulating the brain’s fear pathways, many of which pass through the lateral septum. The region is involved in emotional and stress responses.
The findings surprised the researchers, who were expecting oxytocin to modulate positive emotions in memory, based on its long association with love and social bonding.
“Oxytocin is usually considered a stress-reducing agent based on decades of research,” said Yomayra Guzman, a doctoral student in Radulovic’s lab and the study’s lead author. “With this novel animal model, we showed how it enhances fear rather than reducing it and where the molecular changes are occurring in our central nervous system.’
The new research follows three recent human studies with oxytocin, all of which are beginning to offer a more complicated view of the hormone’s role in emotions.
All the new experiments were done in the lateral septum. This region has the highest oxytocin levels in the brain and has high levels of oxytocin receptors across all species from mice to humans.
“This is important because the variability of oxytocin receptors in different species is huge,” Radulovic said. “We wanted the research to be relevant for humans, too.”
Experiments with mice in the study established that 1) oxytocin is essential for strengthening the memory of negative social interactions and 2) oxytocin increases fear and anxiety in future stressful situations.
Experiment 1: Oxytocin Strengthens Bad Memories
Three groups of mice were individually placed in cages with aggressive mice and experienced social defeat, a stressful experience for them. One group was missing its oxytocin receptors, essentially the plug by which the hormone accesses brain cells. The lack of receptors means oxytocin couldn’t enter the mice’s brain cells. The second group had an increased number of receptors so their brain cells were flooded with the hormone. The third control group had a normal number of receptors.
Six hours later, the mice were returned to cages with the aggressive mice. The mice that were missing their oxytocin receptors didn’t appear to remember the aggressive mice and show any fear. Conversely, when mice with increased numbers of oxytocin receptors were reintroduced to the aggressive mice, they showed an intense fear reaction and avoided the aggressive mice.
Experiment 2: Oxytocin Increases Fear and Anxiety in Future Stress
Again, the three groups of mice were exposed to the stressful experience of social defeat in the cages of other more aggressive mice. This time, six hours after the social stress, the mice were put in a box in which they received a brief electric shock, which startles them but is not painful. Then 24 hours later, the mice were returned to the same box but did not receive a shock.
The mice missing their oxytocin receptors did not show any enhanced fear when they re-entered the box in which they received the shock. The second group, which had extra oxytocin receptors showed much greater fear in the box. The third control group exhibited an average fear response.
“This experiment shows that after a negative social experience the oxytocin triggers anxiety and fear in a new stressful situation,” Radulovic said.
(Source: northwestern.edu)