Neuroscience

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Posts tagged memory consolidation

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Sleep Mechanism Identified That Plays Role in Emotional Memory

Sleep researchers from University of California campuses in Riverside and San Diego have identified the sleep mechanism that enables the brain to consolidate emotional memory and found that a popular prescription sleep aid heightens the recollection of and response to negative memories.

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Their findings have implications for individuals suffering from insomnia related to posttraumatic stress disorder (PTSD) and other anxiety disorders who are prescribed zolpidem (Ambien) to help them sleep.

The study — “Pharmacologically Increasing Sleep Spindles Enhances Recognition for Negative and High-arousal Memories” — appears in the Journal of Cognitive Neuroscience. It was funded by a National Institutes of Health career award to Sara C. Mednick, assistant professor of psychology at UC Riverside, of $651,999 over five years.

Mednick and UC San Diego psychologists Erik J. Kaestner and John T. Wixted determined that a sleep feature known as sleep spindles — bursts of brain activity that last for a second or less during a specific stage of sleep — are important for emotional memory.

Research Mednick published earlier this year demonstrated the critical role that sleep spindles play in consolidating information from short-term to long-term memory in the hippocampus, located in the cerebral cortex of the brain. Zolpidem enhanced the process, a discovery that could lead to new sleep therapies to improve memory for aging adults and those with dementia, Alzheimer’s and schizophrenia. It was the first study to show that sleep can be manipulated with pharmacology to improve memory.

“We know that sleep spindles are involved in declarative memory — explicit information we recall about the world, such as places, people and events, ” she explained.

But until now, researchers had not considered sleep spindles as playing a role in emotional memory , focusing instead on rapid eye movement (REM) sleep.

Using two commonly prescribed sleep aids — zolpidem and sodium oxybate (Xyrem) — Mednick, Kaestner and Wixted were able to tease apart the effects of sleep spindles and rapid eye movement (REM) sleep on the recall of emotional memories. They determined that sleep spindles, not REM, affect emotional memory.

The researchers gave zolpidem, sodium oxybate (Xyrem) and a placebo to 28 men and women between the ages of 18 and 39 who were normal sleepers, allowing several days between doses to allow the pharmaceuticals to leave their bodies. The participants viewed standardized images known to elicit positive and negative responses for one second before and after taking supervised naps. They recalled more images that had negative or highly arousing content after taking zolpidem, a finding that also suggests that the brain may favor consolidation of negative memories, she said.

“I was surprised by the specificity of the results, that the emotional memory improvement was specifically for the negative and high-arousal memories, and the ramifications of these results for people with anxiety disorders and PTSD,” Mednick said. “These are people who already have heightened memory for negative and high-arousal memories. Sleep drugs might be improving their memories for things they don’t want to remember.”

The study may have even broader implications, the researchers said. Clinical guidelines of the U.S. Department of Veterans Affairs and Department of Defense recommend against the routine use of benzodiazepines to treat PTSD, although their use increased among men and women with PTSD between 2003 and 2010. The effects of benzodiazepines on sleep are similar to those of zolpidem.

The U.S. Air Force uses zolpidem as one of the prescribed “no-go pills” to help flight crews calm down after taking stimulants to stay awake during long missions, the researchers noted in the study.

“In light of the present results, it would be worthwhile to investigate whether the administration of benzodiazepine-like drugs may be increasing the retention of highly arousing and negative memories, which would have a countertherapeutic effect,” they wrote. “Further research on the relationship between hypnotics and emotional mood disorders would seem to be in order.”

(Source: ucrtoday.ucr.edu)

Filed under sleep memory consolidation emotional memory sleep spindles hippocampus psychology neuroscience science

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Sleep Promotes Consolidation of Emotional Memory in Healthy Children but Not in Children with Attention-Deficit Hyperactivity Disorder 
Fronto-limbic brain activity during sleep is believed to support the consolidation of emotional memories in healthy adults. Attention deficit-hyperactivity disorder (ADHD) is accompanied by emotional deficits coincidently caused by dysfunctional interplay of fronto-limbic circuits. This study aimed to examine the role of sleep in the consolidation of emotional memory in ADHD in the context of healthy development. 16 children with ADHD, 16 healthy children, and 20 healthy adults participated in this study. Participants completed an emotional picture recognition paradigm in sleep and wake control conditions. Each condition had an immediate (baseline) and delayed (target) retrieval session. The emotional memory bias was baseline–corrected, and groups were compared in terms of sleep-dependent memory consolidation (sleep vs. wake). We observed an increased sleep-dependent emotional memory bias in healthy children compared to children with ADHD and healthy adults. Frontal oscillatory EEG activity (slow oscillations, theta) during sleep correlated negatively with emotional memory performance in children with ADHD. When combining data of healthy children and adults, correlation coefficients were positive and differed from those in children with ADHD. Since children displayed a higher frontal EEG activity than adults these data indicate a decline in sleep-related consolidation of emotional memory in healthy development. In addition, it is suggested that deficits in sleep-related selection between emotional and non-emotional memories in ADHD exacerbate emotional problems during daytime as they are often reported in ADHD.

Sleep Promotes Consolidation of Emotional Memory in Healthy Children but Not in Children with Attention-Deficit Hyperactivity Disorder

Fronto-limbic brain activity during sleep is believed to support the consolidation of emotional memories in healthy adults. Attention deficit-hyperactivity disorder (ADHD) is accompanied by emotional deficits coincidently caused by dysfunctional interplay of fronto-limbic circuits. This study aimed to examine the role of sleep in the consolidation of emotional memory in ADHD in the context of healthy development. 16 children with ADHD, 16 healthy children, and 20 healthy adults participated in this study. Participants completed an emotional picture recognition paradigm in sleep and wake control conditions. Each condition had an immediate (baseline) and delayed (target) retrieval session. The emotional memory bias was baseline–corrected, and groups were compared in terms of sleep-dependent memory consolidation (sleep vs. wake). We observed an increased sleep-dependent emotional memory bias in healthy children compared to children with ADHD and healthy adults. Frontal oscillatory EEG activity (slow oscillations, theta) during sleep correlated negatively with emotional memory performance in children with ADHD. When combining data of healthy children and adults, correlation coefficients were positive and differed from those in children with ADHD. Since children displayed a higher frontal EEG activity than adults these data indicate a decline in sleep-related consolidation of emotional memory in healthy development. In addition, it is suggested that deficits in sleep-related selection between emotional and non-emotional memories in ADHD exacerbate emotional problems during daytime as they are often reported in ADHD.

Filed under brain activity ADHD emotional memory memory consolidation neuroscience science

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Musicians who learn a new melody demonstrate enhanced skill after a night’s sleep
A new study that examined how the brain learns and retains motor skills provides insight into musical skill.
Performance of a musical task improved among pianists whose practice of a new melody was followed by a night of sleep, says researcher Sarah E. Allen, Southern Methodist University, Dallas.
The study is among the first to look at whether sleep enhances the learning process for musicians practicing a new piano melody.
The study found, however, that when two similar melodies were practiced one after the other, followed by sleep, any gains in speed and accuracy achieved during practice diminished overnight, said Allen, an assistant professor of music education in SMU’s Meadows School of the Arts.
“The goal is to understand how the brain decides what to keep, what to discard, what to enhance, because our brains are receiving such a rich data stream and we don’t have room for everything,” Allen said. “I was fascinated to study this because as musicians we practice melodies in juxtaposition with one another all the time.”
Surprisingly, in a third result the study found that when two similar musical pieces were practiced one after the other, followed by practice of the first melody again, a night’s sleep enhanced pianists’ skills on the first melody, she said.
“The really unexpected result that I found was that for those subjects who learned the two melodies, if before they left practice they played the first melody again, it seemed to reactivate that memory so that they did improve overnight. Replaying it seemed to counteract the interference of learning a second melody.”
The study adds to a body of research in recent decades that has found the brain keeps processing the learning of a new motor skill even after active training has stopped. That’s also the case during sleep.
The findings may in the future guide the teaching of music, Allen said.
“In any task we want to maximize our time and our effort. This research can ultimately help us practice in an advantageous way and teach in an advantageous way,” Allen said. “There could be pedagogical benefits for the order in which you practice things, but it’s really too early to say. We want to research this further.”
The study, “Memory stabilization and enhancement following music practice,” will be published in the journal Psychology of Music.
New study builds on earlier brain research in rats and humans Researchers in the field of procedural memory consolidation have systematically examined the process in both rats and humans.
Studies have found that after practice of a motor skill, such as running a maze or completing a handwriting task, the areas of the brain activated during practice continue to be active for about four to six hours afterward. Activation occurs whether a subject is, for example, eating, resting, shopping or watching TV, Allen said.
Also, researchers have found that the area of the brain activated during practice of the skill is activated again during sleep, she said, essentially recalling the skill and enhancing and reinforcing it. For motor skills such as finger-tapping a sequence, research found that performance tends to be 10 percent to 13 percent more efficient after sleep, with fewer errors.
“There are two phases of memory consolidation. We refer to the four to six hours after training as stabilization. We refer to the phase during sleep as enhancement,” Allen said. “We know that sleep seems to play a very important role. It makes memories a more permanent, less fragile part of the brain.”
Allen’s finding with musicians that practicing a second melody interfered with retaining the first melody is consistent with a growing number of similar research studies that have found learning a second motor skill task interferes with enhancement of the first task.
Impact of sleep on learning for musicians For Allen’s study, 60 undergraduate and graduate music majors participated in the research.
Divided into four groups, each musician practiced either one or both melodies during evening sessions, then returned the next day after sleep to be tested on their performance of the target melody.
The subjects learned the melodies on a Roland digital piano, practicing with their left hand during 12 30-second practice blocks separated by 30-second rest intervals. Software written for the experiment made it possible to digitally recorde musical instrument data from the performances. The number of correct key presses per 30-second block reflected speed and accuracy.
Musicians who learned a single melody showed performance gains on the test the next day.
Those who learned a second melody immediately after learning the target melody didn’t get any overnight enhancement in the first melody.
Those who learned two melodies, but practiced the first one again before going home to sleep, showed overnight enhancement when tested on the first melody.
“This was the most surprising finding, and perhaps the most important,” Allen reported in the Psychology of Music. “The brief test of melody A following the learning of melody B at the end of the evening training session seems to have reactivated the memory of melody A in a way that inhibited the interfering effects of learning melody B that were observed in the AB-sleep-A group.”— Margaret Allen

Musicians who learn a new melody demonstrate enhanced skill after a night’s sleep

A new study that examined how the brain learns and retains motor skills provides insight into musical skill.

Performance of a musical task improved among pianists whose practice of a new melody was followed by a night of sleep, says researcher Sarah E. Allen, Southern Methodist University, Dallas.

The study is among the first to look at whether sleep enhances the learning process for musicians practicing a new piano melody.

The study found, however, that when two similar melodies were practiced one after the other, followed by sleep, any gains in speed and accuracy achieved during practice diminished overnight, said Allen, an assistant professor of music education in SMU’s Meadows School of the Arts.

“The goal is to understand how the brain decides what to keep, what to discard, what to enhance, because our brains are receiving such a rich data stream and we don’t have room for everything,” Allen said. “I was fascinated to study this because as musicians we practice melodies in juxtaposition with one another all the time.”

Surprisingly, in a third result the study found that when two similar musical pieces were practiced one after the other, followed by practice of the first melody again, a night’s sleep enhanced pianists’ skills on the first melody, she said.

“The really unexpected result that I found was that for those subjects who learned the two melodies, if before they left practice they played the first melody again, it seemed to reactivate that memory so that they did improve overnight. Replaying it seemed to counteract the interference of learning a second melody.”

The study adds to a body of research in recent decades that has found the brain keeps processing the learning of a new motor skill even after active training has stopped. That’s also the case during sleep.

The findings may in the future guide the teaching of music, Allen said.

“In any task we want to maximize our time and our effort. This research can ultimately help us practice in an advantageous way and teach in an advantageous way,” Allen said. “There could be pedagogical benefits for the order in which you practice things, but it’s really too early to say. We want to research this further.”

The study, “Memory stabilization and enhancement following music practice,” will be published in the journal Psychology of Music.

New study builds on earlier brain research in rats and humans
Researchers in the field of procedural memory consolidation have systematically examined the process in both rats and humans.

Studies have found that after practice of a motor skill, such as running a maze or completing a handwriting task, the areas of the brain activated during practice continue to be active for about four to six hours afterward. Activation occurs whether a subject is, for example, eating, resting, shopping or watching TV, Allen said.

Also, researchers have found that the area of the brain activated during practice of the skill is activated again during sleep, she said, essentially recalling the skill and enhancing and reinforcing it. For motor skills such as finger-tapping a sequence, research found that performance tends to be 10 percent to 13 percent more efficient after sleep, with fewer errors.

“There are two phases of memory consolidation. We refer to the four to six hours after training as stabilization. We refer to the phase during sleep as enhancement,” Allen said. “We know that sleep seems to play a very important role. It makes memories a more permanent, less fragile part of the brain.”

Allen’s finding with musicians that practicing a second melody interfered with retaining the first melody is consistent with a growing number of similar research studies that have found learning a second motor skill task interferes with enhancement of the first task.

Impact of sleep on learning for musicians
For Allen’s study, 60 undergraduate and graduate music majors participated in the research.

Divided into four groups, each musician practiced either one or both melodies during evening sessions, then returned the next day after sleep to be tested on their performance of the target melody.

The subjects learned the melodies on a Roland digital piano, practicing with their left hand during 12 30-second practice blocks separated by 30-second rest intervals. Software written for the experiment made it possible to digitally recorde musical instrument data from the performances. The number of correct key presses per 30-second block reflected speed and accuracy.

Musicians who learned a single melody showed performance gains on the test the next day.

Those who learned a second melody immediately after learning the target melody didn’t get any overnight enhancement in the first melody.

Those who learned two melodies, but practiced the first one again before going home to sleep, showed overnight enhancement when tested on the first melody.

“This was the most surprising finding, and perhaps the most important,” Allen reported in the Psychology of Music. “The brief test of melody A following the learning of melody B at the end of the evening training session seems to have reactivated the memory of melody A in a way that inhibited the interfering effects of learning melody B that were observed in the AB-sleep-A group.”— Margaret Allen

Filed under brain sleep memory memory consolidation musicians music performance psychology neuroscience science

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Reactivating memories during sleep

Why do some memories last a lifetime while others disappear quickly?

image

(Image: Tim Vernon, LTH NHS TRUST/SCIENCE PHOTO LIBRARY)

A new study suggests that memories rehearsed, during either sleep or waking, can have an impact on memory consolidation and on what is remembered later.

The new Northwestern University study shows that when the information that makes up a memory has a high value (associated with, for example, making more money), the memory is more likely to be rehearsed and consolidated during sleep and, thus, be remembered later.

Also, through the use of a direct manipulation of sleep, the research demonstrated a way to encourage the reactivation of low-value memories so they too were remembered later.

Delphine Oudiette, a postdoctoral fellow in the department of psychology at Northwestern and lead author of the study, designed the experiment to study how participants remembered locations of objects on a computer screen. A value assigned to each object informed participants how much money they could make if they remembered it later on the test.

"The pay-off was much higher for some of the objects than for others," explained Ken Paller, professor of psychology at Northwestern and co-author of the study. "In other words, we manipulated the value of the memories — some were valuable memories and others not so much, just as the things we experience each day vary in the extent to which we’d like to be able to remember them later."

When each object was shown, it was accompanied by a characteristic sound. For example, a tea kettle would appear with a whistling sound. During both states of wakefulness and sleep, some of the sounds were played alone, quite softly, essentially reminding participants of the low-value items.

Participants remembered the low-value associations better when the sound presentations occurred during sleep.

"We think that what’s happening during sleep is basically the reactivation of that information," Oudiette said. "We can provoke the reactivation by presenting those sounds, therefore energizing the low-value memories so they get stored better."

The research poses provocative implications about the role memory reactivation during sleep could play in improving memory storage,” said Paller, director of the Cognitive Neuroscience Program at Northwestern. “Whatever makes you rehearse during sleep is going to determine what you remember later, and conversely, what you’re going to forget.”

Many memories that are stored during the day are not remembered.

"We think one of the reasons for that is that we have to rehearse memories in order to keep them. When you practice and rehearse, you increase the likelihood of later remembering," Oudiette said. "And a lot of our rehearsal happens when we don’t even realize it — while we’re asleep."

Paller said selectivity of memory consolidation is not well understood. Most efforts in memory research have focused on what happens when you first form a memory and on what happens when you retrieve a memory.

"The in-between time is what we want to learn more about, because a fascinating aspect of memory storage is that it is not static," Paller said. "Memories in our brain are changing all of the time. Sometimes you improve memory storage by rehearsing all the details, so maybe later you remember better — or maybe worse if you’ve embellished too much.

"The fact that this critical memory reactivation transpires during sleep has mostly been hidden from us, from humanity, because we don’t realize so much of what’s happening while we’re asleep," he said.

(Source: eurekalert.org)

Filed under sleep memory memory consolidation memory storage wakefulness psychology neuroscience science

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Sleep Discovery Could Lead to Therapies That Improve Memory
A team of sleep researchers led by UC Riverside psychologist Sara C. Mednick has confirmed the mechanism that enables the brain to consolidate memory and found that a commonly prescribed sleep aid enhances the process. Those discoveries could lead to new sleep therapies that will improve memory for aging adults and those with dementia, Alzheimer’s and schizophrenia.
The groundbreaking research appears in a paper, “The Critical Role of Sleep Spindles in Hippocampal-Dependent Memory: A Pharmacology Study,” published in the Journal of Neuroscience.
Earlier research found a correlation between sleep spindles — bursts of brain activity that last for a second or less during a specific stage of sleep — and consolidation of memories that depend on the hippocampus. The hippocampus, part of the cerebral cortex, is important in the consolidation of information from short-term to long-term memory, and spatial navigation. The hippocampus is one of the first regions of the brain damaged by Alzheimer’s disease.
Mednick and her research team demonstrated, for the first time, the critical role that sleep spindles play in consolidating memory in the hippocampus, and they showed that pharmaceuticals could significantly improve that process, far more than sleep alone.
In addition to Mednick the research team includes: Elizabeth A. McDevitt, UC San Diego; James K. Walsh, VA San Diego Healthcare System, La Jolla, Calif; Erin Wamsley, St. Luke’s Hospital, St. Louis, Mo.; Martin Paulus, Stanford University; Jennifer C. Kanady, Harvard Medical School; and Sean P.A. Drummond, UC Berkeley.
“We found that a very common sleep drug can be used to increase verbal memory,” said Mednick, the lead author of the paper that outlines results of two studies conducted over five years with a $651,999 research grant from the National Institutes of Health. “This is the first study to show you can manipulate sleep to improve memory. It suggests sleep drugs could be a powerful tool to tailor sleep to particular memory disorders.”
(Image credit)

Sleep Discovery Could Lead to Therapies That Improve Memory

A team of sleep researchers led by UC Riverside psychologist Sara C. Mednick has confirmed the mechanism that enables the brain to consolidate memory and found that a commonly prescribed sleep aid enhances the process. Those discoveries could lead to new sleep therapies that will improve memory for aging adults and those with dementia, Alzheimer’s and schizophrenia.

The groundbreaking research appears in a paper, “The Critical Role of Sleep Spindles in Hippocampal-Dependent Memory: A Pharmacology Study,” published in the Journal of Neuroscience.

Earlier research found a correlation between sleep spindles — bursts of brain activity that last for a second or less during a specific stage of sleep — and consolidation of memories that depend on the hippocampus. The hippocampus, part of the cerebral cortex, is important in the consolidation of information from short-term to long-term memory, and spatial navigation. The hippocampus is one of the first regions of the brain damaged by Alzheimer’s disease.

Mednick and her research team demonstrated, for the first time, the critical role that sleep spindles play in consolidating memory in the hippocampus, and they showed that pharmaceuticals could significantly improve that process, far more than sleep alone.

In addition to Mednick the research team includes: Elizabeth A. McDevitt, UC San Diego; James K. Walsh, VA San Diego Healthcare System, La Jolla, Calif; Erin Wamsley, St. Luke’s Hospital, St. Louis, Mo.; Martin Paulus, Stanford University; Jennifer C. Kanady, Harvard Medical School; and Sean P.A. Drummond, UC Berkeley.

“We found that a very common sleep drug can be used to increase verbal memory,” said Mednick, the lead author of the paper that outlines results of two studies conducted over five years with a $651,999 research grant from the National Institutes of Health. “This is the first study to show you can manipulate sleep to improve memory. It suggests sleep drugs could be a powerful tool to tailor sleep to particular memory disorders.”

(Image credit)

Filed under memory alzheimer's disease brain activity memory consolidation sleep neuroscience science

111 notes

Novel storage mechanism allows command, control of memory
Introductions at a party seemingly go in one ear and out the other. However, if you meet someone two or three times during the party, you are more likely to remember his or her name. Your brain has taken a short-term memory - the introduction - and converted it into a long-term one. The molecular key to this activity is mTORC2 (mammalian target of rapamycin complex 2), according to researchers at Baylor College of Medicine in an article that appeared online in the journal Nature Neuroscience.
"Memory consolidation is a fundamental process," said Dr. Mauro Costa-Mattioli, assistant professor of neuroscience at BCM and corresponding author of the report. "Memories are at the center of our identity. They allow us to remember people, places and events for a long time, even a lifetime. Understanding the precise mechanism by which memories are stored in the brain will lead to the development of new treatments for conditions associated with memory loss".
Actin fibers
For the last five decades, neuroscientists have known that making long-lasting memories is dependent on the ability of brain cells (neurons) to synthesize new proteins. In their studies, Costa-Mattioli and his colleagues found a new mechanism by which memories are stored in the brain. The newly discovered mTORC2 regulates memory formation by modulating actin fibers, an important component of the architectural structure of the neuron.
"These actin fibers allow long-lasting changes in synaptic strength and ultimately long-term memories," said Wei Huang, a BCM graduate student and first author in the study.
Using genetically-engineered mice, the researchers found that turning off mTORC2 in the hippocampus (a crucial region required for memory formation) and surrounding areas allowed the animals to have a normal short-term memory, but prevented them from forming long-term memories. Similar to human patients with injury in the hippocampus, these mutant mice were no longer able to form new long-lasting memories.
According to Costa-Mattioli’s findings, mTORC2’s role is evolutionarily conserved and likely relevant to humans. Like mTORC2-deficient mice, fruit flies lacking TORC2 show defective long-term memory storage.
"Given that flies and mice last shared a common ancestor 500 million years ago, it is quite remarkable and telling that the function of mTORC2 in the regulation of memory is indeed maintained," said Dr. Gregg Roman, director of the Biology of Behavior Institute at the University of Houston, who contributed to the fly experiments.
Form long-term memories
The Holy Grail of memory neuroscience and to a certain extent, of industry efforts to produce a “smart drug,” has been the identification of molecules that promote the formation of long-term memory, said Costa-Mattioli. “We therefore wondered whether by turning on mTORC2 or even actin polymerization itself, we could form long-term memories more easily,” said Dr. Ping Jun Zhu, assistant professor of neuroscience at BCM, co-first author and senior scientist in Costa-Mattioli’s lab.
The team has identified a small molecule (a drug) that by activating mTORC2 and consequently actin polymerization enhances not only the synaptic strength between nerve cells but also long-term memory formation. In addition, the authors found that by directly promoting actin polymerization, with a second drug, long-term memory is generated more easily.
Costa-Mattioli’s team has identified two memory-enhancing drugs, but can they enhance memory in people? It is perhaps too early to say.
Huang said, “mTORC2, as far as we know, is really a new potential target for therapeutic treatments of human disorders. In the next few years, I predict we will see a lot of studies focusing on mTORC2 as a target.”
Memory cocktail
Costa-Mattioli’s short-term goals are to identify human cognitive disorders in which mTORC2 activity is dysfunctional and to see whether its restoration can return to normal impaired memory function in aging or even Alzheimer’s disease. But a small molecule alone might not do the job. Similar to the treatments for HIV or cancer, he believes that a combination of small molecules improving different aspects of memory formation will be required to efficiently treat cognitive disorders.
"We should start thinking about an efficient ‘memory cocktail’ rather than a single ‘memory pill.’ One molecule alone might not be enough. We may be years away from a decisive treatment, but I believe we are definitely on the right path," he said.
Others who took part in this work include Hongyi Zhou, Loredana Stoica and Mauricio Galiano, all of BCM, Krešimir Krnjević of McGill University in Montreal, Canada; and Shixing Zhang of the University of Houston.
(Image: Shutterstock)

Novel storage mechanism allows command, control of memory

Introductions at a party seemingly go in one ear and out the other. However, if you meet someone two or three times during the party, you are more likely to remember his or her name. Your brain has taken a short-term memory - the introduction - and converted it into a long-term one. The molecular key to this activity is mTORC2 (mammalian target of rapamycin complex 2), according to researchers at Baylor College of Medicine in an article that appeared online in the journal Nature Neuroscience.

"Memory consolidation is a fundamental process," said Dr. Mauro Costa-Mattioli, assistant professor of neuroscience at BCM and corresponding author of the report. "Memories are at the center of our identity. They allow us to remember people, places and events for a long time, even a lifetime. Understanding the precise mechanism by which memories are stored in the brain will lead to the development of new treatments for conditions associated with memory loss".

Actin fibers

For the last five decades, neuroscientists have known that making long-lasting memories is dependent on the ability of brain cells (neurons) to synthesize new proteins. In their studies, Costa-Mattioli and his colleagues found a new mechanism by which memories are stored in the brain. The newly discovered mTORC2 regulates memory formation by modulating actin fibers, an important component of the architectural structure of the neuron.

"These actin fibers allow long-lasting changes in synaptic strength and ultimately long-term memories," said Wei Huang, a BCM graduate student and first author in the study.

Using genetically-engineered mice, the researchers found that turning off mTORC2 in the hippocampus (a crucial region required for memory formation) and surrounding areas allowed the animals to have a normal short-term memory, but prevented them from forming long-term memories. Similar to human patients with injury in the hippocampus, these mutant mice were no longer able to form new long-lasting memories.

According to Costa-Mattioli’s findings, mTORC2’s role is evolutionarily conserved and likely relevant to humans. Like mTORC2-deficient mice, fruit flies lacking TORC2 show defective long-term memory storage.

"Given that flies and mice last shared a common ancestor 500 million years ago, it is quite remarkable and telling that the function of mTORC2 in the regulation of memory is indeed maintained," said Dr. Gregg Roman, director of the Biology of Behavior Institute at the University of Houston, who contributed to the fly experiments.

Form long-term memories

The Holy Grail of memory neuroscience and to a certain extent, of industry efforts to produce a “smart drug,” has been the identification of molecules that promote the formation of long-term memory, said Costa-Mattioli. “We therefore wondered whether by turning on mTORC2 or even actin polymerization itself, we could form long-term memories more easily,” said Dr. Ping Jun Zhu, assistant professor of neuroscience at BCM, co-first author and senior scientist in Costa-Mattioli’s lab.

The team has identified a small molecule (a drug) that by activating mTORC2 and consequently actin polymerization enhances not only the synaptic strength between nerve cells but also long-term memory formation. In addition, the authors found that by directly promoting actin polymerization, with a second drug, long-term memory is generated more easily.

Costa-Mattioli’s team has identified two memory-enhancing drugs, but can they enhance memory in people? It is perhaps too early to say.

Huang said, “mTORC2, as far as we know, is really a new potential target for therapeutic treatments of human disorders. In the next few years, I predict we will see a lot of studies focusing on mTORC2 as a target.”

Memory cocktail

Costa-Mattioli’s short-term goals are to identify human cognitive disorders in which mTORC2 activity is dysfunctional and to see whether its restoration can return to normal impaired memory function in aging or even Alzheimer’s disease. But a small molecule alone might not do the job. Similar to the treatments for HIV or cancer, he believes that a combination of small molecules improving different aspects of memory formation will be required to efficiently treat cognitive disorders.

"We should start thinking about an efficient ‘memory cocktail’ rather than a single ‘memory pill.’ One molecule alone might not be enough. We may be years away from a decisive treatment, but I believe we are definitely on the right path," he said.

Others who took part in this work include Hongyi Zhou, Loredana Stoica and Mauricio Galiano, all of BCM, Krešimir Krnjević of McGill University in Montreal, Canada; and Shixing Zhang of the University of Houston.

(Image: Shutterstock)

Filed under memory consolidation memory formation memory loss brain cells hippocampus neuroscience science

82 notes

The Role of Medial Prefrontal Cortex in Memory and Decision Making
Some have claimed that the medial prefrontal cortex (mPFC) mediates decision making. Others suggest mPFC is selectively involved in the retrieval of remote long-term memory. Yet others suggests mPFC supports memory and consolidation on time scales ranging from seconds to days. How can all these roles be reconciled? We propose that the function of the mPFC is to learn associations between context, locations, events, and corresponding adaptive responses, particularly emotional responses. Thus, the ubiquitous involvement of mPFC in both memory and decision making may be due to the fact that almost all such tasks entail the ability to recall the best action or emotional response to specific events in a particular place and time. An interaction between multiple memory systems may explain the changing importance of mPFC to different types of memories over time. In particular, mPFC likely relies on the hippocampus to support rapid learning and memory consolidation.

The Role of Medial Prefrontal Cortex in Memory and Decision Making

Some have claimed that the medial prefrontal cortex (mPFC) mediates decision making. Others suggest mPFC is selectively involved in the retrieval of remote long-term memory. Yet others suggests mPFC supports memory and consolidation on time scales ranging from seconds to days. How can all these roles be reconciled? We propose that the function of the mPFC is to learn associations between context, locations, events, and corresponding adaptive responses, particularly emotional responses. Thus, the ubiquitous involvement of mPFC in both memory and decision making may be due to the fact that almost all such tasks entail the ability to recall the best action or emotional response to specific events in a particular place and time. An interaction between multiple memory systems may explain the changing importance of mPFC to different types of memories over time. In particular, mPFC likely relies on the hippocampus to support rapid learning and memory consolidation.

Filed under mPFC prefrontal cortex decision making memory memory consolidation learning neuroscience science

134 notes

Brief exercise immediately enhances memory

A short burst of moderate exercise enhances the consolidation of memories in both healthy older adults and those with mild cognitive impairment, scientists with UC Irvine’s Center for the Neurobiology of Learning & Memory have discovered.

Most research has focused on the benefits of a long-term exercise program on overall health and cognitive function with age. But the UCI work is the first to examine the immediate effects of a brief bout of exercise on memory.

In their study, post-doctoral researcher Sabrina Segal and neurobiologists Carl Cotman and Lawrence Cahill had people 50 to 85 years old with and without memory deficits view pleasant images – such as photos of nature and animals – and then exercise on a stationary bicycle for six minutes at 70 percent of their maximum capacity immediately afterward.

One hour later, the participants were given a surprise recall test on the previously viewed images. Results showed a striking enhancement of memory by exercise in both the healthy and cognitively impaired adults, compared with subjects who did not ride the bike.

“We found that a single, short instance of moderately intense exercise particularly improved memory in individuals with memory deficits,” Segal said. “Because of its implications and the need to better understand the mechanism by which exercise may enhance memory, we’re following up this study with an investigation of potential underlying biological factors.”

She believes the improved memory may be related to the exercise-induced release of norepinephrine, a chemical messenger in the brain known to play a strong role in memory modulation. This hypothesis is based on previous work demonstrating that increasing norepinephrine through pharmacological manipulation sharpens memory and that blocking norepinephrine impairs memory.

In the more recent research, Segal and her colleagues discovered that levels of salivary alpha amylase, a biomarker that reflects norepinephrine activity in the brain, significantly increased in participants after exercise. This correlation was especially strong in people with memory impairment.

“The current findings offer a natural and relatively safe alternative to pharmacological interventions for memory enhancement in healthy older individuals as well as those who suffer from cognitive deficits,” Segal noted. “With a growing population of the aged, the need for improvement of quality of life and prevention of mental decline is more important than ever before.”

Study results appear in the November issue (Volume 32, Number 4) of the Journal of Alzheimer’s Disease.

(Source: news.uci.edu)

Filed under memory memory consolidation cognitive function norepinephrine neuroscience psychology science

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