Neuroscience

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Posts tagged memory

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Memory in silent neurons
When we learn, we associate a sensory experience either with other stimuli or with a certain type of behaviour. The neurons in the cerebral cortex that transmit the information modify the synaptic connections that they have with the other neurons. According to a generally-accepted model of synaptic plasticity, a neuron that communicates with others of the same kind emits an electrical impulse as well as activating its synapses transiently. This electrical pulse, combined with the signal received from other neurons, acts to stimulate the synapses. How is it that some neurons are caught up in the communication interplay even when they are barely connected? This is the crucial chicken-or-egg puzzle of synaptic plasticity that a team led by Anthony Holtmaat, professor in the Department of Basic Neurosciences in the Faculty of Medicine at UNIGE, is aiming to solve. The results of their research into memory in silent neurons can be found in the latest edition of Nature.
Learning and memory are governed by a mechanism of sustainable synaptic strengthening. When we embark on a learning experience, our brain associates a sensory experience either with other stimuli or with a certain form of behaviour. The neurons in the cerebral cortex responsible for ensuring the transmission of the relevant information, then modify the synaptic connections that they have with other neurons. This is the very arrangement that subsequently enables the brain to optimise the way information is processed when it is met again, as well as predicting its consequences.
Neuroscientists typically induce electrical pulses in the neurons artificially in order to perform research on synaptic mechanisms.
The neuroscientists from UNIGE, however, chose a different approach in their attempt to discover what happens naturally in the neurons when they receive sensory stimuli. They observed the cerebral cortices of mice whose whiskers were repeatedly stimulated mechanically without an artificially-induced electrical pulse. The rodents use their whiskers as a sensor for navigating and interacting; they are, therefore, a key element for perception in mice.
An extremely low signal is enough 
By observing these natural stimuli, professor Holtmaat’s team was able to demonstrate that sensory stimulus alone can generate long-term synaptic strengthening without the neuron discharging either an induced or natural electrical pulse. As a result – and contrary to what was previously believed – the synapses will be strengthened even when the neurons involved in a stimulus remain silent.In addition, if the sensory stimulation lasts over time, the synapses become so strong that the neuron in turn is activated and becomes fully engaged in the neural network. Once activated, the neuron can then further strengthen the synapses in a forwards and backwards movement. These findings could solve the brain’s “What came first?” mystery, as they make it possible to examine all the synaptic pathways that contribute to memory, rather than focusing on whether it is the synapsis or the neuron that activates the other.
The entire brain is mobilised
A second discovery lay in store for the researchers. During the same experiment, they were also able to establish that the stimuli that were most effective in strengthening the synapses came from secondary, non-cortical brain regions rather than major cortical pathways (which convey actual sensory information). Accordingly, storing information would simply require the co-activation of several synaptic pathways in the neuron, even if the latter remains silent. These findings may also have important implications both for the way we understand learning mechanisms and for therapeutic possibilities, in particular for rehabilitation following a stroke or in neurodegenerative disorders. As professor Holtmaat explains: “It is possible that sensory stimulation, when combined with another activity (motor activity, for example), works better for strengthening synaptic connections”. The professor concludes: “In the context of therapy, you could combine two different stimuli as a way of enhancing the effectiveness.”

Memory in silent neurons

When we learn, we associate a sensory experience either with other stimuli or with a certain type of behaviour. The neurons in the cerebral cortex that transmit the information modify the synaptic connections that they have with the other neurons. According to a generally-accepted model of synaptic plasticity, a neuron that communicates with others of the same kind emits an electrical impulse as well as activating its synapses transiently. This electrical pulse, combined with the signal received from other neurons, acts to stimulate the synapses. How is it that some neurons are caught up in the communication interplay even when they are barely connected? This is the crucial chicken-or-egg puzzle of synaptic plasticity that a team led by Anthony Holtmaat, professor in the Department of Basic Neurosciences in the Faculty of Medicine at UNIGE, is aiming to solve. The results of their research into memory in silent neurons can be found in the latest edition of Nature.

Learning and memory are governed by a mechanism of sustainable synaptic strengthening. When we embark on a learning experience, our brain associates a sensory experience either with other stimuli or with a certain form of behaviour. The neurons in the cerebral cortex responsible for ensuring the transmission of the relevant information, then modify the synaptic connections that they have with other neurons. This is the very arrangement that subsequently enables the brain to optimise the way information is processed when it is met again, as well as predicting its consequences.

Neuroscientists typically induce electrical pulses in the neurons artificially in order to perform research on synaptic mechanisms.

The neuroscientists from UNIGE, however, chose a different approach in their attempt to discover what happens naturally in the neurons when they receive sensory stimuli. They observed the cerebral cortices of mice whose whiskers were repeatedly stimulated mechanically without an artificially-induced electrical pulse. The rodents use their whiskers as a sensor for navigating and interacting; they are, therefore, a key element for perception in mice.

An extremely low signal is enough

By observing these natural stimuli, professor Holtmaat’s team was able to demonstrate that sensory stimulus alone can generate long-term synaptic strengthening without the neuron discharging either an induced or natural electrical pulse. As a result – and contrary to what was previously believed – the synapses will be strengthened even when the neurons involved in a stimulus remain silent.In addition, if the sensory stimulation lasts over time, the synapses become so strong that the neuron in turn is activated and becomes fully engaged in the neural network. Once activated, the neuron can then further strengthen the synapses in a forwards and backwards movement. These findings could solve the brain’s “What came first?” mystery, as they make it possible to examine all the synaptic pathways that contribute to memory, rather than focusing on whether it is the synapsis or the neuron that activates the other.

The entire brain is mobilised

A second discovery lay in store for the researchers. During the same experiment, they were also able to establish that the stimuli that were most effective in strengthening the synapses came from secondary, non-cortical brain regions rather than major cortical pathways (which convey actual sensory information). Accordingly, storing information would simply require the co-activation of several synaptic pathways in the neuron, even if the latter remains silent. These findings may also have important implications both for the way we understand learning mechanisms and for therapeutic possibilities, in particular for rehabilitation following a stroke or in neurodegenerative disorders. As professor Holtmaat explains: “It is possible that sensory stimulation, when combined with another activity (motor activity, for example), works better for strengthening synaptic connections”. The professor concludes: “In the context of therapy, you could combine two different stimuli as a way of enhancing the effectiveness.”

Filed under cerebral cortex memory learning neurons LTP somatosensory cortex synapses neuroscience science

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Researchers publish first study of brain activation in MS using fNIRS
Using functional near infrared spectroscopy (fNIRS), Kessler Foundation researchers have shown differential brain activation patterns between people with multiple sclerosis (MS) and healthy controls. This is the first MS study in which brain activation was studied using fNIRS while participants performed a cognitive task. The article, “Neuroimaging and cognition using functional near infrared spectroscopy (fNIRS) in multiple sclerosis,” was published online on June 11 by Brain Imaging and Behavior. Authors are Jelena Stojanovic-Radic, PhD, Glenn Wylie, DPhil, Gerald Voelbel, PhD, Nancy Chiaravalloti, PhD, and John DeLuca, PhD.
Researchers compared 13 individuals with MS with 12 controls for their performance on a working memory task with four levels of difficulty. Most such studies have employed functional magnetic resonance imaging (fMRI); fNIRS has been used infrequently in clinical populations, and has not been applied previously to neuroimaging research in MS.  Studies comparing fMRI findings with those of fNIRS, however, show broad agreement in terms of activation patterns.
Results showed differences in activation between the groups that were dependent on task load. The MS group had an increase in activation at low task difficulty and a decrease in activation at high task difficulty. Conversely, in the control group, activation decreased with low task difficulty and increased with high task difficulty. Performance accuracy was lower in the MS group for low task load; there were no differences between the groups at the higher task loads.  
“The data we obtained via fNIRS are consistent with fMRI data for clinical populations. We demonstrated that fNIRS is capable of detecting neuronal activation with a reasonable degree of detail,” noted Glenn Wylie, DPhil, associate director of Neuroscience and the Neuroimaging Center at Kessler Foundation. “We attribute the differences in brain activation patterns to the effort expended during the working memory task rather than to differences in speed of processing,” he added. “Because fNIRS is more portable and easier to use that fMRI, it may offer advantages in monitoring cognitive interventions that require frequent scans.”
In addition to working memory, future research in clinical populations should focus on processing speed and episodic memory, cognitive functions that are also affected in MS.
(Image credit)

Researchers publish first study of brain activation in MS using fNIRS

Using functional near infrared spectroscopy (fNIRS), Kessler Foundation researchers have shown differential brain activation patterns between people with multiple sclerosis (MS) and healthy controls. This is the first MS study in which brain activation was studied using fNIRS while participants performed a cognitive task. The article, “Neuroimaging and cognition using functional near infrared spectroscopy (fNIRS) in multiple sclerosis,” was published online on June 11 by Brain Imaging and Behavior. Authors are Jelena Stojanovic-Radic, PhD, Glenn Wylie, DPhil, Gerald Voelbel, PhD, Nancy Chiaravalloti, PhD, and John DeLuca, PhD.

Researchers compared 13 individuals with MS with 12 controls for their performance on a working memory task with four levels of difficulty. Most such studies have employed functional magnetic resonance imaging (fMRI); fNIRS has been used infrequently in clinical populations, and has not been applied previously to neuroimaging research in MS.  Studies comparing fMRI findings with those of fNIRS, however, show broad agreement in terms of activation patterns.

Results showed differences in activation between the groups that were dependent on task load. The MS group had an increase in activation at low task difficulty and a decrease in activation at high task difficulty. Conversely, in the control group, activation decreased with low task difficulty and increased with high task difficulty. Performance accuracy was lower in the MS group for low task load; there were no differences between the groups at the higher task loads.  

“The data we obtained via fNIRS are consistent with fMRI data for clinical populations. We demonstrated that fNIRS is capable of detecting neuronal activation with a reasonable degree of detail,” noted Glenn Wylie, DPhil, associate director of Neuroscience and the Neuroimaging Center at Kessler Foundation. “We attribute the differences in brain activation patterns to the effort expended during the working memory task rather than to differences in speed of processing,” he added. “Because fNIRS is more portable and easier to use that fMRI, it may offer advantages in monitoring cognitive interventions that require frequent scans.”

In addition to working memory, future research in clinical populations should focus on processing speed and episodic memory, cognitive functions that are also affected in MS.

(Image credit)

Filed under MS fNIRS neuroimaging brain activity cognition memory neuroscience science

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Neuroscientists watch imagination happening in the brain
“You may say I’m a dreamer, but I’m not the only one,” sang John Lennon in his 1971 song Imagine.
And thanks to the dreams of a BYU student, we now know more about where and how imagination happens in our brains.
Stefania Ashby and her faculty mentor devised experiments using MRI technology that would help them distinguish pure imagination from related processes like remembering.
“I was thinking a lot about planning for my own future and imagining myself in the future, and I started wondering how memory and imagination work together,” Ashby said. “I wondered if they were separate or if imagination is just taking past memories and combining them in different ways to form something I’ve never experienced before.”
There’s a bit of scientific debate over whether memory and imagination truly are distinct processes. So Ashby and her faculty mentor devised MRI experiments to put it to the test.
They asked study participants to provide 60 personal photographs for the “remember” section of the experiment. Participants also filled out a questionnaire beforehand to determine which scenarios would be unfamiliar to them and thus a better fit for the “imagine” section.
The researchers then showed people their own photographs during an MRI session to elicit brain activity that is strictly memory-based. A statistical analysis revealed distinctive patterns for memory and imagination.
“We were able to see the distinctions even in those small regions of the hippocampus,” Ashby said. “It’s really neat that we can see the difference between those two tasks in that small of a brain region.”
Ashby co-authored the study with BYU psychology and neuroscience professor Brock Kirwan for the journal Cognitive Neuroscience. Kirwan studies memory at Brigham Young University, and Ashby is one of many students that he has mentored.
“Stefania came in really excited about this project, she pitched it to me, and basically sold it to me right there,” Kirwan said. “It was really cool because it gave me a chance to become more immersed and really broaden my horizons.”
Stefania graduated in 2011 and is currently working as a research associate at UC Davis, where she uses neuroimaging to study individuals at risk of psychotic disorders such as schizophrenia. Her plan is to earn a Ph.D. in neuroscience and continue researching.

Neuroscientists watch imagination happening in the brain

“You may say I’m a dreamer, but I’m not the only one,” sang John Lennon in his 1971 song Imagine.

And thanks to the dreams of a BYU student, we now know more about where and how imagination happens in our brains.

Stefania Ashby and her faculty mentor devised experiments using MRI technology that would help them distinguish pure imagination from related processes like remembering.

“I was thinking a lot about planning for my own future and imagining myself in the future, and I started wondering how memory and imagination work together,” Ashby said. “I wondered if they were separate or if imagination is just taking past memories and combining them in different ways to form something I’ve never experienced before.”

There’s a bit of scientific debate over whether memory and imagination truly are distinct processes. So Ashby and her faculty mentor devised MRI experiments to put it to the test.

They asked study participants to provide 60 personal photographs for the “remember” section of the experiment. Participants also filled out a questionnaire beforehand to determine which scenarios would be unfamiliar to them and thus a better fit for the “imagine” section.

The researchers then showed people their own photographs during an MRI session to elicit brain activity that is strictly memory-based. A statistical analysis revealed distinctive patterns for memory and imagination.

“We were able to see the distinctions even in those small regions of the hippocampus,” Ashby said. “It’s really neat that we can see the difference between those two tasks in that small of a brain region.”

Ashby co-authored the study with BYU psychology and neuroscience professor Brock Kirwan for the journal Cognitive Neuroscience. Kirwan studies memory at Brigham Young University, and Ashby is one of many students that he has mentored.

“Stefania came in really excited about this project, she pitched it to me, and basically sold it to me right there,” Kirwan said. “It was really cool because it gave me a chance to become more immersed and really broaden my horizons.”

Stefania graduated in 2011 and is currently working as a research associate at UC Davis, where she uses neuroimaging to study individuals at risk of psychotic disorders such as schizophrenia. Her plan is to earn a Ph.D. in neuroscience and continue researching.

Filed under imagination memory hippocampus neuroimaging brain activity neuroscience science

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Electric Current to Brain Boosts Memory
Stimulating a particular region in the brain via non-invasive delivery of electrical current using magnetic pulses, called Transcranial Magnetic Stimulation, improves memory, reports a new Northwestern Medicine® study.
The discovery opens a new field of possibilities for treating memory impairments caused by conditions such as stroke, early-stage Alzheimer’s disease, traumatic brain injury, cardiac arrest and the memory problems that occur in healthy aging.
“We show for the first time that you can specifically change memory functions of the brain in adults without surgery or drugs, which have not proven effective,” said senior author Joel Voss, assistant professor of medical social sciences at Northwestern University Feinberg School of Medicine. “This noninvasive stimulation improves the ability to learn new things. It has tremendous potential for treating memory disorders.”
The study was published August 29 in Science.
The study also is the first to demonstrate that remembering events requires a collection of many brain regions to work in concert with a key memory structure called the hippocampus – similar to a symphony orchestra. The electrical stimulation is like giving the brain regions a more talented conductor so they play in closer synchrony. 
“It’s like we replaced their normal conductor with Muti,” Voss said, referring to Riccardo Muti, the music director of the renowned Chicago Symphony Orchestra. “The brain regions played together better after the stimulation.”
The approach also has potential for treating mental disorders such as schizophrenia in which these brain regions and the hippocampus are out of sync with each other, affecting memory and cognition.    
TMS Boosts Memory 
The Northwestern study is the first to show TMS improves memory long after treatment. In the past, TMS has been used in a limited way to temporarily change brain function to improve performance during a test, for example, making someone push a button slightly faster while the brain is being stimulated. The study shows that TMS can be used to improve memory for events at least 24 hours after the stimulation is given.
Finding the Sweet Spot
It isn’t possible to directly stimulate the hippocampus with TMS because it’s too deep in the brain for the magnetic fields to penetrate. So, using an MRI scan, Voss and colleagues identified a superficial brain region a mere centimeter from the surface of the skull with high connectivity to the hippocampus. He wanted to see if directing the stimulation to this spot would in turn stimulate the hippocampus. It did.
“I was astonished to see that it worked so specifically,” Voss said.
When TMS was used to stimulate this spot, regions in the brain involved with the hippocampus became more synchronized with each other, as indicated by data taken while subjects were inside an MRI machine, which records the blood flow in the brain as an indirect measure of neuronal activity.
The more those regions worked together due to the stimulation, the better people were able to learn new information.
How the Study Worked
Scientists recruited 16 healthy adults ages 21 to 40. Each had a detailed anatomical image taken of his or her brain as well as 10 minutes of recording brain activity while lying quietly inside an MRI scanner. Doing this allowed the researchers to identify each person’s network of brain structures that are involved in memory and well connected to the hippocampus. The structures are slightly different in each person and may vary in location by as much as a few centimeters.
“To properly target the stimulation, we had to identify the structures in each person’s brain space because everyone’s brain is different,” Voss said. 
Each participant then underwent a memory test, consisting of a set of arbitrary associations between faces and words that they were asked to learn and remember. After establishing their baseline ability to perform on this memory task, participants received brain stimulation 20 minutes a day for five consecutive days. 
During the week they also received additional MRI scans and tests of their ability to remember new sets of arbitrary word and face parings to see how their memory changed as a result of the stimulation. Then, at least 24 hours after the final stimulation, they were tested again.
At least one week later, the same experiment was repeated but with a fake placebo stimulation. The order of real stimulation and placebo portions of the study was reversed for half of the participants, and they weren’t told which was which.
Both groups performed better on memory tests as a result of the brain stimulation. It took three days of stimulation before they improved.
“They remembered more face-word pairings after the stimulation than before, which means their learning ability improved,” Voss said. “That didn’t happen for the placebo condition or in another control experiment with additional subjects.”
In addition, the MRI showed the stimulation caused the brain regions to become more synchronized with each other and the hippocampus. The greater the improvement in the synchronicity or connectivity between specific parts of the network, the better the performance on the memory test. “The more certain brain regions worked together because of the stimulation, the more people were able to learn face-word pairings, “ Voss said.
Using TMS to stimulate memory has multiple advantages, noted first author Jane Wang, a postdoctoral fellow in Voss’s lab at Feinberg. “No medication could be as specific as TMS for these memory networks,” Wang said. “There are a lot of different targets and it’s not easy to come up with any one receptor that’s involved in memory.”
The Future 
“This opens up a whole new area for treatment studies where we will try to see if we can improve function in people who really need it,“ Voss said.
His current study was with people who had normal memory, in whom he wouldn’t expect to see a big improvement because their brains are already working effectively.
“But for a person with brain damage or a memory disorder, those networks are disrupted so even a small change could translate into gains in their function,” Voss said.
In an upcoming trial, Voss will study the electrical stimulation’s effect on people with early-stage memory loss.
Voss cautioned that years of research are needed to determine whether this approach is safe or effective for patients with Alzheimer’s disease or similar disorders of memory.

Electric Current to Brain Boosts Memory

Stimulating a particular region in the brain via non-invasive delivery of electrical current using magnetic pulses, called Transcranial Magnetic Stimulation, improves memory, reports a new Northwestern Medicine® study.

The discovery opens a new field of possibilities for treating memory impairments caused by conditions such as stroke, early-stage Alzheimer’s disease, traumatic brain injury, cardiac arrest and the memory problems that occur in healthy aging.

“We show for the first time that you can specifically change memory functions of the brain in adults without surgery or drugs, which have not proven effective,” said senior author Joel Voss, assistant professor of medical social sciences at Northwestern University Feinberg School of Medicine. “This noninvasive stimulation improves the ability to learn new things. It has tremendous potential for treating memory disorders.”

The study was published August 29 in Science.

The study also is the first to demonstrate that remembering events requires a collection of many brain regions to work in concert with a key memory structure called the hippocampus – similar to a symphony orchestra. The electrical stimulation is like giving the brain regions a more talented conductor so they play in closer synchrony. 

“It’s like we replaced their normal conductor with Muti,” Voss said, referring to Riccardo Muti, the music director of the renowned Chicago Symphony Orchestra. “The brain regions played together better after the stimulation.”

The approach also has potential for treating mental disorders such as schizophrenia in which these brain regions and the hippocampus are out of sync with each other, affecting memory and cognition.    

TMS Boosts Memory 

The Northwestern study is the first to show TMS improves memory long after treatment. In the past, TMS has been used in a limited way to temporarily change brain function to improve performance during a test, for example, making someone push a button slightly faster while the brain is being stimulated. The study shows that TMS can be used to improve memory for events at least 24 hours after the stimulation is given.

Finding the Sweet Spot

It isn’t possible to directly stimulate the hippocampus with TMS because it’s too deep in the brain for the magnetic fields to penetrate. So, using an MRI scan, Voss and colleagues identified a superficial brain region a mere centimeter from the surface of the skull with high connectivity to the hippocampus. He wanted to see if directing the stimulation to this spot would in turn stimulate the hippocampus. It did.

“I was astonished to see that it worked so specifically,” Voss said.

When TMS was used to stimulate this spot, regions in the brain involved with the hippocampus became more synchronized with each other, as indicated by data taken while subjects were inside an MRI machine, which records the blood flow in the brain as an indirect measure of neuronal activity.

The more those regions worked together due to the stimulation, the better people were able to learn new information.

How the Study Worked

Scientists recruited 16 healthy adults ages 21 to 40. Each had a detailed anatomical image taken of his or her brain as well as 10 minutes of recording brain activity while lying quietly inside an MRI scanner. Doing this allowed the researchers to identify each person’s network of brain structures that are involved in memory and well connected to the hippocampus. The structures are slightly different in each person and may vary in location by as much as a few centimeters.

“To properly target the stimulation, we had to identify the structures in each person’s brain space because everyone’s brain is different,” Voss said. 

Each participant then underwent a memory test, consisting of a set of arbitrary associations between faces and words that they were asked to learn and remember. After establishing their baseline ability to perform on this memory task, participants received brain stimulation 20 minutes a day for five consecutive days. 

During the week they also received additional MRI scans and tests of their ability to remember new sets of arbitrary word and face parings to see how their memory changed as a result of the stimulation. Then, at least 24 hours after the final stimulation, they were tested again.

At least one week later, the same experiment was repeated but with a fake placebo stimulation. The order of real stimulation and placebo portions of the study was reversed for half of the participants, and they weren’t told which was which.

Both groups performed better on memory tests as a result of the brain stimulation. It took three days of stimulation before they improved.

“They remembered more face-word pairings after the stimulation than before, which means their learning ability improved,” Voss said. “That didn’t happen for the placebo condition or in another control experiment with additional subjects.”

In addition, the MRI showed the stimulation caused the brain regions to become more synchronized with each other and the hippocampus. The greater the improvement in the synchronicity or connectivity between specific parts of the network, the better the performance on the memory test. “The more certain brain regions worked together because of the stimulation, the more people were able to learn face-word pairings, “ Voss said.

Using TMS to stimulate memory has multiple advantages, noted first author Jane Wang, a postdoctoral fellow in Voss’s lab at Feinberg. “No medication could be as specific as TMS for these memory networks,” Wang said. “There are a lot of different targets and it’s not easy to come up with any one receptor that’s involved in memory.”

The Future 

“This opens up a whole new area for treatment studies where we will try to see if we can improve function in people who really need it,“ Voss said.

His current study was with people who had normal memory, in whom he wouldn’t expect to see a big improvement because their brains are already working effectively.

“But for a person with brain damage or a memory disorder, those networks are disrupted so even a small change could translate into gains in their function,” Voss said.

In an upcoming trial, Voss will study the electrical stimulation’s effect on people with early-stage memory loss.

Voss cautioned that years of research are needed to determine whether this approach is safe or effective for patients with Alzheimer’s disease or similar disorders of memory.

Filed under memory transcranial magnetic stimulation hippocampus brain stimulation brain activity neuroscience science

203 notes

Xenon Exposure Shown to Erase Traumatic Memories

McLean Hospital researchers are reporting that xenon gas, used in humans for anesthesia and diagnostic imaging, has the potential to be a treatment for post-traumatic stress disorder (PTSD) and other memory-related disorders.

“In our study, we found that xenon gas has the capability of reducing memories of traumatic events,” said Edward G. Meloni, PhD, assistant psychologist at McLean Hospital and an assistant professor of Psychiatry at Harvard Medical School. “It’s an exciting breakthrough, as this has the potential to be a new treatment for individuals suffering from PTSD.”

In the study, published in the current issue of PLOS ONE, Meloni, and Marc J. Kaufman, PhD, director of the McLean Hospital Translational Imaging Laboratory, examined whether a low concentration of xenon gas could interfere with a process called reconsolidation – a state in which reactivated memories become susceptible to modification. “We know from previous research that each time an emotional memory is recalled, the brain actually restores it as if it were a new memory. With this knowledge, we decided to see whether we could alter the process by introducing xenon gas immediately after a fear memory was reactivated,” explained Meloni.

The investigators used an animal model of PTSD called fear-conditioning to train rats to be afraid of environmental cues that were paired with brief footshocks. Reactivating the fearful memory was done by exposing the rats to those same cues and measuring their freezing response as a readout of fear. “We found that a single exposure to the gas, which is known to block NMDA receptors involved in memory formation in the brain, dramatically and persistently reduced fear responses for up to 2 weeks.  It was as though the animals no longer remembered to be afraid of those cues”, said Dr. Meloni.

Meloni points out that the inherent properties of a gas such as xenon make it especially attractive for targeting dynamic processes such as memory reconsolidation. “Unlike other drugs or medications that may also block NMDA receptors involved in memory, xenon gets in and out of the brain very quickly. This suggests that xenon could be given at the exact time the memory is reactivated, and for a limited amount of time, which may be key features for any potential therapy used in humans.”

“The fact that we were able to inhibit remembering of a traumatic memory with xenon is very promising because it is currently used in humans for other purposes, and thus it could be repurposed to treat PTSD,” added Kaufman.

For these investigators, several questions remain to be addressed with further testing. “From here we want to explore whether lower xenon doses or shorter exposure times would also block memory reconsolidation and the expression of fear. We’d also like to know if xenon is as effective at reducing traumatic memories from past events, so-called remote memories, versus the newly formed ones we tested in our study”.

Meloni and Kaufman indicate that future studies are planned to test if the effects of xenon in rats seen in their study translate to humans. Given that intrusive re-experiencing of traumatic memories – including flashbacks, nightmares, and distress and physiological reactions induced when confronted with trauma reminders – is a hallmark symptom for many who suffer from PTSD, a treatment that alleviates the impact of those painful memories could provide welcome relief.

(Source: mcleanhospital.org)

Filed under xenon PTSD memory reconsolidation fear conditioning memory NMDA receptors neuroscience science

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(Image caption: This image depicts the injection sites and the expression of the viral constructs in the two areas of the brain studied: the Dentate Gyrus of the hippocampus (middle) and the Basolateral Amygdala (bottom corners). Image courtesy of the researchers)
Neuroscientists reverse memories’ emotional associations
Most memories have some kind of emotion associated with them: Recalling the week you just spent at the beach probably makes you feel happy, while reflecting on being bullied provokes more negative feelings.
A new study from MIT neuroscientists reveals the brain circuit that controls how memories become linked with positive or negative emotions. Furthermore, the researchers found that they could reverse the emotional association of specific memories by manipulating brain cells with optogenetics — a technique that uses light to control neuron activity.
The findings, described in the Aug. 27 issue of Nature, demonstrated that a neuronal circuit connecting the hippocampus and the amygdala plays a critical role in associating emotion with memory. This circuit could offer a target for new drugs to help treat conditions such as post-traumatic stress disorder, the researchers say.
“In the future, one may be able to develop methods that help people to remember positive memories more strongly than negative ones,” says Susumu Tonegawa, the Picower Professor of Biology and Neuroscience, director of the RIKEN-MIT Center for Neural Circuit Genetics at MIT’s Picower Institute for Learning and Memory, and senior author of the paper.
The paper’s lead authors are Roger Redondo, a Howard Hughes Medical Institute postdoc at MIT, and Joshua Kim, a graduate student in MIT’s Department of Biology.
Shifting memories
Memories are made of many elements, which are stored in different parts of the brain. A memory’s context, including information about the location where the event took place, is stored in cells of the hippocampus, while emotions linked to that memory are found in the amygdala.
Previous research has shown that many aspects of memory, including emotional associations, are malleable. Psychotherapists have taken advantage of this to help patients suffering from depression and post-traumatic stress disorder, but the neural circuitry underlying such malleability is not known.
In this study, the researchers set out to explore that malleability with an experimental technique they recently devised that allows them to tag neurons that encode a specific memory, or engram. To achieve this, they label hippocampal cells that are turned on during memory formation with a light-sensitive protein called channelrhodopsin. From that point on, any time those cells are activated with light, the mice recall the memory encoded by that group of cells.
Last year, Tonegawa’s lab used this technique to implant, or “incept,” false memories in mice by reactivating engrams while the mice were undergoing a different experience. In the new study, the researchers wanted to investigate how the context of a memory becomes linked to a particular emotion. First, they used their engram-labeling protocol to tag neurons associated with either a rewarding experience (for male mice, socializing with a female mouse) or an unpleasant experience (a mild electrical shock). In this first set of experiments, the researchers labeled memory cells in a part of the hippocampus called the dentate gyrus.
Two days later, the mice were placed into a large rectangular arena. For three minutes, the researchers recorded which half of the arena the mice naturally preferred. Then, for mice that had received the fear conditioning, the researchers stimulated the labeled cells in the dentate gyrus with light whenever the mice went into the preferred side. The mice soon began avoiding that area, showing that the reactivation of the fear memory had been successful.
The reward memory could also be reactivated: For mice that were reward-conditioned, the researchers stimulated them with light whenever they went into the less-preferred side, and they soon began to spend more time there, recalling the pleasant memory.
A couple of days later, the researchers tried to reverse the mice’s emotional responses. For male mice that had originally received the fear conditioning, they activated the memory cells involved in the fear memory with light for 12 minutes while the mice spent time with female mice. For mice that had initially received the reward conditioning, memory cells were activated while they received mild electric shocks.
Next, the researchers again put the mice in the large two-zone arena. This time, the mice that had originally been conditioned with fear and had avoided the side of the chamber where their hippocampal cells were activated by the laser now began to spend more time in that side when their hippocampal cells were activated, showing that a pleasant association had replaced the fearful one. This reversal also took place in mice that went from reward to fear conditioning.
Altered connections
The researchers then performed the same set of experiments but labeled memory cells in the basolateral amygdala, a region involved in processing emotions. This time, they could not induce a switch by reactivating those cells — the mice continued to behave as they had been conditioned when the memory cells were first labeled.
This suggests that emotional associations, also called valences, are encoded somewhere in the neural circuitry that connects the dentate gyrus to the amygdala, the researchers say. A fearful experience strengthens the connections between the hippocampal engram and fear-encoding cells in the amygdala, but that connection can be weakened later on as new connections are formed between the hippocampus and amygdala cells that encode positive associations.
“That plasticity of the connection between the hippocampus and the amygdala plays a crucial role in the switching of the valence of the memory,” Tonegawa says.
These results indicate that while dentate gyrus cells are neutral with respect to emotion, individual amygdala cells are precommitted to encode fear or reward memory. The researchers are now trying to discover molecular signatures of these two types of amygdala cells. They are also investigating whether reactivating pleasant memories has any effect on depression, in hopes of identifying new targets for drugs to treat depression and post-traumatic stress disorder.
David Anderson, a professor of biology at the California Institute of Technology, says the study makes an important contribution to neuroscientists’ fundamental understanding of the brain and also has potential implications for treating mental illness.
“This is a tour de force of modern molecular-biology-based methods for analyzing processes, such as learning and memory, at the neural-circuitry level. It’s one of the most sophisticated studies of this type that I’ve seen,” he says.

(Image caption: This image depicts the injection sites and the expression of the viral constructs in the two areas of the brain studied: the Dentate Gyrus of the hippocampus (middle) and the Basolateral Amygdala (bottom corners). Image courtesy of the researchers)

Neuroscientists reverse memories’ emotional associations

Most memories have some kind of emotion associated with them: Recalling the week you just spent at the beach probably makes you feel happy, while reflecting on being bullied provokes more negative feelings.

A new study from MIT neuroscientists reveals the brain circuit that controls how memories become linked with positive or negative emotions. Furthermore, the researchers found that they could reverse the emotional association of specific memories by manipulating brain cells with optogenetics — a technique that uses light to control neuron activity.

The findings, described in the Aug. 27 issue of Nature, demonstrated that a neuronal circuit connecting the hippocampus and the amygdala plays a critical role in associating emotion with memory. This circuit could offer a target for new drugs to help treat conditions such as post-traumatic stress disorder, the researchers say.

“In the future, one may be able to develop methods that help people to remember positive memories more strongly than negative ones,” says Susumu Tonegawa, the Picower Professor of Biology and Neuroscience, director of the RIKEN-MIT Center for Neural Circuit Genetics at MIT’s Picower Institute for Learning and Memory, and senior author of the paper.

The paper’s lead authors are Roger Redondo, a Howard Hughes Medical Institute postdoc at MIT, and Joshua Kim, a graduate student in MIT’s Department of Biology.

Shifting memories

Memories are made of many elements, which are stored in different parts of the brain. A memory’s context, including information about the location where the event took place, is stored in cells of the hippocampus, while emotions linked to that memory are found in the amygdala.

Previous research has shown that many aspects of memory, including emotional associations, are malleable. Psychotherapists have taken advantage of this to help patients suffering from depression and post-traumatic stress disorder, but the neural circuitry underlying such malleability is not known.

In this study, the researchers set out to explore that malleability with an experimental technique they recently devised that allows them to tag neurons that encode a specific memory, or engram. To achieve this, they label hippocampal cells that are turned on during memory formation with a light-sensitive protein called channelrhodopsin. From that point on, any time those cells are activated with light, the mice recall the memory encoded by that group of cells.

Last year, Tonegawa’s lab used this technique to implant, or “incept,” false memories in mice by reactivating engrams while the mice were undergoing a different experience. In the new study, the researchers wanted to investigate how the context of a memory becomes linked to a particular emotion. First, they used their engram-labeling protocol to tag neurons associated with either a rewarding experience (for male mice, socializing with a female mouse) or an unpleasant experience (a mild electrical shock). In this first set of experiments, the researchers labeled memory cells in a part of the hippocampus called the dentate gyrus.

Two days later, the mice were placed into a large rectangular arena. For three minutes, the researchers recorded which half of the arena the mice naturally preferred. Then, for mice that had received the fear conditioning, the researchers stimulated the labeled cells in the dentate gyrus with light whenever the mice went into the preferred side. The mice soon began avoiding that area, showing that the reactivation of the fear memory had been successful.

The reward memory could also be reactivated: For mice that were reward-conditioned, the researchers stimulated them with light whenever they went into the less-preferred side, and they soon began to spend more time there, recalling the pleasant memory.

A couple of days later, the researchers tried to reverse the mice’s emotional responses. For male mice that had originally received the fear conditioning, they activated the memory cells involved in the fear memory with light for 12 minutes while the mice spent time with female mice. For mice that had initially received the reward conditioning, memory cells were activated while they received mild electric shocks.

Next, the researchers again put the mice in the large two-zone arena. This time, the mice that had originally been conditioned with fear and had avoided the side of the chamber where their hippocampal cells were activated by the laser now began to spend more time in that side when their hippocampal cells were activated, showing that a pleasant association had replaced the fearful one. This reversal also took place in mice that went from reward to fear conditioning.

Altered connections

The researchers then performed the same set of experiments but labeled memory cells in the basolateral amygdala, a region involved in processing emotions. This time, they could not induce a switch by reactivating those cells — the mice continued to behave as they had been conditioned when the memory cells were first labeled.

This suggests that emotional associations, also called valences, are encoded somewhere in the neural circuitry that connects the dentate gyrus to the amygdala, the researchers say. A fearful experience strengthens the connections between the hippocampal engram and fear-encoding cells in the amygdala, but that connection can be weakened later on as new connections are formed between the hippocampus and amygdala cells that encode positive associations.

“That plasticity of the connection between the hippocampus and the amygdala plays a crucial role in the switching of the valence of the memory,” Tonegawa says.

These results indicate that while dentate gyrus cells are neutral with respect to emotion, individual amygdala cells are precommitted to encode fear or reward memory. The researchers are now trying to discover molecular signatures of these two types of amygdala cells. They are also investigating whether reactivating pleasant memories has any effect on depression, in hopes of identifying new targets for drugs to treat depression and post-traumatic stress disorder.

David Anderson, a professor of biology at the California Institute of Technology, says the study makes an important contribution to neuroscientists’ fundamental understanding of the brain and also has potential implications for treating mental illness.

“This is a tour de force of modern molecular-biology-based methods for analyzing processes, such as learning and memory, at the neural-circuitry level. It’s one of the most sophisticated studies of this type that I’ve seen,” he says.

Filed under optogenetics hippocampus memory emotions amygdala dentate gyrus neuroscience science

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How the Brain Makes Sense of Spaces, Large and Small







When an animal encounters a new environment, the neurons in its brain that are responsible for mapping out the space are ready for anything. So says a new study in which scientists at the Howard Hughes Medical Institute’s Janelia Research Campus examined neuronal activity in rats as they explored an unusually large maze for the first time.
The researchers found that neurons in the brain’s hippocampus, where information about people, places, and events is stored, each contribute to an animal’s mental map at their own rate. Some neurons begin to associate themselves with the new space immediately, while others hold back, contributing only if the space expands beyond a size that can be represented by the first-line neurons. Similar mechanisms may be at play as the human brain records a new experience, says Janelia group leader Albert Lee, who led the study. Lee, graduate student Dylan Rich, and Hua Peng-Liaw, a technician in Lee’s lab, published their findings in the August 15, 2014, issue of the journal Science.
“The hippocampus has to represent arbitrary things,” Lee says. “When a new experience begins, we don’t know how long it’s going to last, and the brain has to form a new representation on the fly. This mechanism means that the hippocampus doesn’t have to adjust its representation if an environment is larger than predicted, or if an experience goes on longer than expected.”
As an animal explores a new environment, cells in its hippocampus fire to mark new places that it encounters. The cells, called place cells, fire randomly, but become associated with the shapes, smells, and other sensory cues present in that location. In humans, analogous cells store memories of people, places, facts, and events.
In rodents, about a third of the cells in the region of the hippocampus devoted to spatial learning participate in mapping a typical laboratory-sized maze. Different mazes are represented by different but overlapping sets of neurons. The differences between those sets allow the brain to distinguish between memories of different environments.
But what happens when an animal finds itself in an environment larger than a five-meter laboratory maze? In the wild, rats can traverse territories as long as 50 meters. Lee wanted to know how the hippocampus kept track of environments that placed greater demands on its neurons.
If cells continued to mark off space at the rate that scientists had observed in more confined environments, the animal’s mental map would quickly lose its uniqueness. “If every cell is active in the representation of a single space, then you can’t use this mechanism to distinguish memories of different things,” Lee points out. 
So Lee and his team stocked up on supplies from the hardware store and built their own maze, far larger than any that had been used previously to track place cell activity. The 48-meter maze wouldn’t fit inside Lee’s lab, so Lee, Rich, and Liaw set it up in a large cage-cleaning room at Janelia.
The room was busy during the week, so the team did their experiments on weekends. For multiple weekends over the course of about two years, Janelia’s vivarium staff would clear the room for them, and then the team would reassemble the maze and set up video cameras and electrophysiology equipment. The team recorded the activity of individual cells in the hippocampus as rats explored the maze for the first time. They first introduced the animals to a small portion of the maze, then gradually increased the territory to which the rats had access, monitoring how the brain added new information to its spatial map.
When the scientists analyzed their data, they discovered that from the time the rats entered the maze, their brains were ready to represent an environment of any size. “Instead of the hippocampus having to adjust in time as the animal notices that the maze gets larger, it anticipates all different sizes of mazes from the beginning,” Lee says. “It does this by dividing up its population of neurons so that certain ones are ready to represent smaller mazes, others are ready to represent medium-size mazes, and others, large ones.”
All of the neurons acted independently, firing randomly to mark off places in the maze. But some neurons had a greater propensity to mark off space than others, Lee explains. Some neurons mark space quickly and become associated with many places in the maze, whereas others are less likely to fire. These, Lee says, are reserved for mapping larger spaces.
In small environments, a subset of the cells that are most likely to mark off space – those that have a chance to fire while the animal explores – form the map on their own. In larger mazes, all of the neurons with a high propensity to mark space are recruited to the mapping effort, meaning they cannot be used to distinguish the representation of one large maze from another. That’s when the neurons with a lower tendency to fire step in, randomly marking space in a distinct, identifying set.
“There’s always a set of neurons that is just at the edge, where they are equally likely to represent any given environment versus not, regardless of what its size is,” Lee says. “Those are the neurons the brain can actually use to distinguish which environment its in.”
The system means the brain never has to adjust its representation of an environment as it is being created, Lee says. “All neurons are marking space at their own preferred rate, so there doesn’t have to be a mechanism to say, ‘you should fire because this maze is large or this maze is small.’ The hippocampus is ready for anything at any moment.”
Cells in the human brain may record events in a similar way, marking off time as an event unfolds without knowing how long it will continue, Lee says.

How the Brain Makes Sense of Spaces, Large and Small

When an animal encounters a new environment, the neurons in its brain that are responsible for mapping out the space are ready for anything. So says a new study in which scientists at the Howard Hughes Medical Institute’s Janelia Research Campus examined neuronal activity in rats as they explored an unusually large maze for the first time.

The researchers found that neurons in the brain’s hippocampus, where information about people, places, and events is stored, each contribute to an animal’s mental map at their own rate. Some neurons begin to associate themselves with the new space immediately, while others hold back, contributing only if the space expands beyond a size that can be represented by the first-line neurons. Similar mechanisms may be at play as the human brain records a new experience, says Janelia group leader Albert Lee, who led the study. Lee, graduate student Dylan Rich, and Hua Peng-Liaw, a technician in Lee’s lab, published their findings in the August 15, 2014, issue of the journal Science.

“The hippocampus has to represent arbitrary things,” Lee says. “When a new experience begins, we don’t know how long it’s going to last, and the brain has to form a new representation on the fly. This mechanism means that the hippocampus doesn’t have to adjust its representation if an environment is larger than predicted, or if an experience goes on longer than expected.”

As an animal explores a new environment, cells in its hippocampus fire to mark new places that it encounters. The cells, called place cells, fire randomly, but become associated with the shapes, smells, and other sensory cues present in that location. In humans, analogous cells store memories of people, places, facts, and events.

In rodents, about a third of the cells in the region of the hippocampus devoted to spatial learning participate in mapping a typical laboratory-sized maze. Different mazes are represented by different but overlapping sets of neurons. The differences between those sets allow the brain to distinguish between memories of different environments.

But what happens when an animal finds itself in an environment larger than a five-meter laboratory maze? In the wild, rats can traverse territories as long as 50 meters. Lee wanted to know how the hippocampus kept track of environments that placed greater demands on its neurons.

If cells continued to mark off space at the rate that scientists had observed in more confined environments, the animal’s mental map would quickly lose its uniqueness. “If every cell is active in the representation of a single space, then you can’t use this mechanism to distinguish memories of different things,” Lee points out. 

So Lee and his team stocked up on supplies from the hardware store and built their own maze, far larger than any that had been used previously to track place cell activity. The 48-meter maze wouldn’t fit inside Lee’s lab, so Lee, Rich, and Liaw set it up in a large cage-cleaning room at Janelia.

The room was busy during the week, so the team did their experiments on weekends. For multiple weekends over the course of about two years, Janelia’s vivarium staff would clear the room for them, and then the team would reassemble the maze and set up video cameras and electrophysiology equipment. The team recorded the activity of individual cells in the hippocampus as rats explored the maze for the first time. They first introduced the animals to a small portion of the maze, then gradually increased the territory to which the rats had access, monitoring how the brain added new information to its spatial map.

When the scientists analyzed their data, they discovered that from the time the rats entered the maze, their brains were ready to represent an environment of any size. “Instead of the hippocampus having to adjust in time as the animal notices that the maze gets larger, it anticipates all different sizes of mazes from the beginning,” Lee says. “It does this by dividing up its population of neurons so that certain ones are ready to represent smaller mazes, others are ready to represent medium-size mazes, and others, large ones.”

All of the neurons acted independently, firing randomly to mark off places in the maze. But some neurons had a greater propensity to mark off space than others, Lee explains. Some neurons mark space quickly and become associated with many places in the maze, whereas others are less likely to fire. These, Lee says, are reserved for mapping larger spaces.

In small environments, a subset of the cells that are most likely to mark off space – those that have a chance to fire while the animal explores – form the map on their own. In larger mazes, all of the neurons with a high propensity to mark space are recruited to the mapping effort, meaning they cannot be used to distinguish the representation of one large maze from another. That’s when the neurons with a lower tendency to fire step in, randomly marking space in a distinct, identifying set.

“There’s always a set of neurons that is just at the edge, where they are equally likely to represent any given environment versus not, regardless of what its size is,” Lee says. “Those are the neurons the brain can actually use to distinguish which environment its in.”

The system means the brain never has to adjust its representation of an environment as it is being created, Lee says. “All neurons are marking space at their own preferred rate, so there doesn’t have to be a mechanism to say, ‘you should fire because this maze is large or this maze is small.’ The hippocampus is ready for anything at any moment.”

Cells in the human brain may record events in a similar way, marking off time as an event unfolds without knowing how long it will continue, Lee says.

Filed under hippocampus neural activity place cells neurons memory neuroscience science

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Can We Reconcile the Declarative Memory and Spatial Navigation Views on Hippocampal Function?
Some argue that hippocampus supports declarative memory, our capacity to recall facts and events, whereas others view the hippocampus as part of a system dedicated to calculating routes through space, and these two contrasting views are pursued largely independently in current research. Here we offer a perspective on where these views can and cannot be reconciled and update a bridging framework that will improve our understanding of hippocampal function.
Full Article

Can We Reconcile the Declarative Memory and Spatial Navigation Views on Hippocampal Function?

Some argue that hippocampus supports declarative memory, our capacity to recall facts and events, whereas others view the hippocampus as part of a system dedicated to calculating routes through space, and these two contrasting views are pursued largely independently in current research. Here we offer a perspective on where these views can and cannot be reconciled and update a bridging framework that will improve our understanding of hippocampal function.

Full Article

Filed under hippocampus memory spatial navigation neuroscience science

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Physically fit kids have beefier brain white matter than their less-fit peers
A new study of 9- and 10-year-olds finds that those who are more aerobically fit have more fibrous and compact white-matter tracts in the brain than their peers who are less fit. “White matter” describes the bundles of axons that carry nerve signals from one brain region to another. More compact white matter is associated with faster and more efficient nerve activity.
The team reports its findings in the open-access journal Frontiers in Human Neuroscience.
“Previous studies suggest that children with higher levels of aerobic fitness show greater brain volumes in gray-matter brain regions important for memory and learning,” said University of Illinois postdoctoral researcher Laura Chaddock-Heyman, who conducted the study with kinesiology and community health professor Charles Hillman and psychology professor and Beckman Institute director Arthur Kramer. “Now for the first time we explored how aerobic fitness relates to white matter in children’s brains.”
The team used diffusion tensor imaging (DTI, also called diffusion MRI) to look at five white-matter tracts in the brains of the 24 participants. This method analyzes water diffusion into tissues. For white matter, less water diffusion means the tissue is more fibrous and compact, both desirable traits.
The researchers controlled for several variables – such as social and economic status, the timing of puberty, IQ, or a diagnosis of ADHD or other learning disabilities – that might have contributed to the reported fitness differences in the brain.
The analysis revealed significant fitness-related differences in the integrity of several white-matter tracts in the brain: the corpus callosum, which connects the brain’s left and right hemispheres; the superior longitudinal fasciculus, a pair of structures that connect the frontal and parietal lobes; and the superior corona radiata, which connect the cerebral cortex to the brain stem.  “All of these tracts have been found to play a role in attention and memory,” Chaddock-Heyman said.
The team did not test for cognitive differences in the children in this study, but previous work has demonstrated a link between improved aerobic fitness and gains in cognitive function on specific tasks and in academic settings.
“Previous studies in our lab have reported a relationship between fitness and white-matter integrity in older adults,” Kramer said. “Therefore, it appears that fitness may have beneficial effects on white matter throughout the lifespan.”
To take the findings further, the team is now two years into a five-year randomized, controlled trial to determine whether white-matter tract integrity improves in children who begin a new physical fitness routine and maintain it over time. The researchers are looking for changes in aerobic fitness, brain structure and function, and genetic regulation.
“Prior work from our laboratories has demonstrated both short- and long-term differences in the relation of aerobic fitness to brain health and cognition,” Hillman said. “However, our current randomized, controlled trial should provide the most comprehensive assessment of this relationship to date.”
The new findings add to the evidence that aerobic exercise changes the brain in ways that improve cognitive function, Chaddock-Heyman said.
“This study extends our previous work and suggests that white-matter structure may be one additional mechanism by which higher-fit children outperform their lower-fit peers on cognitive tasks and in the classroom,” she said.

Physically fit kids have beefier brain white matter than their less-fit peers

A new study of 9- and 10-year-olds finds that those who are more aerobically fit have more fibrous and compact white-matter tracts in the brain than their peers who are less fit. “White matter” describes the bundles of axons that carry nerve signals from one brain region to another. More compact white matter is associated with faster and more efficient nerve activity.

The team reports its findings in the open-access journal Frontiers in Human Neuroscience.

“Previous studies suggest that children with higher levels of aerobic fitness show greater brain volumes in gray-matter brain regions important for memory and learning,” said University of Illinois postdoctoral researcher Laura Chaddock-Heyman, who conducted the study with kinesiology and community health professor Charles Hillman and psychology professor and Beckman Institute director Arthur Kramer. “Now for the first time we explored how aerobic fitness relates to white matter in children’s brains.”

The team used diffusion tensor imaging (DTI, also called diffusion MRI) to look at five white-matter tracts in the brains of the 24 participants. This method analyzes water diffusion into tissues. For white matter, less water diffusion means the tissue is more fibrous and compact, both desirable traits.

The researchers controlled for several variables – such as social and economic status, the timing of puberty, IQ, or a diagnosis of ADHD or other learning disabilities – that might have contributed to the reported fitness differences in the brain.

The analysis revealed significant fitness-related differences in the integrity of several white-matter tracts in the brain: the corpus callosum, which connects the brain’s left and right hemispheres; the superior longitudinal fasciculus, a pair of structures that connect the frontal and parietal lobes; and the superior corona radiata, which connect the cerebral cortex to the brain stem.
“All of these tracts have been found to play a role in attention and memory,” Chaddock-Heyman said.

The team did not test for cognitive differences in the children in this study, but previous work has demonstrated a link between improved aerobic fitness and gains in cognitive function on specific tasks and in academic settings.

“Previous studies in our lab have reported a relationship between fitness and white-matter integrity in older adults,” Kramer said. “Therefore, it appears that fitness may have beneficial effects on white matter throughout the lifespan.”

To take the findings further, the team is now two years into a five-year randomized, controlled trial to determine whether white-matter tract integrity improves in children who begin a new physical fitness routine and maintain it over time. The researchers are looking for changes in aerobic fitness, brain structure and function, and genetic regulation.

“Prior work from our laboratories has demonstrated both short- and long-term differences in the relation of aerobic fitness to brain health and cognition,” Hillman said. “However, our current randomized, controlled trial should provide the most comprehensive assessment of this relationship to date.”

The new findings add to the evidence that aerobic exercise changes the brain in ways that improve cognitive function, Chaddock-Heyman said.

“This study extends our previous work and suggests that white-matter structure may be one additional mechanism by which higher-fit children outperform their lower-fit peers on cognitive tasks and in the classroom,” she said.

Filed under white matter diffusion tensor imaging aerobic fitness cognitive function memory neuroscience science

120 notes

The role of lactate in boosting memory

Everyone knows that neurons are the key to how the brain operates. But it turns out they aren’t the only stars in the show; neighboring cells called astrocytes are quickly gaining increasing respect for the critical role they play in memory and learning. EPFL scientists have recently outlined the molecular mechanics of this process in an article published in Proceedings of the National Academy of Sciences (PNAS). Lactate produced by the star-shaped astrocytes accelerates the memorization process. This result, surprising until very recently, opens up new possibilities for treating cognitive and memory disorders, as well as psychiatric conditions such as depression.

Our brains are greedy, gobbling up as much as 25% of our daily energy consumption. Neurons and astrocytes thrive on glucose. Neurons use it to protect themselves from the buildup of toxic products resulting from their activity. Astrocytes, which are glial cells (as opposed to neurons), manufacture lactate; this was long thought to be a byproduct of glucose metabolism, and then as a simple energy source for neurons.

In 2011, research published in the journal Cell by EPFL’s Laboratory of Neuroenergetics and Cellular Dynamics in collaboration with a U.S. team unveiled the critical role of lactate. “In vivo, when the transfer of lactate from astrocytes to neurons is blocked, we found that the memorization process was also blocked,” explains EPFL professor Pierre Magistretti, head of the lab. “We thus knew that it was an essential fuel for that process.”

Focusing their attention on the molecular mechanism, the scientists discovered that lactate provides more than just energy. It acts as a moderator of one type of glutamate receptor (NMDA receptors), the nervous system’s primary neurotransmitter. This glutamate receptor is involved in the memorization process, and the research demonstrates that lactate gives them what amounts to a turbo-boost. “Glutamate lets you drive in first gear; with lactate, you can shift into fourth and travel at 100 km/h,” says Magistretti.

Palliating cognitive deficits
The scientists did their initial research in vitro. They exposed mice neurons to various substances and measured their effect on the expression of genes involved in memory. Glucose and pyruvate (another glucose derivative) didn’t have any effect. A lactate supplement, on the other hand, triggered the expression of four genes involved in cerebral plasticity that are essential to memorization.

They followed this work with in vivo studies, which confirmed their results. They administered lactate into the brains of living mice, and then extracted the tissues and measured gene expression. Once again, the expression of genes involved in cerebral plasticity increased significantly.

Could we take lactate supplements and develop encyclopedic memory? Magistretti’s lab has just received a grant to study the effects of artificial lactate supplementation. “We have identified a series of molecules that can make astrocytes produce more lactate. Now the idea is to see in vivo if we can mitigate cognitive deficits and memory disorders.” In addition, since conditions such as depression are often accompanied by cognitive problems, “lactate could also have an antidepressant effect,” says Magistretti, who also conducts research at the National Center for Competence in Research Synapsy, dedicated to the understanding of the synaptic basis of psychiatric disease.

(Source: actu.epfl.ch)

Filed under astrocytes memory glucose NMDA receptors lactate synaptic plasticity neuroscience science

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