Posts tagged hippocampus
Articles and news from the latest research reports.
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.
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)
Weird: Nuclear Bomb Tests Reveal Adults Grow New Brain Cells
Aboveground nuclear bomb testing in the 1950s and 1960s inadvertently gave modern scientists a way to prove the adult brain regularly creates new neurons, research reveals.
Researchers used to believe that the brain changed little once it finished maturing. That view is now considered out of date, as studies have revealed how changeable — or plastic — the adult brain can be.
Much of this plasticity is related to the brain’s organization; brain cells can alter their connections and communications with other brain cells. What has been less clear is whether, and to what extent, the human brain grows brand-new neurons in adulthood.
"There was a lot in the literature showing there was neurogenesis in rodents and every animal studied," said study researcher Kirsty Spalding, a biologist at the Karolinska Institute in Sweden, "But there was very little evidence of whether this happens in humans."
Tantalizing clues
Scientists had reason to believe it does. In adult mice, the hippocampus, a structure deep in the brain involved in memory and navigation, turns over cells all the time. Some of the biological markers linked to this turnover are seen in the human hippocampus. But the only direct evidence of new brain cells forming in the region came from a 1998 study in which researchers looked at the brains of five people who had been injected with a compounded called BrdU that cells take up into their DNA. (The compound was once used in experimental cancer studies, but is not used anymore for safety reasons.)
The BrdU study revealed that neurons in the hippocampuses of the participants contained the compound in their DNA, indicating these brain cells had formed after the injections. The oldest person in the study was 72, suggesting new neuron creation, known as neurogenesis, continues well into old age.
The 1998 study was the only direct evidence of such neurogenesis in the human hippocampus, however. Spalding and her colleagues wanted to change that. Ten years ago, they began a project to track the age of neurons in the human brain using an unusual tool: spare molecules left over from Cold War-era nuclear bomb tests.
Learning to love the bomb
Between 1945 and 1962, the United States conducted hundreds of aboveground nuclear bomb tests. These tests largely stopped with the Limited Test Ban Treaty of 1963, but their effects remained in the atmosphere. The neutrons sent flying by the bombs reacted with nitrogen in the atmosphere, creating a spike in carbon 14, an isotope (or variation) of carbon.
This carbon 14, in turn, did what carbon in the atmosphere does. It combined with oxygen to form carbon dioxide, and was then taken in by plants, which use carbon dioxide in photosynthesis. Humans ate some of these plants, along with some of the animals that also ate these plants, and the carbon 14 inside ended up in their bodies.
When a cell divides, it uses this carbon 14, integrating it into the DNA of the new cells that are forming. Carbon 14 decays over time at a known rate, so scientists can pinpoint from that decay exactly when the new cells were born.
Over the past decade, Spalding and her colleagues have used the technique in a variety of cells, including fat cells, refining it along the way until it became sensitive enough to measure tiny amounts of carbon 14 in small hippocampus samples. The researchers collected samples, with family permission, from autopsies in Sweden.
They found the tantalizing 1998 evidence was correct: Human hippocampuses do grow new neurons. In fact, about a third of the brain region is subject to cell turnover, with about 700 new neurons being formed each day in each hippocampus (humans have two, a mirror-image set on either side of the brain). Hippocampus neurons die each day, too, keeping the overall number more or less in balance, with some slow loss of cells with aging, Spalding said.
This turnover occurs at a ridge in the hippocampus known as the dentate gyrus, a spot known to contribute to the formation of new memories. Researchers aren’t sure what the function of this constant renewal is, but it could relate to allowing the brain to cope with novel situations, Spalding told LiveScience.
"Neurogenesis gives a particular kind of plasticity to the brain, a cognitive flexibility," she said.
Spalding and her colleagues had used the same techniques in other regions of the brain, including the cortex, the cerebellum and the olfactory bulb, and found no evidence of newborn neurons being integrated into those areas. The researchers now plan to study whether there are any links between neurogenesis and psychiatric conditions such as depression.
The new findings are detailed in the journal Cell.
Manipulating Memory in the Hippocampus
Protein modification may help control Alzheimer’s and epilepsy, TAU researchers find
In the brain, cell-to-cell communication is dependent on neurotransmitters, chemicals that aid the transfer of information between neurons. Several proteins have the ability to modify the production of these chemicals by either increasing or decreasing their amount, or promoting or preventing their secretion. One example is tomosyn, which hinders the secretion of neurotransmitters in abnormal amounts.
Dr. Boaz Barak of Tel Aviv University’s Sagol School of Neuroscience, in collaboration with Prof. Uri Ashery, used a method for modifying the levels of this protein in the mouse hippocampus — the region of the brain associated with learning and memory. It had a significant impact on the brain’s activity: Over-production of the protein led to a sharp decline in the ability to learn and memorize information, the researchers reported in the journal NeuroMolecular Medicine.
"This study demonstrates that it is possible to manipulate various processes and neural circuits in the brain," says Dr. Barak, a finding which may aid in the development of therapeutic procedures for epilepsy and neurodegenerative diseases such as Alzheimer’s. Slowing the transmission rate of information when the brain is overactive during epileptic seizures could have a beneficial effect, and readjusting the levels of tomosyn in an Alzheimer’s patient may help increase cognition and combat memory loss.
A maze of memory loss
The researchers teamed up with a laboratory at the National Institutes of Health (NIH) in Baltimore to create a virus which produces the tomosyn protein. In the lab, the virus was injected into the hippocampus region in mice. Then, in order to test the consequences, they performed a series of behavioral tests designed to measure functions like memory, cognitive ability, and motor skills.
In one experiment, called the Morris Water Maze, mice had to learn to navigate to, and remember, the location of a hidden platform placed inside a pool with opaque water. During the first five days of testing, researchers found that the test group with an over-production of tomosyn had a significant problem in learning and memorizing the location of the platform, compared to a control group that received a placebo injection. And when the platform was removed from the maze, the test group spent less time swimming around the area where the platform once was, indicating that they had no memory of its existence. In comparison, the control group of mice searched for the missing platform in its previous location for two or even three days after its removal, notes Dr. Barak.
These findings were further verified by measuring electrical activity in the brains of both the test group and the control group. In the test group, researchers found decreased levels of transmissions between neurons in the hippocampus, a physiological finding that may explain the results of the behavioral tests.
Correcting neuronal processes
In the future, Dr. Barak believes that the ability to modify proteins directly in the brain will allow for more control over brain activities and the correction of neurodegenerative processes, such as providing stricter regulation in neuronal activity for epileptic patients or stimulating neurotransmitters to help with learning and memory loss in Alzheimer’s patients. Indeed, a separate study conducted by the researchers demonstrates that mouse models for Alzheimer’s disease do have an over-production of tomosyn in the hippocampus region, so countering the production of this protein could have a beneficial effect.
Now Dr. Barak and Prof. Ashery are working towards a method for artificially decreasing levels of the protein, which they believe will have the opposite effect on the cognitive ability of the mice. “We hypothesize that with an under-production in tomosyn, the mice will show a marked improvement in their performance in behavioral testing,” he says.
(Source: aftau.org)
Study shows emotional contagion increases in Alzheimer’s patients
A team of researchers working at the University of California’s Memory and Aging Center has found that emotional contagion appears to increase in a linear progression with patients who have Alzheimer’s disease (AD). In their paper published in the journal Proceedings of the National Academy of Sciences, the team says their findings indicate that emotional contagion grows stronger in patients with both the precursor Mild Cognitive Impairment (MCI) and full-blown AD.
Emotional contagion is where one person mimics the emotions of another. The phenomenon is very common in human infants—upon seeing someone else smile, they tend to smile too. Babies have also been found to cry upon hearing other babies cry. The tendency to mimic others’ emotions regresses as people age, but this new study suggests it makes a reappearance in people who experience some forms of cognitive impairment later on in life.
Prior research has shown that AD causes damage to parts of the brain that are responsible for emotion—thus not all emotional problems with AD patients can be attributed to a natural human response to mental adversity. Both MCI and AD patients have been found to experience higher rates of depression and anxiety. Until now however, little research has been done to find out if people revert to mimicking the emotions of others as a type of response mechanism.
To learn more, the researchers performed psychological surveys on 120 people diagnosed with AD or MCI. Their inquiries focused mostly on emotional empathy. The team also enlisted the assistance of 111 healthy volunteers to serve as a control group. All of the participants also underwent MRI exams to test for levels of disease progression.
The brain scans revealed damage to the medial temporal lobe—known to be associated with emotional control—in those with dementia and also in the hippocampus, the part of the brain responsible for memory and recall.
An analysis of the results of the surveys and brain scans showed that emotional contagion became apparent in patients with MCI and grew more pronounced at each stage of the progression of AD. They also found that there appeared to be more of a connection between the degree of emotional contagion and damage to the right side of the medial temporal lobe, as compared to the left.
The researchers suggest that patients with dementia may mimic the emotions of others as their ability to gauge their own emotional state deteriorates. Doing so, they suggest, may help patients cope with their ailment. They add they it may also help patients hide their condition from others.
(Source: medicalxpress.com)
New neuron formation could increase capacity for new learning, at the expense of old memories
Cause of infantile amnesia revealed
New research presented today shows that formation of new neurons in the hippocampus - a brain region known for its importance in learning and remembering - could cause forgetting of old memories by causing a reorganization of existing brain circuits. Drs. Paul Frankland and Sheena Josselyn, both from the Hospital for Sick Children in Toronto, argue this reorganization could have the positive effect of clearing old memories, reducing interference and thereby increasing capacity for new learning. These results were presented at the 2013 Canadian Neuroscience Meeting, the annual meeting of the Canadian Association for Neuroscience - Association Canadienne des Neurosciences (CAN-ACN).
Researchers have long known of the phenomenon of infantile amnesia: This refers to the absence of long-term memory of events occurring within the first 2-3 years of life, and little long-term memories for events occurring until about 7 years of age. Studies have shown that though young children can remember events in the short term, these memories do not persist. This new study by Frankland and Josselyn shows that this amnesia is associated with high levels of new neuron production - a process called neurogenesis - in the hippocampus, and that more permanent memory formation is associated with a reduction in neurogenesis.
Dr. Frankland and Dr. Josselyn’s approach was to look at retention of memories in young mice in which they suppressed the usual high levels of neurogenesis in the hippocampus (thereby replicating the circuit stability normally observed in adult mice), but also in older mice in which they stimulated increased neurogenesis (thereby replicating the conditions normally seen in younger mice). Dr. Frankland was able to show a causal relationship between a reduction in neurogenesis and increased remembering, and the converse, decreased remembering when neurogenesis increased.
Dr. Frankland concludes: ” Why infantile amnesia exists has long been a mystery. We think our new studies begin to explain why we have no memories from our earliest years.”
Genetic Predictors of Postpartum Depression Uncovered
Alteration of two genes, detectable by simple blood test during pregnancy, foretold illness with 85 percent certainty in small study
Johns Hopkins researchers say they have discovered specific chemical alterations in two genes that, when present during pregnancy, reliably predict whether a woman will develop postpartum depression.
The epigenetic modifications, which alter the way genes function without changing the underlying DNA sequence, can apparently be detected in the blood of pregnant women during any trimester, potentially providing a simple way to foretell depression in the weeks after giving birth, and an opportunity to intervene before symptoms become debilitating.
The findings of the small study involving 52 pregnant women are described online in the journal Molecular Psychiatry.
“Postpartum depression can be harmful to both mother and child,” says study leader Zachary Kaminsky, Ph.D., an assistant professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine. “But we don’t have a reliable way to screen for the condition before it causes harm, and a test like this could be that way.”
It is not clear what causes postpartum depression, a condition marked by persistent feelings of sadness, hopelessness, exhaustion and anxiety that begins within four weeks of childbirth and can last weeks, several months or up to a year. An estimated 10 to 18 percent of all new mothers develop the condition, and the rate rises to 30 to 35 percent among women with previously diagnosed mood disorders. Scientists long believed the symptoms were related to the large drop-off in the mother’s estrogen levels following childbirth, but studies have shown that both depressed and nondepressed women have similar estrogen levels.
By studying mice, the Johns Hopkins researchers suspected that estrogen induced epigenetic changes in cells in the hippocampus, a part of the brain that governs mood. Kaminsky and his team then created a complicated statistical model to find the candidate genes most likely undergoing those epigenetic changes, which could be potential predictors for postpartum depression. That process resulted in the identification of two genes, known as TTC9B and HP1BP3, about which little is known save for their involvement in hippocampal activity.
Kaminsky says the genes in question may have something to do with the creation of new cells in the hippocampus and the ability of the brain to reorganize and adapt in the face of new environments — two elements important in mood. In some ways, he says, estrogen can behave like an antidepressant, so that when inhibited, it adversely affects mood.
The researchers later confirmed their findings in humans by looking for epigenetic changes to thousands of genes in blood samples from 52 pregnant women with mood disorders. Jennifer L. Payne, M.D., director of the Johns Hopkins Women’s Mood Disorders Center, collected the blood samples. The women were followed both during and after pregnancy to see who developed postpartum depression.
The researchers noticed that women who developed postpartum depression exhibited stronger epigenetic changes in those genes that are most responsive to estrogen, suggesting that these women are more sensitive to the hormone’s effects. Specifically, two genes were most highly correlated with the development of postpartum depression. TTC9B and HP1BP3 predicted with 85 percent certainty which women became ill.
“We were pretty surprised by how well the genes were correlated with postpartum depression,” Kaminsky says. “With more research, this could prove to be a powerful tool.”
Kaminsky says the next step in research would be to collect blood samples from a larger group of pregnant women and follow them for a longer period of time. He also says it would be useful to examine whether the same epigenetic changes are present in the offspring of women who develop postpartum depression.
Evidence suggests that early identification and treatment of postpartum depression can limit or prevent debilitating effects. Alerting women to the condition’s risk factors — as well as determining whether they have a previous history of the disorder, other mental illness and unusual stress — is key to preventing long-term problems.
Research also shows, Kaminsky says, that postpartum depression not only affects the health and safety of the mother, but also her child’s mental, physical and behavioral health.
Kaminsky says that if his preliminary work pans out, he hopes a blood test for the epigenetic biomarkers could be added to the battery of tests women undergo during pregnancy, and inform decisions about the use of antidepressants during pregnancy. There are concerns, he says, about the effects of these drugs on the fetus and their use must be weighed against the potentially debilitating consequences to both the mother and child of foregoing them.
“If you knew you were likely to develop postpartum depression, your decisions about managing your care could be made more clearly,” he says.
(Source: hopkinsmedicine.org)
Brain rewires itself after damage or injury
When the brain’s primary “learning center” is damaged, complex new neural circuits arise to compensate for the lost function, say life scientists from UCLA and Australia who have pinpointed the regions of the brain involved in creating those alternate pathways — often far from the damaged site.
The research, conducted by UCLA’s Michael Fanselow and Moriel Zelikowsky in collaboration with Bryce Vissel, a group leader of the neuroscience research program at Sydney’s Garvan Institute of Medical Research, appears this week in the early online edition of the journal Proceedings of the National Academy of Sciences.
The researchers found that parts of the prefrontal cortex take over when the hippocampus, the brain’s key center of learning and memory formation, is disabled. Their breakthrough discovery, the first demonstration of such neural-circuit plasticity, could potentially help scientists develop new treatments for Alzheimer’s disease, stroke and other conditions involving damage to the brain.
For the study, Fanselow and Zelikowsky conducted laboratory experiments with rats showing that the rodents were able to learn new tasks even after damage to the hippocampus. While the rats needed more training than they would have normally, they nonetheless learned from their experiences — a surprising finding.
"I expect that the brain probably has to be trained through experience," said Fanselow, a professor of psychology and member of the UCLA Brain Research Institute, who was the study’s senior author. "In this case, we gave animals a problem to solve."
After discovering the rats could, in fact, learn to solve problems, Zelikowsky, a graduate student in Fanselow’s laboratory, traveled to Australia, where she worked with Vissel to analyze the anatomy of the changes that had taken place in the rats’ brains. Their analysis identified significant functional changes in two specific regions of the prefrontal cortex.
"Interestingly, previous studies had shown that these prefrontal cortex regions also light up in the brains of Alzheimer’s patients, suggesting that similar compensatory circuits develop in people," Vissel said. "While it’s probable that the brains of Alzheimer’s sufferers are already compensating for damage, this discovery has significant potential for extending that compensation and improving the lives of many."
The hippocampus, a seahorse-shaped structure where memories are formed in the brain, plays critical roles in processing, storing and recalling information. The hippocampus is highly susceptible to damage through stroke or lack of oxygen and is critically inolved in Alzheimer’s disease, Fanselow said.
"Until now, we’ve been trying to figure out how to stimulate repair within the hippocampus," he said. "Now we can see other structures stepping in and whole new brain circuits coming into being."
Zelikowsky said she found it interesting that sub-regions in the prefrontal cortex compensated in different ways, with one sub-region — the infralimbic cortex — silencing its activity and another sub-region — the prelimbic cortex — increasing its activity.
"If we’re going to harness this kind of plasticity to help stroke victims or people with Alzheimer’s," she said, "we first have to understand exactly how to differentially enhance and silence function, either behaviorally or pharmacologically. It’s clearly important not to enhance all areas. The brain works by silencing and activating different populations of neurons. To form memories, you have to filter out what’s important and what’s not."
Complex behavior always involves multiple parts of the brain communicating with one another, with one region’s message affecting how another region will respond, Fanselow noted. These molecular changes produce our memories, feelings and actions.
"The brain is heavily interconnected — you can get from any neuron in the brain to any other neuron via about six synaptic connections," he said. "So there are many alternate pathways the brain can use, but it normally doesn’t use them unless it’s forced to. Once we understand how the brain makes these decisions, then we’re in a position to encourage pathways to take over when they need to, especially in the case of brain damage.
"Behavior creates molecular changes in the brain; if we know the molecular changes we want to bring about, then we can try to facilitate those changes to occur through behavior and drug therapy," he added. I think that’s the best alternative we have. Future treatments are not going to be all behavioral or all pharmacological, but a combination of both."
All mammals sleep, as do birds and some insects. However, how this basic function is regulated by the brain remains unclear. According to a new study by researchers from the RIKEN Brain Science Institute, a brain region called the lateral habenula plays a central role in the regulation of REM sleep. In an article published today in the Journal of Neuroscience, the team shows that the lateral habenula maintains and regulates REM sleep in rats through regulation of the serotonin system. This study is the first to show a role of the lateral habenula in linking serotonin metabolism and sleep.
The lateral habenula is a region of the brain known to regulate the metabolism of the neurotransmitter serotonin in the brain and to play a key role in cognitive functions.
“Serotonin plays a central role in the pathophysiology of depression, however, it is not clear how abnormalities in regulation of serotonin metabolism in the brain lead to symptoms such as insomnia in depression,” explain Dr. Hidenori Aizawa and Dr. Hitoshi Okamoto who led the study.
Since animals with increased serotonergic activity at the synapse experienced less REM sleep, the researchers hypothesized that the lateral habenula, which regulates serotonergic activity in the brain, must modulate the duration of REM sleep.
They show that removing the lateral habenula in rats results in a reduction of theta rhythm, an oscillatory activity that appears during REM sleep, in the hippocampus, and shortens the rats’ REM sleep periods. However, this inhibitory effect of the lateral habenular lesion on REM sleep disappears when the serotonergic neurons in the midbrain are lesioned.
The team recorded neural activity simultaneously in the lateral habenula and hippocampus in a sleeping rat. They find that the lateral habenular neurons, which fire persistently during non-REM sleep, begin to fire rhythmically in accordance with the theta rhythm in the hippocampus when the animal is in REM sleep.
“Our results indicate that the lateral habenula is essential for maintaining theta rhythms in the hippocampus, which characterize REM sleep in the rat, and that this is done via serotonergic modulation,” concludes Dr Aizawa.
“This study reveals a novel role of the lateral habenula, linking serotonin and REM sleep, which suggests that an hyperactive habenula in patients with depression may cause altered REM sleep,” add the authors.
Serotonin Mediates Exercise-Induced Generation of New Neurons
Mice that exercise in running wheels exhibit increased neurogenesis in the brain. Crucial to this process is serotonin signaling. These are the findings of a study by Dr. Friederike Klempin, Daniel Beis and Dr. Natalia Alenina from the research group led by Professor Michael Bader at the Max Delbrück Center (MDC) Berlin-Buch. Surprisingly, mice lacking brain serotonin due to a genetic mutation exhibited normal baseline neurogenesis. However, in these serotonin-deficient mice, activity-induced proliferation was impaired, and wheel running did not induce increased generation of new neurons. (Journal of Neuroscience)
Scientists have known for some time that exercise induces neurogenesis in a specific brain region, the hippocampus. However, until this study, the underlying mechanism was not fully understood. The hippocampus plays an important role in learning and in memory and is one of the brain regions where new neurons are generated throughout life.
Serotonin facilitates precursor cell maturation
The researchers demonstrated that mice with the ability to produce serotonin are likely to release more of this hormone during exercise, which in turn increases cell proliferation of precursor cells in the hippocampus. Furthermore, serotonin seems to facilitate the transition of stem to progenitor cells that become neurons in the adult mouse brain.
For Dr. Klempin and Dr. Alenina it was surprising that normal baseline neurogenesis occurs in mice that, due to a genetic mutation, cannot produce serotonin in the brain. However, they noted that some of the stem cells in serotonin-deficient mice either die or fail to become neurons.
Yet, these animals seem to have a mechanism that allows compensation for the deficit, in that progenitor cells, an intermediate stage in the development from a stem cell to a neuron, divide more frequently. According to the researchers, this is to maintain the pool of these cells.
However, the group of wheel-running mice that do not produce serotonin did not exhibit an exercise-induced increase in neurogenesis. The compensatory mechanism failed following running. The researchers concluded: “Serotonin is not necessarily required for baseline generation of new neurons in the adult brain, but is essential for exercise-induced hippocampal neurogenesis.”
Hope for new approaches to treat depression and memory loss in the elderly
Deficiency in serotonin, popularly known as the “molecule of happiness”, has been considered in the context of theories linking major depression to declining neurogenesis in the adult brain. “Our findings could potentially help to develop new approaches to prevent and treat depression as well as age-related decline in learning and memory,” said Dr. Klempin and Dr. Alenina.
Brain implants: Restoring memory with a microchip
William Gibson’s popular science fiction tale “Johnny Mnemonic” foresaw sensitive information being carried by microchips in the brain by 2021. A team of American neuroscientists could be making this fantasy world a reality.
Their motivation is different but the outcome would be somewhat similar. Hailed as one of 2013’s top ten technological breakthroughs by MIT, the work by the University of Southern California, North Carolina’s Wake Forest University and other partners has actually spanned a decade.
But the U.S.-wide team now thinks that it will see a memory device being implanted in a small number of human volunteers within two years and available to patients in five to 10 years. They can’t quite contain their excitement.
"I never thought I’d see this in my lifetime," said Ted Berger, professor of biomedical engineering at the University of Southern California in Los Angeles. "I might not benefit from it myself but my kids will."
Rob Hampson, associate professor of physiology and pharmacology at Wake Forest University, agrees. “We keep pushing forward, every time I put an estimate on it, it gets shorter and shorter.”
The scientists — who bring varied skills to the table, including mathematical modeling and psychiatry — believe they have cracked how long-term memories are made, stored and retrieved and how to replicate this process in brains that are damaged, particularly by stroke or localized injury.
Berger said they record a memory being made, in an undamaged area of the brain, then use that data to predict what a damaged area “downstream” should be doing. Electrodes are then used to stimulate the damaged area to replicate the action of the undamaged cells.
They concentrate on the hippocampus — part of the cerebral cortex which sits deep in the brain — where short-term memories become long-term ones. Berger has looked at how electrical signals travel through neurons there to form those long-term memories and has used his expertise in mathematical modeling to mimic these movements using electronics.
Hampson, whose university has done much of the animal studies, adds: “We support and reinforce the signal in the hippocampus but we are moving forward with the idea that if you can study enough of the inputs and outputs to replace the function of the hippocampus, you can bypass the hippocampus.”
The team’s experiments on rats and monkeys have shown that certain brain functions can be replaced with signals via electrodes. You would think that the work of then creating an implant for people and getting such a thing approved would be a Herculean task, but think again.
For 15 years, people have been having brain implants to provide deep brain stimulation to treat epilepsy and Parkinson’s disease — a reported 80,000 people have now had such devices placed in their brains. So many of the hurdles have already been overcome — particularly the “yuck factor” and the fear factor.
"It’s now commonly accepted that humans will have electrodes put in them — it’s done for epilepsy, deep brain stimulation, (that has made it) easier for investigative research, it’s much more acceptable now than five to 10 years ago," Hampson says.
Much of the work that remains now is in shrinking down the electronics.
"Right now it’s not a device, it’s a fair amount of equipment,"Hampson says. "We’re probably looking at devices in the five to 10 year range for human patients."
The ultimate goal in memory research would be to treat Alzheimer’s Disease but unlike in stroke or localized brain injury, Alzheimer’s tends to affect many parts of the brain, especially in its later stages, making these implants a less likely option any time soon.
Berger foresees a future, however, where drugs and implants could be used together to treat early dementia. Drugs could be used to enhance the action of cells that surround the most damaged areas, and the team’s memory implant could be used to replace a lot of the lost cells in the center of the damaged area. “I think the best strategy is going to involve both drugs and devices,” he says.
Unfortunately, the team found that its method can’t help patients with advanced dementia.
"When looking at a patient with mild memory loss, there’s probably enough residual signal to work with, but not when there’s significant memory loss," Hampson said.
Constantine Lyketsos, professor of psychiatry and behavioral sciences at John Hopkins Medicine in Baltimore which is trialing a deep brain stimulator implant for Alzheimer’s patients was a little skeptical of the other team’s claims.
"The brain has a lot of redundancy, it can function pretty well if loses one or two parts. But memory involves circuits diffusely dispersed throughout the brain so it’s hard to envision." However, he added that it was more likely to be successful in helping victims of stroke or localized brain injury as indeed its makers are aiming to do.
The UK’s Alzheimer’s Society is cautiously optimistic.
"Finding ways to combat symptoms caused by changes in the brain is an ongoing battle for researchers. An implant like this one is an interesting avenue to explore," said Doug Brown, director of research and development.
Hampson says the team’s breakthrough is “like the difference between a cane, to help you walk, and a prosthetic limb — it’s two different approaches.”
It will still take time for many people to accept their findings and their claims, he says, but they don’t expect to have a shortage of volunteers stepping forward to try their implant — the project is partly funded by the U.S. military which is looking for help with battlefield injuries.
There are U.S. soldiers coming back from operations with brain trauma and a neurologist at DARPA (the Defense Advanced Research Projects Agency) is asking “what can you do for my boys?” Hampson says.
"That’s what it’s all about."