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Science Briefs

Flip of a single molecular switch makes an old brain younger →

The flip of a single molecular switch helps create the mature neuronal connections that allow the brain to bridge the gap between adolescent impressionability and adult stability. Now researchers have reversed the process, recreating a youthful brain that facilitated both learning and healing in adult mice. It’s long been known that the young and old brains are very different. Adolescent brains are more malleable or plastic, which allows them to learn languages more quickly than adults and speeds recovery from brain injuries. The comparative rigidity of the adult brain results in part from the function of a single gene that slows the rapid change in synaptic connections between neurons.

By monitoring the synapses in living mice over weeks and months, researchers have identified the key genetic switch for brain maturation. The Nogo Receptor 1 gene is required to suppress high levels of plasticity in the adolescent brain and create the relatively quiescent levels of plasticity in adulthood. In mice without this gene, juvenile levels of brain plasticity persist throughout adulthood. When researchers blocked the function of this gene in old mice, they reset the old brain to adolescent levels of plasticity.

“These are the molecules the brain needs for the transition from adolescence to adulthood,” said Stephen Strittmatter. senior author of the paper. “It suggests we can turn back the clock in the adult brain and recover from trauma the way kids recover.” Rehabilitation after brain injuries like strokes requires that patients re-learn tasks such as moving a hand. Researchers found that adult mice lacking Nogo Receptor recovered from injury as quickly as adolescent mice and mastered new, complex motor tasks more quickly than adults with the receptor. Researchers also showed that Nogo Receptor slows loss of memories. Mice without Nogo receptor lost stressful memories more quickly.

— 1 year ago with 2 notes
#neuroscience 
Human Astrocytes Make Mice Smarter →

Glial cells – a family of cells found in the human central nervous system and, until recently, considered mere housekeepers – now appear to promote the unique complexity of the human brain. This conclusion followed from a finding that when human astrocytes (a subtype of glia) were transplanted into mice they could improve communication in the brain, allowing the mice to learn more rapidly.

Astrocytes are far more abundant, larger, and diverse in human brain than in other species. In humans, individual astrocytes project scores of fibers that can simultaneously connect with large numbers of neurons. So individual human astrocytes can potentially coordinate the activity of thousands of synapses. This suggested that human astrocytes might play a significant role in integrating and coordinating the more complex signaling activity found in human brains, and hence help regulate higher cognitive functions. This in turn suggested that, when transplanted into mice, human glia may influence underlying patterns of neural activity.

The research team studied what happened when these cells were allowed to co-exist with the normal nerve cells of mice. They first isolated human glial progenitors, which give rise to astrocytes, from brain tissue. They then transplanted these into the brains of neonatal mice. As the mice matured, the human glial cells outcompeted the host’s native glia, while at the same time leaving the existing neural network intact.

The team then examined the functional impact that these cells had on the animals’ brains, specifically the speed and retention of signals between cells in the brain and its plasticity – the ability of the brain to form new memories and learn new tasks. They found that two important indicators of brain function drastically improved in the mice with human glia. First, the researchers noted that the speed of wave transmission in the transplanted mice was faster than normally observed in mice, and more similar to that of human brain tissue. Second, the researchers looked at long-term potentiation (LTP), a process that measures how long the neurons in the brain are affected by a brief electrical stimulation. The researchers found that the transplanted mice developed more rapid and sustained LTP, suggesting an improved learning capability. When the team evaluated the mice in a series of behavioral tasks to test memory and learning ability, they found that the transplanted mice were more rapid learners and both acquired new associations and performed a variety of tasks significantly faster than mice without the human glial cells.

More:

Mice Learn Faster with Human Glia
Mice get brain boost from transplanted human tissue
Human Brain Cells Boost Mouse Memory
Human Brain Cells Make Mice Smart
Mice Given Human Brain Cells Become Smarter
Human brain cells boost mouse memory
Glia brain cells: Not just infrastructure

— 1 year ago with 1 note
#neuroscience  #astrocytes 
Brain Imaging Research Shows How Unconscious Processing Improves Decision-Making →

When faced with a difficult decision, it is often suggested to “sleep on it” or take a break from thinking about the decision in order to gain clarity. New brain imaging research finds that the brain regions responsible for making decisions continue to be active even when the conscious brain is distracted with a different task. The research provides some of the first evidence showing how the brain unconsciously processes decision information in ways that lead to improved decision-making.

According to researcher J. David Creswell, the research “shows that brain regions important for decision-making remain active even while our brains may be simultaneously engaged in unrelated tasks, such as thinking about a math problem. What’s most intriguing about this finding is that participants did not have any awareness that their brains were still working on the decision problem while they were engaged in an unrelated task.” For the study, the researchers presented 27 healthy adults with information about cars and other items while undergoing neuroimaging. Then, before being asked to make decisions about the items, the participants had to complete a difficult distractor task to prevent them from consciously thinking about the decision information.

There were three main findings. First, the team confirmed previous research demonstrating that a brief period of distraction produced higher quality decisions. Did this effect occur because the distraction period provided an opportunity for the brain to take a break from decision-making and then return to the problem with a fresh look? Or alternatively, does the brain continue to unconsciously process decision information during this distraction period? The research supports the latter unconscious processing explanation.

When the participants were initially learning information, neuroimaging showed activation in the visual and prefrontal cortices, regions that are known to be responsible for learning and decision-making. Additionally, during the distractor task, both the visual and prefrontal cortices continued to be active even though the brain was consciously focused on number memorization. Third, the results showed that the amount of reactivation within the visual and prefrontal cortices during the distractor task predicted the degree to which participants made better decisions, such as picking the best car in the set.

— 1 year ago with 2 notes
#neuroscience  #consciousness 
Gene needed for proper synapse formation identified. →

A new study finds that DCC, the receptor for the nervous system protein netrin, plays a key role in regulating the plasticity of nerve cell connections in the brain. The absence of DCC leads to the type of memory loss experienced by the famous subject HM. Although HM’s memory loss resulted from the removal of an entire brain structure, this study shows that just removing DCC causes the same type of memory deficit. Although both netrin and DCC are essential for normal development (in terms of guiding nerve cell growth) until now their function in the adult brain was not known.

“We show that the netrin receptor DCC is a critical component of synapses between neurons in the adult brain, and is required for synapses to function properly,” lead researcher Tim Kennedy said. “To demonstrate this, we selectively removed DCC from a specific subset of neurons in the adult mouse brain. This results in progressive degeneration of synapses, leading to defects in synaptic plasticity and memory. The synapses continue to function in that they still communicate but, the synapses cannot adjust or change in response to new experiences. Therefore, you can’t learn anymore.”

Furthermore, DCC deletion from mature neurons results in changes in the shape of specialized protrusions (dendritic spines) on which synapses form, and alters the NMDA receptor, a critical trigger for mechanisms that make changes in synaptic strength. Therefore the study reveals that DCC is required to maintain proper synapse morphology or shape, and to regulate the ability of the NMDA receptor to switch on, which ensures activity-dependent synaptic plasticity.

Mutant mice that entirely lack DCC in all cells do not survive past birth and exhibit major defects in brain development. Using mice in which a special enzyme causes deletion of DCC genes, Kennedy’s lab activated this enzyme only in the mature mouse brain, and limited activation to only a subset of neurons, consequently deleting the DCC gene from only from these neurons. These mice live to adulthood (DCC is made normally in all other cells in the mouse) as the enzyme deleted only DCC in specific cells in the adult brain. Although the mice otherwise appear normal, testing their behavior revealed severe deficits in their ability to form certain types of new long-term memories.

— 1 year ago with 1 note
#memory  #neuroscience 
Newborn Neurons - Even in the Adult Aging Brain - Are Critical for Memory →

Newly generated neurons in the adult hippocampus are critical for memory retrieval, according to a new study. The functional role of newborn neurons in the brain is controversial, but the researchers report that memory retrieval was impaired when new neurons were silenced. The findings support the idea that the generation of new neurons in the brain may be crucial to normal learning and memory processes.

Previous research, by the study’s lead investigator Shaoyu Ge and others, has demonstrated that newborn neurons form connections with existing neurons in the adult brain. To help determine the role of newborn neurons, the researchers devised a new optogenetic technique to control newborn neurons and test their function in the hippocampus, one of the regions of the brain that generates new neurons, even in the adult aging brain.

“We believe that our study results provide strong support to the idea that new neurons are important for contextual fear memory and spatial navigation memory, two essential aspects of memory and learning that are modified by experience,” Ge said.

In the study, Ge and colleagues used a retroviral tool to deliver optogenes: genes that are engineered to express proteins that form channels responsive to light stimulation. Using their created opto-retrovirus, the research team labeled a cohort of newborn neurons that they could control with light illumination. By doing this, the team conducted an in-depth exploration of the circuit and behavioral functions of newborn neurons in the adult mouse brain. The researchers first determined when the neurons were “ready” in the hippocampus. Then they silenced the activity of neurons of different ages. They found that by silencing four-week-old neurons, an age known to be more responsive to change than existing neurons, but not older or younger neurons, memory retrieval was impaired in tasks known to depend on the functions of the hippocampus.

— 1 year ago
#memory  #neuroscience 
Scientists Discover a New Pathway that Regulates Memory Formation →

Scientists have identified a new pathway that appears to play a major role in information processing in the brain. Their research also offers insight into how imbalances in this pathway could contribute to cognitive abnormalities in humans. The study focuses on the actions of the histone deacetylase enzyme HDAC4. The researchers found that HDAC4 is critically involved in regulating genes essential for formation of synapses between neurons. “We found that HDAC4 represses these genes, and its function in a given neuron is controlled by activity of other neurons forming a circuit,” said Anton Maximov, senior investigator for the study.

Richard Sando III, a member of the Maximov lab and the first author of this study, noted the team become interested in class IIa histone deacetylases (HDACs), which include HDAC4, in part because they have been implicated in regulation of transcription of non-neuronal tissues. “Class IIa HDACs are also known to change their cellular localization in response to various signals,” he said. “There were hints that, in neurons, the translocation of HDAC4 from the nucleus to cytoplasm may be triggered by synaptic activity. We found that mutant mice lacking excitatory transmitter release in the brain accumulate HDAC4 in neuronal nuclei. But what was really exciting was our discovery that nuclear HDAC4 represses a pool of genes involved in synaptic communication and memory formation.”

To learn more about the function of HDAC4 in the brain, the team wanted to study its role in a mouse model. The team generated mice carrying a mutant form of HDAC4 that could not be exported from the cell nucleus. This mutant repressed transcription independently of neuronal activity. A human genetic study was published linking mutations in the human HDAC4 locus with a rare form of mental retardation. “One of these human mutations produces a protein similar to a mutant that we introduced into the mouse brain,” said Maximov. “Furthermore, our studies revealed that these mice do not learn and remember as well as normal mice, and their memory loss is associated with deficits in synaptic transmission. The pieces came together.”

The study indicates that although HDAC4 represses synapse formation when in a cell nucleus, it can be kept out of the nucleus as a result of signalling activity from adjacent neurons, and this allows formation of new synapses.

— 1 year ago with 2 notes
#neuroscience  #memory 
Brain-wave patterns mark loss of consciousness during anesthesia →

A new study reveals what happens inside the brain as patients lose consciousness during anesthesia. By monitoring brain activity as patients were given a common anesthetic, the researchers were able to identify a distinctive brain activity pattern that marked the loss of consciousness. This pattern, characterized by very slow oscillation, corresponds to a breakdown of communication between different brain regions, each of which experiences short bursts of activity interrupted by longer silences.

“Within a small area, things can look pretty normal, but because of this periodic silencing, everything gets interrupted every few hundred milliseconds, and that prevents any communication,” said Laura Lewis, one of the lead authors of a paper describing the findings.

For this study, the researchers used propofol, one of the most common anesthesia drugs. Propofol activates receptors found on neurons that are likely to make the neurons less active. The researchers studied epileptic patients, who had electrodes implanted in their brains to monitor their seizures and were undergoing surgery to have the electrodes removed. Loss of consciousness occurred within 40 seconds of propofol administration, and was defined by the moment when patients stopped responding to sounds that were played every four seconds.

Using two different-sized electrodes, the researchers were able to obtain two different readings of brain activity. The larger electrodes were spaced about a centimeter apart and recorded the overall EEG brain-wave pattern. Smaller electrodes, in an array 4 millimeters wide, were clustered in different regions and recorded from individual neurons. From the large electrodes the researchers observed that within a couple of seconds of losing consciousness, the brain EEG abruptly took on a pattern of low-frequency oscillation, about one cycle per second. At the same time, the electrodes recording from individual neurons revealed that within localized brain regions, neurons were active for a few hundred milliseconds, then shut off again for a few hundred milliseconds. This flickering of activity created the slow oscillation seen in the EEG. “When one area was active, it was likely that another brain area that it was trying to communicate with was not active. Even when the neurons were on, they still couldn’t send information to other brain regions,” Lewis said.

More:

General anaesthetic disrupts brain communication
Local calls only for anaesthetised brain
Brain fragments when you ‘go under’

— 1 year ago
#neuroscience  #consciousness 
How the brain and body communicate to regulate weight →

Humans maintain a healthy body weight through the process of energy balance, a tight matching between the number of calories consumed versus those expended. This balance results from a complex interchange of neurobiological crosstalk within regions of the brain’s hypothalamus, and when this “conversation” goes awry, obesity or anorexia can result. However, little is known about the details of this interchange. New research demonstrates how the GABA neurotransmitter selectively drives energy expenditure, and importantly, also help explain the neurocircuitry underlying the fat-burning properties of brown fat.

The hypothalamus is a region, under a centimeter in size, that directs a multitude of important functions in the body. It is the brain’s control center for energy balance, which results when the brain receives feedback signals from the body that communicate the status of fuel stores and then integrates this with input from the external world as well as a person’s emotional state to modify feeding behavior and energy expenditure.

The researchers investigated a population of neurons located at the base of the brain in the arcuate nucleus of the hypothalamus. “We genetically engineered mice such that they have a specific defect that prevents these neurons from releasing the inhibitory neurotransmitter, GABA,” says senior research author Bradford Lowell. “Mice with this defect developed marked obesity and, remarkably, their obesity was entirely due to a defect in burning off calories.” He added that food intake was entirely unaffected. By next engineering another group of mice in which these neurons could be selectively turned on at different times, the team showed that the arcuate neurons act through a series of downstream neurons to drive energy expenditure in brown fat. Recent studies have shown that brown fat, unlike energy-storing white fat, burns energy to generate heat in the process of thermogenesis.

"Energy expenditure mediated by brown adipose tissue is critical in maintaining body weight and prevents diet-induced obesity. Its brain-based regulatory mechanism, however, is still poorly understood," says first author Dong Kong. "Our discovery of a hypothalamus-based neurocircuit that ultimately controls thermogenesis is an important advance," Lowell adds. The investigators also found that when they turned on these neurons, energy expenditure was entirely dependent upon release of GABA. So release of GABA from arcuate neurons selectively drives energy expenditure.

— 1 year ago
#metabolism  #neuroscience 
Neuroscientists Find the Molecular “When” and “Where” of Memory Formation →

Neuroscientists have isolated the “when” and “where” of molecular activity that occurs in the formation of short-, intermediate-, and long-term memories. Research team leader Thomas Carew explained, “Memory formation is not simply a matter of turning molecules on and off; rather, it results from a complex temporal and spatial relationship of molecular interaction and movement.” Neuroscientists have previously uncovered different aspects of molecular signaling relevant to the formation of memories. But less understood is the spatial relationship between molecules and when they are active during this process.

The researchers studied the neurons in Aplysia californica, the California sea slug. It is a model organism well-suited for this type of research because its neurons are 10 to 50 times larger than those of higher organisms, such as vertebrates, and it possesses a relatively small network of neurons – characteristics that readily allow for the examination of molecular signaling during memory formation. Moreover, its coding mechanism for memories is highly conserved in evolution, and thus is similar to that of mammals.

The scientists focused on two molecules, MAPK and PKA, which earlier research has shown to be involved in many forms of memory and synaptic plasticity – that is, changes in the brain that occur after neuronal interaction. Less understood was how and where these molecules interacted. The researchers subjected the sea slugs to sensitization training, which induces increased behavioral reflex responsiveness following mild tail shock, or in this study, mild activation of the nerve form the tail. They then examined the subsequent molecular activity of both MAPK and PKA. Although both molecules are involved in the formation of memory for sensitization, the nature of their interaction is less clear.

What they found was MAPK and PKA coordinate their activity both spatially and temporally in memory formation. In the formation of intermediate-term (hours) and long-term (days) memories, both MAPK and PKA activity occur, with MAPK spurring PKA action. By contrast, for short-term memories (less than 30 minutes), only PKA is active, with no involvement of MAPK.

— 1 year ago with 3 notes
#neuroscience  #memory 
Sleeping brain behaves as if it's remembering something →

Researchers have measured, during sleep, the activity of brain regions involved in learning, memory, and Alzheimer’s disease. They discovered that one region – the entorhinal cortex – behaves as if it’s remembering something, even during anesthesia-induced sleep.

The research team simultaneously measured the activity of single neurons from parts of the brain involved in memory formation. In particular, the team looked at three connected brain regions in mice — the neocortex, the hippocampus, and the entorhinal cortex, which connects the other two regions. Previous studies have suggested that dialogue between the neocortex and the hippocampus during sleep was critical for memory formation, but researchers had not investigated the contribution of the entorhinal cortex to this conversation. The team found that the entorhinal cortex showed persistent activity, which is thought to mediate working memory while awake – for example, when people pay close attention to remember things temporarily.

Senior research author Mayank R Mehta and his team focused on the entorhinal cortex, which has many parts. The outer part mirrored the neocortical activity. However, the inner part behaved differently. When the neocortex became inactive, the neurons in the inner entorhinal cortex exhibited spontaneous persistent activity – they persisted in the active state, as if remembering something the neocortex had recently “said”. The team found that when the inner part of the entorhinal cortex became spontaneously persistent, it prompted the hippocampus neurons to become very active. On the other hand, when the neocortex was active, the hippocampus became quieter.

Current theories of brain communication during sleep posit that the hippocampus drives the neocortex. But the findings instead indicate that the entorhinal cortex is the third key actor in this dialogue and that the neocortex is driving the entorhinal cortex, which in turn behaves as if it is remembering something. That, in turn, drives the hippocampus. “This is a whole new way of thinking about memory consolidation theory,” Mehta said. “We found there is a new player involved in this process and it’s having an enormous impact. And what that third player is doing is being driven by the neocortex, not the hippocampus.”

— 1 year ago with 1 note
#memory  #neuroscience 
How attention helps you remember →

A new study adds knowledge about a neural circuit that makes us likelier to remember what we’re seeing when our brains are in a more attentive state. It was found that this circuit depends on astrocytes, a type of brain cell long thought to play only a supporting role in neural processing. When the brain is attentive, astrocytes relay messages alerting neurons of the visual cortex that they should respond strongly to whatever visual information they are receiving. The findings are the latest in a growing body of evidence suggesting that astrocytes are critically important for processing sensory information.

The researchers focused on what astrocytes do when the brain is stimulated to pay attention to a specific visual stimulus. When someone is paying close attention to something, the nucleus basalis — located deep within the brain, behind the eyes — floods the brain with the neurotransmitter acetylcholine. Some of this acetylcholine targets astrocytes in the visual cortex.

To explore how astrocytes react to this stimulation, the researchers measured what happened in the visual cortex as they showed mice several visual patterns. For one of the patterns, the researchers also provoked the nucleus basalis to release acetylcholine at the same time. This greatly boosted calcium levels in the astrocytes, indicating high activity. When the mice were shown the same stimuli a few minutes later, the pattern that had been presented along with acetylcholine stimulation provoked a much stronger response in neurons of the visual cortex than the other patterns. The researchers then did the same test in genetically engineered mice whose astrocytes were disabled. In those mice, the acetylcholine released by the nucleus basalis did not strengthen neurons’ response to visual stimuli.

“If you are paying attention to something, which causes this release of acetylcholine, that leads to a long-lasting memory of that stimulus. If you remove the astrocytes, that doesn’t happen,” senior research author Mriganka Sur says.

— 1 year ago with 1 note
#neuroscience  #astrocytes  #memory 
When Your Eyes Tell Your Hands What to Think →

Picking up your cup of morning coffee presents your brain with a set of complex decisions. You need to decide how to aim your hand, grasp the handle and raise the cup to your mouth, all without spilling the contents on your lap. A new study shows that, not only does your brain handle such complex decisions for you, it also hides information from you about how those decisions are made.

According to Yangqing ‘Lucie’ Xu, lead author of the study, “When you pick up an object, your brain automatically decides how to control your muscles based on what your eyes provide about the object’s shape. When you pick up a mug by the handle with your right hand, you need to add a clockwise twist to your grip to compensate for the extra weight that you see on the left side of the mug. We showed that the use of this visual information is so powerful and automatic that we cannot turn it off. When people see an object weighted in one direction, they actually can’t help but ‘feel’ the weight in that direction, even when they know that we’re tricking them.”

Steven Franconeri, co-author of the study, said the brain is constantly making decisions for us that we don’t know about or understand. “In this study’s example, your brain is automatically using visual information to tell your hands what they are feeling. We can show that these decisions are happening by manipulating the information your brain receives — we mirror-reverse the visual information and your brain now tells your hands that they are feeling the reverse of what they are actually feeling. This inference is mandatory — you feel it even if you know it’s not true. In the vast majority of cases, you want to ‘delegate’ decisions like this to the unconscious parts of your brain, leaving you free to focus on less straightforward problems.”

— 2 years ago with 10 notes
#neuroscience  #perception