Posts tagged synapses
Articles and news from the latest research reports.
When neurons have less to say, they say it with particular emphasis
The brain is an extremely adaptable organ – but it is also very conservative according to scientists from the Max Planck Institute of Neurobiology in Martinsried in collaboration with colleagues from the Friedrich Miescher Institute in Basel and the Ruhr Institute Bochum. The researchers succeeded in demonstrating that neurons in the brain regulate their own excitability so that the activity level in the network remains as constant as possible. Even in the event of major changes, for example the complete absence of information from a sensory organ, the almost silenced neurons re-establish levels of activity similar to their previous ones after only 48 hours. The mean activity level thus achieved is a basic prerequisite for a healthy brain and the formation of new connections between neurons – an essential capacity for regeneration following injury to the brain or a sensory organ, for example.
Neurons communicate using electrical signals. They transmit these signals to neighbouring cells via special contact points known as the synapses. When a new item of information presents for processing, the cells can develop new synaptic contacts with their neighbouring cells or strengthen existing ones. To enable forgetting, these processes are also reversible. The brain is consequently in a constant state of reorganisation, through which individual neurons are prevented from becoming either too active or too inactive. The aim is to keep the level of activity constant, as the long-term overexcitement of neurons can result in damage to the brain.
Too little activity is not good either. “The cells can only re-establish connections with their neighbours when they are ‘awake’, so to speak, that is when they display a minimum level of activity,” explains Mark Hübener, head of the recently published study. The international team of researchers succeeded in demonstrating for the first time that the brain itself compensates for massive changes in neuronal activity within a period of two days, and can return to a similar level of activity to that before the change.
Up to now, the only indication of this astonishing capacity of the brain came from cell cultures. It was also unclear as to how neurons could control their own excitability in relation to the activity of the entire network. Now, the scientists have made significant progress towards finding an answer to this question. In their study, they examined the visual cortex of mice that recently went blind. As expected, but never previously demonstrated, the activity of the neurons in this area of the brain did not fall to zero but to half of the original value. “That alone was an astonishing finding, as it shows the extent to which the visual cortex also processes information from other areas of the brain,” explains Tobias Bonhoeffer, who has been researching processes in the visual cortex at his department in the Max Planck Institute of Neurobiology for many years. “However, things really became exciting when we observed the area further over the following hours and days.”
The scientists were able, under the microscope, to witness “live” how the neurons in the visual cortex became active again. After just a few hours, they could clearly observe how the points of contact between the affected cells and neighbouring cells increased in size. When synapses get bigger, they also become stronger and signals are transmitted faster and more effectively. As a result of this intensification of the contact between the neurons, the activity of the affected network returned to its starting value after a period of between 24 and 48 hours. “To put it simply, due to the absence of visual input, the cells had less to say – but when they did say something, they said it with particular emphasis,” explains Mark Hübener.
Due to the simultaneous strengthening of all of the synapses of the affected neurons, major reductions in the neuronal activity can be normalised again with surprising speed. The relatively stable activity level thereby achieved is an essential prerequisite for maintaining a healthy, adaptable brain.
To live and learn: making memories has to be a speedy business
The brain is plastic - adapting to the hundreds of experiences in our daily lives by reorganizing pathways and making new connections between nerve cells. This plasticity requires that memories of new information and experiences are formed fast. So fast that the body has a special mechanism, unique to nerve cells, that enables memories to be made rapidly. In a new study from The Montreal Neurological Institute and Hospital, The Neuro, McGill University with colleagues at the Université de Montréal, researchers have discovered that nerve cells have a special ‘pre-assembly’ technique to expedite the manufacture of proteins at nerve cell connections (synapses), enabling the brain to rapidly form memories and be plastic.
Making a memory requires the production of proteins at synapses. These proteins then change the strength of the connection or pathway. In nerve cells the production process for memory proteins is already pre-assembled at the synapse but stalled just before completion, awaiting the proper signals to finish, thereby speeding up the entire process. When it comes time to making the memory, the process is switched on and the protein is made in a flash. The mechanism is analogous to a pre-fab home, or pre-made pancake batter that is assembled in advance and then quickly completed in the correct location at the correct time.
“It’s not only important to make proteins in the right place but, it’s also important not to make the protein when it’s the wrong time,” says Dr. Wayne Sossin, neuroscientist at The Neuro and senior investigator on the paper. “This is especially important with nerve cells in the brain, as you only want the brain to make precise connections. If this process is indiscriminate, it leads to neurological disease. This mechanism to control memory protein synthesis solves two problems: 1) how to make proteins only at the right time and 2) how to make proteins as quickly as possible in order to tightly associate the synaptic change with the experience/memory.
Making proteins from genetic material involves two major steps [a Nobel prize was awarded for the identification of the cell’s protein-making process]. In the first step, called transcription, the information in DNA that is stored and protected within the centre of the cell is copied to a messenger RNA (mRNA) – this copy is then moved to where it is needed in the cell. In the second step, called translation, the mRNA is used as a template of genetic information and ‘read’ by little machines called ribosomes, which decode the mRNA sequence and stitch together the correct amino acids to form the protein.
Dr. Sossin’s group at The Neuro has discovered that the mRNA travels to the synapse already attached to the ribosome, with the protein production process stopped just before completion of the product (at the elongation/termination step of translation, where amino acids are being assembled into protein). The ‘pre-assembly’ process then waits for synaptic signals before re-activating to produce a lot of proteins quickly in order to form a memory. “Our results reveal a new mechanism underlying translation-dependent synaptic plasticity, which is dysregulated in neurodevelopmental and psychiatric pathologies”, added Dr. Sossin. “Understanding the pathways involved may provide new therapeutic targets for neurodevelopmental disorders. “
(Source: mcgill.ca)
New Theory of Synapse Formation in the Brain
The human brain keeps changing throughout a person’s lifetime. New connections are continually created while synapses that are no longer in use degenerate. To date, little is known about the mechanisms behind these processes. Jülich neuroinformatician Dr. Markus Butz has now been able to ascribe the formation of new neural networks in the visual cortex to a simple homeostatic rule that is also the basis of many other self-regulating processes in nature. With this explanation, he and his colleague Dr. Arjen van Ooyen from Amsterdam also provide a new theory on the plasticity of the brain – and a novel approach to understanding learning processes and treating brain injuries and diseases.
The brains of adult humans are by no means hard wired. Scientists have repeatedly established this fact over the last few years using different imaging techniques. This so-called neuroplasticity not only plays a key role in learning processes, it also enables the brain to recover from injuries and compensate for the loss of functions. Researchers only recently found out that even in the adult brain, not only do existing synapses adapt to new circumstances, but new connections are constantly formed and reorganized. However, it was not yet known how these natural rearrangement processes are controlled in the brain. In the open-access journal PLOS Computational Biology, Butz and van Ooyen now present a simple rule that explains how these new networks of neurons are formed.
"It’s very likely that the structural plasticity of the brain is the basis for long-term memory formation," says Markus Butz, who has been working at the recently established Simulation Laboratory Neuroscience at the Jülich Supercomputing Centre for the past few months. "And it’s not just about learning. Following the amputation of extremities, brain injury, the onset of neurodegenerative diseases, and strokes, huge numbers of new synapses are formed in order to adapt the brain to the lasting changes in the patterns of incoming stimuli."
Activity regulates synapse formation
Τhese results show that the formation of new synapses is driven by the tendency of neurons to maintain a ‘pre-set’ electrical activity level. If the average electric activity falls below a certain threshold, the neurons begin to actively build new contact points. These are the basis for new synapses that deliver additional input – the neuron firing rate increases. This also works the other way round: as soon as the activity level exceeds an upper limit, the number of synaptic connections is reduced to prevent any overexcitation – the neuron firing rate falls. Similar forms of homeostasis frequently occur in nature, for example in the regulation of body temperature and blood sugar levels.
However, Markus Butz stresses that this does not work without a certain minimal excitation of the neurons: “A neuron that no longer receives any stimuli loses even more synapses and will die off after some time. We must take this restriction into account if we want the results of our simulations to agree with observations.” Using the visual cortex as an example, the neuroscientists have studied the principles according to which neurons form new connections and abandon existing synapses. In this region of the brain, about 10% of the synapses are continuously regenerated. When the retina is damaged, this percentage increases even further. Using computer simulations, the authors succeeded in reconstructing the reorganization of the neurons in a way that conforms to experimental results from the visual cortex of mice and monkeys with damaged retinas.
The visual cortex is particularly suitable for demonstrating the new growth rule, because it has a property referred to as retinotopy: This means that points projected beside each other onto the retina are also arranged beside each other when they are projected onto the visual cortex, just like on a map. If areas of the retina are damaged, the cells onto which the associated images are projected receive different inputs. “In our simulations, you can see that areas which no longer receive any input from the retina start to build crosslinks, which allow them to receive more signals from their neighbouring cells,” says Markus Butz. These crosslinks are formed slowly from the edge of the damaged area towards the centre, in a process resembling the healing of a wound, until the original activity level is more or less restored.
Synaptic and structural plasticity
"The new growth rule provides structural plasticity with a principle that is almost as simple as that of synaptic plasticity," says co-author Arjen van Ooyen, who has been working on models for the development of neural networks for decades. As early as 1949, psychology professor Donald Olding Hebb discovered that connections between neurons that are frequently activated will become stronger. Those that exchange little information will become weaker. Today, many scientists believe that this Hebbian principle plays a central role in learning and memory processes. While synaptic plasticity in involved primarily in short-term processes that take from a few milliseconds to several hours, structural plasticity extends over longer time scales, from several days to months.
Structural plasticity therefore plays a particularly important part during the (early) rehabilitation phase of patients affected by neurological diseases, which also lasts for weeks and months. The vision driving the project is that valuable ideas for the treatment of stroke patients could result from accurate predictions of synapse formation. If doctors knew how the brain structure of a patient will change and reorganize during treatment, they could determine the ideal times for phases of stimulation and rest, thus improving treatment efficiency.
New approach for numerous applications
"It was previously assumed that structural plasticity also follows the principle of Hebbian plasticity. The findings suggest that structural plasticity is governed by the homeostatic principle instead, which was not taken into consideration before," says Prof. Abigail Morrison, head of the Simulation Laboratory Neuroscience at Jülich. Her team is already integrating the new rule into the freely accessible simulation software NEST, which is used by numerous scientists worldwide.
These findings are also of relevance for the Human Brain Project. Neuroscientists, medical scientists, computer scientists, physicists, and mathematicians in Europe are working hand in hand to simulate the entire human brain on high-performance computers of the next generation in order to better understand how it functions. “Due to the complex synaptic circuitry in the human brain, it’s not plausible that its fault tolerance and flexibility are achieved based on static connection rules. Models are therefore required for a self-organization process,” says Prof. Markus Diesmann from Jülich’s Institute of Neuroscience and Medicine, who is involved in the project. He heads Computational and Systems Neuroscience (INM-6), a subinstitute working at the interface between neuroscientific research and simulation technology.
Nobel Prize winner reports new model for neurotransmitter release
In a Neuron article published online October 10th, recent Nobel Laureate Thomas C. Südhof challenges long-standing ideas on how neurotransmitter gets released at neuronal synapses. On October 7th, Südhof won the Nobel Prize in Physiology or Medicine, alongside James Rothman and Randy Schekman, for related work on how vesicles—such as those in neurons that contain neurotransmitter—are transported within cells.
Neurotransmitter-containing vesicles are found inside neurons very close to the end of the axon. Here, they can quickly fuse with the neuronal membrane surrounding the axon to spill their contents into the synapse. How these vesicles are able to fuse with the membrane has been controversial, however, and understanding this process would give researchers much greater insight how neurons communicate with each other. Previously, it was thought that proteins found on the outside of the vesicles and on the axon membrane (called SNARE proteins) would come together and physically form a pore through which the contents of the vesicle—the neurotransmitter—could be released into the synapse. Now, the new findings from Südhof suggest that these proteins may not form a pore at all. Instead, their main role may be to physically force the vesicle and the axon membrane to get very close to each other; once they are forced into contact, the two appear able to fuse spontaneously.
"The importance of SNARE transmembrane regions has never been tested in a physiological fusion reaction," says Dr. Südhof. "We show that the SNARE transmembrane regions are dispensible for fusion as such but are important for maintaining the normal efficiency of regulated fusion. These findings rule out an essential participation of the SNARE transmembrane regions in fusion and are consistent with the notion that the SNAREs function in fusion as force generators, i.e., that their function is to force the membranes close together." The results are controversial due to years of research supporting the SNARE-protein pore hypothesis. These provocative findings could change long-held models for how neurotransmitters are released from neurons and suggest that there remain many open questions about the role of SNAREs in neurotransmitter release at synapses.
(Image: This is a molecular model of the active zone protein complex and its relation to the synaptic vesicle fusion machinery, Ca2+ channels, and synaptic cell-adhesion molecules. Credit: Neuron, Volume 75, Issue 1, 11-25, 12 July 2012, Sudhof)
Made to Order at the Synapse: Dynamics of Protein Synthesis at Neuron Tip is Basis for Memory and Learning
Understanding RNA biology in dendrites may inform neurological and psychiatric illness therapeutics
Protein synthesis in the extensions of nerve cells, called dendrites, underlies long-term memory formation in the brain, among other functions. “Thousands of messenger RNAs reside in dendrites, yet the dynamics of how multiple dendrite messenger RNAs translate into their final proteins remain elusive,” says James Eberwine, PhD, professor of Pharmacology, Perelman School of Medicine at the University of Pennsylvania, and co-director of the Penn Genome Frontiers Institute.
Dendrites, which branch from the cell body of the neuron, play a key role in the communication between cells of the nervous system, allowing for many neurons to connect with each other. Dendrites detect the electrical and chemical signals transmitted to the neuron by the axons of other neurons. The synapse is the neuronal structure where this chemical connection is formed, and investigators surmise that it is here where learning and memory occur.
These structural and chemical changes – called synaptic plasticity — require rapid, new synthesis of proteins. Cells may use different rates of translation in different types of mRNA to produce the right amounts and ratios of required proteins.
Knowing how proteins are made to order – as it were - at the synapse can help researchers better understand how memories are made. Nevertheless, the role of this “local” environment in regulating which messenger RNAs are translated into proteins in a neuron’s periphery is still a mystery.
Eberwine, first author Tae Kyung Kim, PhD, a postdoc in the Eberwine lab, and colleagues including Jai Yoon Sul, PhD, assistant professor in Pharmacology, showed that protein translation of two dendrite mRNAs is complex in space and time, as reported online in Cell Reports this week.
“We needed to look at more than one RNA at the same time to get a better handle on real- world processes, and this is the first study to do that in a live neuron,” Eberwine explains.
At Home in the Hippocampus
“It’s not always one particular RNA that dominates at a translation hotspot versus another type of RNA,” says Eberwine. “Since there are 1,000 to 3,000 different mRNA types present in the dendrite overall, but not 1,000 to 3,000 different translational hot spots, do the mRNAs ‘take turns’ being translated in space and time at the ribosomes at the hotspots?”
The researchers engineered the glutamate receptor RNAs to contain different fluorescent proteins that are independently detectable, as well as a photo-switchable protein to determine when new proteins were being made. In the case of the photo-switchable protein studies, when an mRNA for the glutamate receptor protein is marked green, it means it has already been translated.
When a laser is passed over the green protein, it changes to red as a way of tagging when it has been been translated, and new proteins synthesized at that hotspot would be green, which is visible by the appearance of yellow fluorescence (green + red, as measured by light on the visible spectrum). These tricks of the light allow the team to keep track of newly made proteins over time and space.
“This is the first time this method of protein labeling has been used to measure the act of translation of multiple proteins over space and time in a quantitative way,” says Eberwine. “We call it quantitative functional genomics of live cell translation.”
“Our results suggest that the location of the translational hotspot is a regulator of the simultaneous translation of multiple messenger RNAs in nerve cell dendrites and therefore synaptic plasticity,” says Sul.
Laying the Groundwork
Almost 10 years ago, the Eberwine lab discovered that nerve-cell dendrites have the capacity to splice messenger RNA, a process once believed to take place only in the nucleus of cells. Here, a gene is copied into mRNA, which possesses both exons (mature mRNA regions that code for proteins) and introns (non-coding regions). mRNA splicing works by cutting out introns and merging the remaining exon pieces, resulting in an mRNA capable of being translated into a specific protein.
The vast array of proteins within the human body arises in part from the many ways that mRNAs can be spliced and reconnected. Specifically, splicing removes pieces of intron and exon regions from the RNA. The resulting spliced RNA is made into protein.
If the RNA has different exons spliced in and out of it, then different proteins can be made from this RNA. The Eberwine lab was successful in showing that splicing can occur in dendrites because they used sensitive technologies developed in their lab, which permits them to detect and quantify RNA splicing, as well as the translated protein in single isolated dendrites.
Understanding the dynamics of RNA biology and protein translation in dendrites promises to provide insight into regulatory mechanisms that may be modulated for therapeutic purposes in neurological and psychiatric illnesses. The directed development of therapeutics requires this detailed knowledge, says Eberwine.
Virginia Tech to Host Neuroscience Workshop in Switzerland
Neuroscientists will discuss cognition, computation, decisions
Nearly two dozen of the world’s leading neuroscientists will gather in Switzerland next month to share their latest findings on the mysteries of how the brain processes information and makes decisions.
The Virginia Tech Carilion Research Institute European–U.S. Workshop on the Neuroscience of Cognition, Computation, and Decisions will be held at Virginia Tech’s Center for European Studies and Architecture at Riva San Vitale in Ticino on Oct. 16 to Oct. 18.
“We have two principal goals for this intensive workshop,” said Michael Friedlander, associate provost for health sciences at Virginia Tech and executive director of the Virginia Tech Carilion Research Institute. “First, we want to identify new and powerful integrated approaches to bridge multiple levels of understanding brain function. We are also hoping to lay the foundations for pioneering innovative and disruptive approaches to transcending disciplines and technologies across teams of leading European brain researchers and Virginia Tech Carilion Research Institute neuroscientists.”
The workshop will convene 10 neuroscientists from the institute and 13 neuroscientists from prominent brain-research institutions in five European countries, includinbg the Centre National de la Recherche Scientifique and École Polytechnique in France; the Central Institute of Mental Health Mannheim, Freie Universität Berlin, the Max Planck Institute for Biological Cybernetics, the Max Planck Institute for Human Development, and the University of Heidelberg in Germany; the International School for Advanced Studies in Trieste, Italy; École Polytechnique Fédérale de Lausanne, ETH Zürich, and the University of Zurich in Switzerland; and University College London in the United Kingdom.
Workshop participants will address emerging views of how neuronal and synaptic networks in the brain assemble, process, store, and access information and how large-scale networks of interconnected neurons perform in humans and other mammals. The participants will also consider the functional architecture that underlies the brain’s decision-making capacity, the neural basis of social interactions, the effects of the environment on information processing, and the consequences of a range of disorders on the function of the human brain.
Participants will share their newest discoveries in multiple sessions of several speakers each, followed by in-depth discussions to identify congruent perspectives and converging insights from multiple disciplines.
The discoveries will represent a broad array of technological and conceptual approaches, including analysis of detailed structural and functional properties of individual neurons and synaptic networks obtained with powerful electrophysiological, genetic, and optical imaging methods; functional brain imaging and behavioral studies in individuals and groups of interacting humans; and computational analysis and modeling of brain function and behavior.
Additional experts will address economics and game theory applications to human brain function and behavior in health and in disease; analysis of development, aging, and educational interventions on brain function; and the modulation of brain function acutely and over time in health and in various disorders that affect behavior, neural information processing, and decision-making.
“This workshop is taking place at a confluence of important national and international milestones in brain research in both Europe and the United States,” Friedlander said. “The Blue Brain Project in Europe represents a major international coalition to support large-scale, detailed analysis of the circuitry of the brain, while in the United States, President Barack Obama’s BRAIN Initiative will support innovative new approaches to high-resolution, large-scale functional mapping of the brain. We’re hoping to harness the wisdom of experts on both continents to develop new approaches and better technologies for diagnosing and treating neurological and psychiatric disorders that affect people worldwide.”
Building the best brain: U-M researchers show how brain cell connections get cemented early in life
Research on synapse stabilization could aid understanding of autism, schizophrenia, intellectual disability
When we’re born, our brains aren’t very organized. Every brain cell talks to lots of other nearby cells, sending and receiving signals across connections called synapses.
But as we grow and learn, things get a bit more stable. The brain pathways that will serve us our whole lives start to organize, and less-active, inefficient synapses shut down.
But why and how does this happen? And what happens when it doesn’t go normally? New research from the University of Michigan Medical School may help explain.
In a new paper in Nature Neuroscience, a team of U-M neuroscientists reports important findings about how brain cells called neurons keep their most active connections with other cells, while letting other synapses lapse.
Specifically, they show that SIRP alpha, a protein found on the surface of various cells throughout the body, appears to play a key role in the process of cementing the most active synaptic connections between brain cells. The research, done in mouse brains, was funded by the National Institutes of Health and several foundations.
The findings boost understanding of basic brain development – and may aid research on conditions like autism, schizophrenia, epilepsy and intellectual disability, all of which have some basis in abnormal synapse function.
“For the brain to be really functional, we need to keep the most active and most efficient connections,” says senior author Hisashi Umemori, M.D., Ph.D., a research assistant professor at U-M’s Molecular and Behavioral Neuroscience Institute and assistant professor of biological chemistry in the Medical School. “So, during development it’s crucial to establish efficient connections, and to eliminate inactive ones. We have identified a key molecular mechanism that the brain uses to stabilize and maturate the most active connections.”
Umemori says the new findings on SIRP alpha grew directly out of previous work on competition between neurons, which enables the most active ones to become part of pathways and circuits. (Read more on this research)
The team suspected that there must be some sort of signal between the two cells on either side of each synapse — something that causes the most active synapses to stabilize. So they set out to find out what it was.
SIRP-rise findings
The group had previously shown that SIRP-alpha was involved in some way in a neuron’s ability to form a presynaptic nerve terminal – an extension of the cell that reaches out toward a neighboring cell, and can send the chemical signals that brain cells use to talk to one another.
SIRP-alpha is also already known to serve an important function in the rest of the body – essentially, helping normal cells tell the immune system not to attack them. It may also help cancer cells evade detection by the immune system’s watchdogs.
In the new study, the team studied SIRP alpha function in the brain – and started to understand its role in synapse stabilization. They focused on the hippocampus, a region of the brain very important to learning and memory.
Through a range of experiments, they showed that when a brain cell receives signals from a neighboring cell across a synapse, it actually releases SIRP-alpha into the space between the cells. It does this through the action of molecules inside the cell – called CaMK and MMP – that act like molecular scissors, cutting a SIRP-alpha protein in half so that it can float freely away from the cell.
The part of the SIRP-alpha protein that floats into the synapse “gap” latches on to a receptor on the other side, called a CD47 receptor. This binding, in turn, appears to tell the cell that the signal it sent earlier was indeed received – and that the synapse is a good one. So, the cell brings more chemical signaling molecules down that way, and releases them into the synapse.
As more and more nerve messages travel between the “sending” and “receiving” cells on either side of that synapse, more SIRP-alpha gets cleaved, released into the synapse, and bound to CD47.
The researchers believe this repeated process is what helps the cells determine which synapses to keep – and which to let wither.
Umemori says the team next wants to look at what happens when SIRP-alpha doesn’t get cleaved as it should – and at what’s happening in cells when a synapse gets eliminated.
“This step of shedding SIRP-alpha must be critical to developing a functional neural network,” he says. “And if it’s not done well, disease or disorders may result. Perhaps we can use this knowledge to treat diseases caused by defects in synapse formation.”
He notes that the gene for the CD47 receptor is found in the same general area of our DNA as several genes that are suspected to be involved in schizophrenia.
Nanoscale neuronal activity measured for the first time
A new technique that allows scientists to measure the electrical activity in the communication junctions of the nervous systems has been developed by a researcher at Queen Mary University of London.
The junctions in the central nervous systems that enable the information to flow between neurons, known as synapses, are around 100 times smaller than the width of a human hair (one micrometer and less) and as such are difficult to target let alone measure.
By applying a high-resolution scanning probe microscopy that allows three-dimensional visualisation of the structures, the team were able to measure and record the flow of current in small synaptic terminals for the first time.
“We replaced the conventional low-resolution optical system with a high-resolution microscope based on a nanopipette,” said Dr Pavel Novak, a bioengineering specialist from Queen Mary’s School of Engineering and Materials Science.
“The nanopipette hovers above the surface of the sample and scans the structure to reveal its three-dimensional topography. The same nanopipette then attaches to the surface at selected locations on the structure to record electrical activity. By repeating the same procedure for different locations of the neuronal network we can obtain a three-dimensional map of its electrical properties and activity.”
The research, published (Wednesday 18 September) in Neuron, opens a new window into the neuronal activity at nanometre scale, and may contribute to the wider effort of understanding the function of the brain represented by the Brain Activity Map Project (BRAIN initiative), which aims to map the function of each individual neuron in the human brain.
(Source: qmul.ac.uk)
Newly Discovered ‘Switch’ Plays Dual Role In Memory Formation
Researchers at Johns Hopkins have uncovered a protein switch that can either increase or decrease memory-building activity in brain cells, depending on the signals it detects. Its dual role means the protein is key to understanding the complex network of signals that shapes our brain’s circuitry, the researchers say. A description of their discovery appears in the July 31 issue of the Journal of Neuroscience.
“What’s interesting about this protein, AGAP3, is that it is effectively double-sided: One side beefs up synapses in response to brain activity, while the other side helps bring synapse-building back down to the brain’s resting state,” says Richard Huganir, Ph.D., a professor and director of the Solomon H. Snyder Department of Neuroscience at the Johns Hopkins University School of Medicine and co-director of the Brain Science Institute at Johns Hopkins. “The fact that it links these two opposing activities indicates AGAP3 may turn out to be central to controlling the strength of synapses.”
Huganir has long studied how connections between brain cells, known as synapses, are strengthened and weakened to form or erase memories. The new discovery came about when he and postdoctoral fellow Yuko Oku, Ph.D., investigated the chain reaction of signals involved in one type of synaptic strengthening.
In a study of the proteins that interact with one of the known proteins from that chain reaction, the previously unknown AGAP3 turned up. It contained not only a site designed to bind another protein involved in the chain reaction that leads from brain stimulation to learning, but also a second site involved in bringing synapse-building activity down to normal levels after a burst of activity.
Although it might seem the two different functions are behaving at cross-purposes, Oku says, it also could be that nature’s bundling of these functions together in a single protein is an elegant way of enabling learning and memory while preventing dangerous overstimulation. More research is needed, Oku says, to figure out whether AGAP3’s two sites coordinate by affecting each other’s activity, or are effectively free agents.
New clue on the origin of Huntington’s disease
The synapses in the brain act as key communication points between approximately one hundred billion neurons. They form a complex network connecting various centres in the brain through electrical impulses.
New research from Lund University suggests that it is precisely here, in the synapses, that Huntington’s disease might begin.
The researchers looked into the brains of mice with real-time imaging methods, following some of the very first stages of the disease through advanced microscopes. What they discovered was an unprecedented degradation of synaptic activity. Long before the well documented nerve cell death, synapses that are important for communication between brain centres that control memory and learning begin to wither. This process has never been mapped before and could be an important step towards understanding the serious non-motor symptoms that affect Huntington patients long before the movement disorders start to show.
“With the naked eye, we have now been able to follow the step by step events when these synapses start to break down. If we are to halt or reverse this process in the future, it is necessary to understand exactly what happens in the initial phase of the disease. Now we know more”, says Professor Jia-Yi Li, the research group leader.
Huntington’s disease has long been characterized by the involuntary writhing movements faced by patients. But in fact, Huntington’s has a very broad and highly individual symptomatology. Depression, memory loss and sleep disorders are all common early on in the disease.
“Many patients testify that these symptoms affect quality of life significantly more than the involuntary jerky movements. Therefore, it is extremely important that we achieve progress in this field of research. Our goal now is to find new therapies that can increase the lifespan of these synapses and maintain their vital function”, explains postdoc Reena, who lead the imaging experiments.
(Source: lunduniversity.lu.se)