Posts Tagged Spine

[WEB SITE] Neuroscientists unravel how two different types of brain plasticity work on synapses

 

The brain’s crucial function is to allow organisms to learn and adapt to their surroundings. It does this by literally changing the connections, or synapses, between neurons, strengthening meaningful patterns of neural activity in order to store information. The existence of this process – brain plasticity – has been known for some time.

But actually, there are two different types of brain plasticity at work on synapses. One is “Hebbian plasticity”; it is the one which effectively allows for the recording of information in the synapses, named after pioneering neuroscientist Donald Hebb. The other, more recently discovered, is “homeostatic synaptic plasticity” (HSP), and, like other “homeostatic” processes in the body such as maintaining a constant body temperature, its purpose is to keep things stable. In this case, HSP ensures that the brain doesn’t build up too much activity (as is the case in epilepsy) or become too quiet (as can happen when you lose synapses in Alzheimer’s Disease).

However, little is known about how these two types of plasticity actually interact in the brain. Now, a team of neuroscientists at the Champalimaud Centre for the Unknown, in Lisbon, Portugal, has begun to unravel the fundamental processes that happen in the synapse when the two mechanisms overlap. Their results were published in the journal iScience.

“In theory, the two types of plasticity act as opposing forces”, says Anna Hobbiss, first author of the new study, which was led by Inbal Israely. “Hebbian plasticity reacts to activity at the synapses by inciting them to get stronger while HSP reacts to it by making them weaker. We wanted to understand, on a cellular and molecular level, how the synapse deals with these two forces when they are present at the same time.”

In so doing, the authors have surprisingly shown that, contrary to what might be expected, HSP facilitates Hebbian plasticity, and thus influences memory formation and learning. This means that these two types of plasticity “may actually not be such distinct processes, but instead work together at the same synapses”, says Israely.

The team’s goal was to determine the changes in size of minute structures called dendritic spines, which are the “receiving end” of the synapse. The size of these spines changes to reflect the strength of the synaptic connection.

For this, they studied cells from the mouse hippocampus, a part of the brain which is crucial for learning. In their experiments, they blocked activity in the cells by introducing a potent neurotoxin called tetrodotoxin, thus simulating the loss of input to a certain part of the brain (“think about a person suddenly becoming blind, which leads to loss of input from the eyes to the brain”, says Hobbiss).

Forty eight hours later, they mimicked a small recovery of activity at only one synapse by releasing a few molecules of a neurotransmitter called glutamate on single spines of single neurons. This was possible thanks to a very high resolution, state-of-the-art laser technology, called two-photon microscopy, which allowed the scientists to very precisely visualize and target individual dendritic spines.

As this process evolved, the team closely watched what was happening to the spines – and they saw various anatomical changes. First, the silencing of all neural activity made the spines grow in size. “The spines are like little microphones, which, when there is silence, ramp up the ‘volume’ to try and catch even the faintest noise”, Hobbiss explains.

The scientists then activated individual spines with pulses of glutamate and watched them for two hours. One of the things they thought could happen was that the size of the spines would not grow further, since they had already turned up their ‘volume’ as far is it would go. But the opposite happened: the spines grew even more, with the smaller spines showing the biggest growth.

Finally, the authors also saw growth in neighboring spines, even though the experiment only targeted one spine. “We found that after a lack of activity, other spines in the vicinity also grew, further enhancing the cell’s sensitivity to restored neural transmission”, says Hobbiss. “The cells become more sensitive, more susceptible to encode information. It is as though the ‘gain’ has been turned up”, she adds.

“The fact that neighboring spines grew together with an active spine signifies that homeostatic plasticity changes one of the hallmark features of information storage, which is that plasticity is limited to the site of information entry”, Israely explains. “So, in this sense, the different plasticity mechanisms which are at work in the neuron can cooperate to change which and how many inputs respond to a stimulus. I think this is an exciting finding of our study.”

Taken together, these results show that homeostatic plasticity can actually rev up Hebbian plasticity, the type required for storing information. “Our work adds a piece to the puzzle of how the brain performs one of its fundamental tasks: being able to encode information while still keeping a stable level of activity”, concludes Hobbiss.

The misregulation of homeostatic plasticity – the stabilizing one – has started to be implicated in human health, specifically neurodevelopmental disorders such as Fragile X syndrome and Rett syndrome as well as neurodegenerative ones such as Alzheimer’s Disease. “Perhaps this balance is what allows us to be able to learn new information while retaining stability of that knowledge over a lifetime”, says Israely.

 

via Neuroscientists unravel how two different types of brain plasticity work on synapses

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[WEB SITE] Study uncovers genetic trigger that may help the brain to recover from stroke, other injuries

Scientists have found a genetic trigger that may improve the brain’s ability to heal from a range of debilitating conditions, from strokes to concussions and spinal cord injuries.

A new study in mice from UT Southwestern’s O’Donnell Brain Institute shows that turning on a gene inside cells called astrocytes results in a smaller scar and – potentially – a more effective recovery from injury.

The research examined spinal injuries but likely has implications for treating a number of brain conditions through gene therapy targeting astrocytes, said Dr. Mark Goldberg, Chairman of Neurology & Neurotherapeutics at UT Southwestern.

“We’ve known that astrocytes can help the brain and spinal cord recover from injury, but we didn’t fully understand the trigger that activates these cells,” Dr. Goldberg said. “Now we’ll be able to look at whether turning on the switch we identified can help in the healing process.”

The study published in Cell Reports found that the LZK gene of astrocytes can be turned on to prompt a recovery response called astrogliosis, in which these star-shaped cells proliferate around injured neurons and form a scar.

Scientists deleted the LZK gene in astrocytes of one group of injured mice, which decreased the cells’ injury response and resulted in a larger wound on the spinal cord. They overexpressed the gene in other injured mice, which stimulated the cells’ injury response and resulted in a smaller scar. Overexpressing the gene in uninjured mice also activated the astrocytes, confirming LZK as a trigger for astrogliosis.

Dr. Goldberg said a smaller scar likely aids the healing process by isolating the injured neurons, similar to how isolating a spreading infection can improve recovery. “But we don’t know under what circumstances this hypothesis is true because until now we didn’t have an easy way to turn the astrocyte reactivity on and off,” he said.

Further study is needed to analyze whether a compact scar tissue indeed improves recovery and how this process affects the neurons’ ability to reform connections with each other.

Dr. Goldberg’s lab will conduct more research to examine the effects of astrogliosis in stroke and spinal cord injuries. The researchers will determine whether turning up LZK in mice in advance of an injury affects its severity. They will then measure how the formation of the compact scar helps or hinders recovery.

“It has been a big mystery whether increasing astrocyte reactivity would be beneficial,” said Dr. Meifan Amy Chen, the study’s lead author and Instructor of Neurology at the Peter O’Donnell Jr. Brain Institute. “The discovery of LZK as an on switch now offers a molecular tool to answer this question.”

 

via Study uncovers genetic trigger that may help the brain to recover from stroke, other injuries

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[WEB SITE] New wearable electronic device could revolutionise treatment for stroke patients

Stroke patients are starting a trial of a new electronic device to recover movement and control of their hand.

Neuroscientists at Newcastle University have developed the device, the size of a mobile phone, which delivers a series of small electrical shocks followed by an audible click to strengthen brain and spinal connections.

The experts believe this could revolutionise treatment for patients, providing a wearable solution to the effects of stroke.

Following successful work in primates and healthy human subjects, the Newcastle University team are now working with colleagues at the prestigious Institute of Neurosciences, Kolkata, India, to start the clinical trial. Involving 150 stroke patients, the aim of the study is to see whether it leads to improved hand and arm control.

Stuart Baker, Professor of Movement Neuroscience at Newcastle University who has led the work said: “We were astonished to find that a small electric shock and the sound of a click had the potential to change the brain’s connections. However, our previous research in primates changed our thinking about how we could activate these pathways, leading to our study in humans.”

Recovering hand control

Publishing today in the Journal of Neuroscience, the team report on the development of the miniaturised device and its success in healthy patients at strengthening connections in the reticulospinal tract, one of the signal pathways between the brain and spinal cord.

This is important for patients as when people have a stroke they often lose the major pathway found in all mammals connecting the brain to spinal cord. The team’s previous work in primates showed that after a stroke they can adapt and use a different, more primitive pathway, the reticulospinal tract, to recover.

However, their recovery tends to be imbalanced with more connections made to flexors, the muscles that close the hand, than extensors, those that open the hand. This imbalance is also seen in stroke patients as typically, even after a period of recuperation, they find that they still have weakness of the extensor muscles preventing them opening their fist which leads to the distinctive curled hand.

Partial paralysis of the arms, typically on just one side, is common after stroke, and can affect someone’s ability to wash, dress or feed themselves. Only about 15% of stroke patients spontaneously recover the use of their hand and arm, with many people left facing the rest of their lives with a severe level of disability.

Senior author of the paper, Professor Baker added: “We have developed a miniaturised device which delivers an audible click followed by a weak electric shock to the arm muscle to strengthen the brain’s connections. This means the stroke patients in the trial are wearing an earpiece and a pad on the arm, each linked by wires to the device so that the click and shock can be continually delivered to them.

“We think that if they wear this for 4 hours a day we will be able to see a permanent improvement in their extensor muscle connections which will help them gain control on their hand.”

Improving connections

The techniques to strengthen brain connections using paired stimuli are well documented, but until now this has needed bulky equipment, with a mains electric supply.

The research published today is a proof of concept in human subjects and comes directly out of the team’s work on primates. In the paper they report how they pair a click in a headphone with an electric shock to a muscle to induce the changes in connections either strengthening or weakening reflexes depending on the sequence selected. They demonstrated that wearing the portable electronic device for seven hours strengthened the signal pathway in more than half of the subjects (15 out of 25).

Professor Stuart Baker added: “We would never have thought of using audible clicks unless we had the recordings from primates to show us that this might work. Furthermore, it is our earlier work in primates which shows that the connections we are changing are definitely involved in stroke recovery.”

The work has been funded through a Milstein Award from the Medical Research Council and the Wellcome Trust.

The clinical trial is just starting at the Institute of Neurosciences, Kolkata, India. The country has a higher rate of stroke than Western countries which can affect people at a younger age meaning there is a large number of patients. The Institute has strong collaborative links with Newcastle University enabling a carefully controlled clinical trial with results expected at the end of this year.

A patient’s perspective

Chris Blower, 30, is a third year Biomedical Sciences student at Newcastle University and he had a stroke when he was a child after open heart surgery. He describes his thoughts on the research:

I had a stroke at the age of seven. The immediate effect was paralysis of the right-hand side of my body, which caused slurred speech, loss of bowel control and an inability to move unaided. Though I have recovered from these immediate effects, I am now feeling the longer term effects of stroke; slow, limited and difficult movement of my right arm and leg.

My situation is not unique and many stroke survivors have similar long-term effects to mine. Professor Baker’s work may be able to help people in my position regain some, if not all, motor control of their arm and hand. His research shows that, in stroke, the brains motor pathway to the spinal cord is damaged and that an evolutionarily older signal pathway could be ‘piggybacked’ and used instead. With electrical stimulation, exercise and an audible cue the brain can be taught to use this older pathway instead.

This gives me a lot of hope for stroke survivors. My wrist and fingers pull in, closing my hand into a fist, but with the device Professor Baker is proposing my brain could be re-taught to use my muscles and pull back, opening my hand out. The options presented to me so far, by doctors, have been Botox injections and surgery; Botox in my arm would weaken the muscles closing my hand and allow my fingers to spread, surgery would do the same thing by moving the tendons in my arm. Professor Baker’s electrical stimulations is certainly a more appealing option, to me, as it seems to be a permanent solution that would not require an operation on my arm.

I was invited to look around the animal house and observe a macaque monkey undergoing a test and this has made me think about my own stroke and the effect it has had on my life.

I have never seen anything like this before and I didn’t know what to expect. The macaque monkey that I observed was calmly carrying out finger manipulation tests while electrodes monitored the cells of her spinal cord.

Although this procedure requires electrodes to be placed into the brain and spine of the animal, Professor Baker explained how the monkey had been practicing and learning this test for two years before the monitoring equipment was attached. In this way the testing has become routine before it had even started and the animal was in no pain or distress, even at the sight of a stranger (me).

The animals’ calm, placid temperaments carry over to their living spaces; with lots of windows, natural light and high up spaces the macaques are able to see all around them and along the corridors. This means that they aren’t feeling threatened when people approach and are comfortable enough that even a stranger (me, again) can approach and say ‘hello’.

From my tour of the animal house at the Institute of Neuroscience I saw animals in calm, healthy conditions, to which the tests were just a part of their daily routine. Animal testing is controversial but I think that the work of Professor Baker and his team is important in helping people who have suffered stroke and other life-changing trauma to regain their independence and, often, their lives.

Source: Newcastle University

Source: New wearable electronic device could revolutionise treatment for stroke patients

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