Scientists Capture How Glutamate Opens Neuron Signaling Channels

 Your incompetent doctor and hospital have done nothing to stop the glutamate poisoning part of the neuronal cascade of death I bet! And this research won't trigger ways to stop that problem, will it?

glutamate poisoning (6 posts to July 2020)

And I'm sure they DID NOTHING with this either!

generic drug candesartan (brand name: ATACAND®) Blood Pressure Drug Helps Alzheimer's June 2018

 This line from there is instructive:

The scientists found that candesartan prevented glutamate-induced neuronal death. 

The latest here:

Scientists Capture How Glutamate Opens Neuron Signaling Channels

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Reviewed

Johns Hopkins MedicineMar 29 2025

In an effort to understand how brain cells exchange chemical messages, scientists say they have successfully used a highly specialized microscope to capture more precise details of how one of the most common signaling molecules, glutamate, opens a channel and allows a flood of charged particles to enter. The finding, which resulted from a study led by Johns Hopkins Medicine researchers, could advance the development of new drugs that block or open such signaling channels to treat conditions as varied as epilepsy and some intellectual disorders. 

A report on the experiments, funded by the National Institutes of Health and in collaboration with scientists at UTHealth Houston, was published March 26 in the journal Nature. 

Neurons are the cellular foundation of the brain, and the ability to experience our environment and learn depends on [chemical] communications between neurons."

Edward Twomey, Ph.D., assistant professor of biophysics and biophysical chemistry at the Johns Hopkins University School of Medicine

Scientists have long known that a major molecule responsible for neuron-to-neuron communications is the neurotransmitter glutamate, a molecule abundant in the spaces between neurons. Its landing place on neurons is a channel called an AMPA receptor, which interacts with glutamate, and then acts like a pore that takes in charged particles. The ebb and flow of charged particles creates electrical signals that form communications between neurons. 

To figure out details of the miniscule movements of AMPA receptors (at the level of single atoms), researchers used a very high-powered microscope to image these channels during specific steps in the communications processes. For the study, the scientists used a cryo-electron microscope (cryo-EM) in a facility at the Johns Hopkins University School of Medicine. 

Typically, scientists find it easier to study cell samples that are chilled, a state that provides a stable environment. But at normal body temperature, Twomey's team found that the AMPA receptors and glutamate activity increased, providing more opportunities to capture this process in cryoEM images. 

To that end, the scientists purified AMPA receptors, taken from lab-grown human embryonic cells that are used widely in neuroscience research to produce such proteins. Then, they heated the receptors to body temperature (37 degrees Celsius or 98.6 degrees Fahrenheit) before exposing them to glutamate. Immediately after this, the receptors were flash frozen and analyzed with cryoEM to get a snapshot of the AMPA receptors bound to the major signaling molecule, glutamate. 

After assembling more than a million images taken with cryoEM, the team found that glutamate molecules act like a key that unlocks the door to the channel, enabling it to open more widely. This occurs by the clamshell-like structure of the AMPA receptor closing around glutamate, an action that pulls open the channel below. 

Twomey's previous research has shown that drugs such as perampanel, used to treat epilepsy, act as a door stopper around the AMPA receptor to limit the channel from opening and reducing the abundance of activity known to happen in brain cells of people with epilepsy. 

Twomey says the findings could be used to develop new drugs that bind to AMPA receptors in different ways that either open or close the signaling channels of brain cells. 

"With each new finding, we are figuring out each of the building blocks that enable our brains to function," says Twomey. 

Additional scientists who contributed to the work are Anish Kumar Mondal from Johns Hopkins and Elisa Carrillo and Vasanthi Jayaraman from UTHealth Houston.

Funding for the research was provided by the National Institutes of Health (R35GM154904, R35GM122528), the Searle Scholars Program and the Diana Helis Henry Medical Research Foundation.

Source:

Johns Hopkins Medicine

Journal reference:

Mondal, A. K., et al. (2025). Glutamate gating of AMPA-subtype iGluRs at physiological temperatures. Nature. doi.org/10.1038/s41586-025-08770-0.

Lab-Grown Neurons Mimic Brain Networks, Exhibit Neuroplasticity

 The simple next goal is to listen in on neurons signaling each other to drop your current function and take on your neighbors' functions. You can easily do that by these methods.  Until that is figured out neuroplasticity will never be repeatable on demand.  

1. Use nanowires to listen in on single neurons

2. Or lay a grid across the cortex to listen in. 

Lab-Grown Neurons Mimic Brain Networks, Exhibit Neuroplasticity

Summary: Researchers have developed lab-grown neurons that behave more like real brain networks, advancing the study of learning and memory. Using microfluidic devices, the neurons formed diverse and functional networks, resembling those seen in living nervous systems.

These networks exhibited complex activity patterns and showed neural plasticity, reconfiguring in response to repetitive stimulation. This breakthrough provides scientists with a powerful new tool to study brain functions under controlled lab conditions.

Key Facts

• Realistic Networks: Microfluidic devices enabled neurons to form natural-like brain networks.
• Neural Plasticity: Repeated stimulation altered neuronal ensembles, mimicking learning processes.
• Advanced Models: This technology can be used to study memory formation and brain function.

Source: Tohoku University

“Neurons that fire together, wire together” describes the neural plasticity seen in human brains, but neurons grown in a dish don’t seem to follow these rules. Neurons that are cultured in-vitro form random and meaningless networks that all fire together. They don’t accurately represent how a real brain would learn, so we can only draw limited conclusions from studying it.

But what if we could develop in-vitro neurons that actually behaved more naturally?

A research team at Tohoku University has used microfluidic devices to reconstitute biological neuronal networks bearing connectivity resembling that found in animal nervous systems.

By changing the size and shape of the tiny tunnels (called microchannels) that connect the neurons, the team controlled how strongly the neurons interacted. Credit: Neuroscience News

They showed that such networks exhibit complex activity patterns that were able to be “reconfigured” by repetitive stimulation. This remarkable finding provides new tools for studying learning and memory.

The results were published online in Advanced Materials Technologies on November 23, 2024.

In certain areas of the brain, information is encoded and stored as “neuronal ensembles,” or groups of neurons that fire together. Ensembles change based on input signals from the environment, which is considered to be the neural basis of how we learn and remember things. However, studying these processes using animal models is difficult because of its complex structure.

“The reason there is a need to grow neurons in the lab is because the systems are much simpler,” remarks Hideaki Yamamoto (Tohoku University), “Lab-grown neurons allow scientists to explore how learning and memory work in highly controlled conditions. There is a demand for these neurons to be as close to the real thing as possible.”

The research team created a special model using a microfluidic device–a small chip with tiny 3D structures. This device allowed neurons to connect and form networks similar to those in the animals’ nervous system. By changing the size and shape of the tiny tunnels (called microchannels) that connect the neurons, the team controlled how strongly the neurons interacted.

The researchers demonstrated that networks with smaller microchannels can maintain diverse neuronal ensembles. For example, the in-vitro neurons grown in traditional devices tended to only exhibit a single ensemble, while those grown with the smaller microchannels showed up to six ensembles.

Additionally, the team found that repeated stimulation modulates these ensembles, showing a process resembling neural plasticity, as if the cells were being reconfigured.

This microfluid technology in conjunction with in-vitro neurons could be used in the future to develop more advanced models that can mimic specific brain functions, like forming and recalling memories.

About this neuroplasticity research news

Author: Public Relations
Source: Tohoku University
Contact: Public Relations – Tohoku University
Image: The image is credited to Neuroscience News

Original Research: Open access.
“Precision Microfluidic Control of Neuronal Ensembles in Cultured Cortical Networks” by Hideaki Yamamoto et al. Advanced Materials Technologies

A review of the progression and future implications of brain-computer interface therapies for restoration of distal upper extremity motor function after stroke

If you were to properly think about this, all rehab therapies would work much better with vastly fewer dead neurons. And you do that by stopping the 5 causes of the neuronal cascade of death in the first week.

If my doctors had done that they would have saved me  5.4 billion neurons. Recovery would have been easy with only 171 million dead neurons.  And sending a bill to my doctor and stroke hospital at $1000 a dead neuron would only cost them 5.4 trillion dollars. That might concentrate their minds.  I don't expect neuroplasticity or neurogenesis to be precisely repeatable for at least 50 years. No one is looking at the signals that occur between neurons such that one neuron drops its current function and takes on a neighbor's function. Knowing that process is the only way to make neuroplasticity EXACTLY REPEATABLE.

A review of the progression and future implications of brain-computer interface therapies for restoration of distal upper extremity motor function after stroke

 Alexander Remsik, Brittany Young, Rebecca Vermilyea, Laura Kiekhoefer, Jessica Abrams, Samantha Evander Elmore,Paige Schultz, Veena Nair, Dorothy Edwards, Justin Williams and Vivek Prabhakaran
Department of Radiology Clinical Science Center, University of Wisconsin Madison School of Medicine and Public Health Ringgold StandardInstitution, Madison, WI, USA

 ABSTRACT

Stroke is a leading cause of acquired disability resulting in distal upper extremity functional motor impairment. Stroke mortality rates continue to decline with advances in healthcare and medical technology. This has led to an increased demand for advanced, personalized rehabilitation. Survivors often experience some level of spontaneous recovery shortly after their stroke event, yet reach a functional plateau after which there is exiguous motor recovery. Nevertheless, studies have demonstrated the potential for recovery beyond this plateau. Non-traditional neurorehabilitation techniques,such as those incorporating the brain-computer interface (BCI), are being investigated for rehabilitation. BCIs may offer a gateway to the brain’s plasticity and revolutionize how humans interact with the world.Non-invasive BCIs work by closing the proprioceptive feedback loop with real-time, multi-sensory feedback allowing for volitional modulation of brain signals to assist hand function. BCI technology potentially promotes neuroplasticity and Hebbian-based motor recovery by rewarding cortical activity associated with sensory-motor rhythms through use with a variety of self-guided and assistive modalities. (So you really know nothing useful?)
 

These tiny, ultra-low power chips are helping scientists to understand your mind

Now all we need is for our stroke medical leadership to do the following:
1.  Describe the problem exactly How and why does a neuron drop its' current task and take up a neighbors? Neuroplasticity in action?
2.  Write an RFP to researchers to solve that problem.
3.  Fund them with foundation grants.
4.  Write stroke rehab protocols based on the research.
5.  Get the Nobel prize in medicine  

These tiny, ultra-low power chips are helping scientists to understand your mind

Researchers at Purdue University are developing chips that could help scientists understand nerve conditions, and potentially help lay the foundations for neuroprosthetics.

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You don't need to be a research scientist to know that the human brain is a sensitive organ: each square millimetre of the brain contains tens of thousands of neurons -- the electrical wiring that communicates messages around the brain.
While measuring the electrical activity of those neurones with external probes or implants can give researchers and medical professionals an insight into the brain's functioning, introducing external hardware to the brain is not without risk.
Brain implants need to be as small as possible to reduce the chance that they could disrupt the brain's functioning. But, thanks to the density of those tightly packed neurons, any chip used to monitor a human brain must be capable of obtaining and processing huge amounts of information.
Tiny, low-power, high-throughput chips that can sit comfortably on the human brain: not exactly the easiest hardware to build, but chips that can do all these things is vital to further research into brain and central nervous system disorders.
By making a chip that can gather information about the workings of the brain, without disturbing or harming the sensitive structures within, researchers at Purdue University, in Indiana are hoping to create a tool that can provide better support to people with neurological disorders.

The researchers have created a tiny chip that picks up signals from the brain or the nervous system, and sends them wirelessly outside the body for analysis, without the need for a battery, according to the university.

Creating the chip was the work of three years, Saeed Mohammadi, an associate professor in Purdue's School of Electrical and Computer Engineering department, told ZDNet.
"The idea was 'can we make this as small as possible?' So we looked at what are the possible ways to make the system small -- it shouldn't have a battery, it shouldn't have any external components, it should just be a small chip, and everything should be on a small chip. So, we worked hard to integrate the antenna on it, we worked hard to replace the battery with wireless power," he said.
In order to keep the chip as small as possible (it's now in the region of 1mm by 0.5mm), the researchers took to redesigning its antenna in a spiral pattern -- a decision that allowed them to keep the antenna as long as possible while still shrinking the volume of space needed to contain it.
"Usually antennas are large, especially as this is a low-frequency [one] at 1Ghz, and when you calculate the size of the antenna, it should be several centimetres... Part of it we spiralled around itself to make it small, while the main part, which is responsible for detecting the majority of the signal, is straight. By doing this trick, we were able to make the antenna small and still very efficient," Mohammadi said.
Currently, Purdue's prototype chip has four channels -- a small fraction of what would be needed for a commercial neural probe, but enough to prove the system could be used.
"We have to add a lot more neural sites to be able to take out many, many more neural signals. Right now, the chip only has four or them, but we need a lot more -- people use probes that have 64 or 128 channels to look at different sites. We're working on expanding the numbers, so we're hoping to be able to add more of these neural sites, and that makes the device a little bit larger," Mohammadi said. Expanding the chip to 64 channels should take another year, he added.
The researchers will also be working on other improvements, such as boosting the speed of the interface circuit that digitises the signal from the neural site without significantly increasing the chip's overall power requirement at the same time. Similarly, as the number of neural sites the chip can read grows, the Purdue researchers are planning to increase the speed of wireless communication between the chip and the external computer that receives the data.

Those aren't the only balancing acts the team will need to pull off before their brain-reading implants can be used on humans. One of the difficulties of making electronics that can interface with brains is accommodating the movement of the organ. Like most non-bony structures in the body, the brain isn't static: it pulsates, so any electronics that touch must have a degree of flexibility to move alongside.
"If this doesn't move with the brain's movement, it could injure the neurons. Over time, people who have used these probes have noticed the signal is lost... if your electrode is flexible and can move with the brain tissue, you'll have less injury and a better chance of getting a signal over a long time," Mohammedi said.
While the Purdue researchers have typically used their chip for only minutes at a time, they've designed it to be flexible enough, and low powered enough, that it could potentially stay in the body for a longer period, and ultimately see later generations of the chip used in the long-term monitoring of brain health.
The dinky chip has its origins in hardware intended to monitor soil conditions, such as temperature and humidity, according to Mohammedi. "The idea was to have a piece of dust that could, if you put it inside the soil, detect the nitrate or nitrite level, or the nutrition of the soil, and monitor the growth condition of the plant. This would be useful for agriculture. We had some work in that area, and it was not too hard to attach the neural sensor to this device to do essentially the same thing."
In the shorter term, the chip is likely to be used in monitoring neurodegenerative diseases such as Parkinson's or ALS in animal models to help better understand and research the conditions.
In the more distant future, however, the chip could help repair nerve injuries by acting as a bridge between two parts of a nerve that have become severed. "If someone has a nerve injury you could put two of these devices on each and reconnect them with wireless communication," Mohammadi said. It could also be used to connect the brain and other parts of the nervous system, underpinning neuroprosthetics. "That would be 20 years down the road, there's a long way to go."

Tiny fibers open new windows into the brain

The solution to finding out exactly how neuroplasticity works is right here.  What signals is a neuron sending to a neighbor to get it to drop its current functionality and take on new functionality? If we had ANY stroke leadership and strategy we could submit an RFP to researchers to figure this out and make a protocol out if it. Thus short cutting the process of neuroplasticity by months or years and millions of repetitions.
Which research team is your stroke hospital working with? Not working with any is pure incompetency.
But this will never occur since we have fucking failures of stroke associations.
https://www.sciencedaily.com/releases/2017/02/170222145750.htm

Three-in-one design allows genetic, chemical, optical, and electrical inputs and outputs.

Date:

February 22, 2017

Source:

Massachusetts Institute of Technology

Summary:

For the first time, a single multifunction flexible fiber no bigger than a human hair, has successfully delivered a combination of optical, electrical and chemical signals back and forth into the brain.

For the first time ever, a single flexible fiber no bigger than a human hair has successfully delivered a combination of optical, electrical, and chemical signals back and forth into the brain, putting into practice an idea first proposed two years ago. With some tweaking to further improve its biocompatibility, the new approach could provide a dramatically improved way to learn about the functions and interconnections of different brain regions.

The new fibers were developed through a collaboration among material scientists, chemists, biologists, and other specialists. The results are reported in the journal Nature Neuroscience, in a paper by Seongjun Park, an MIT graduate student; Polina Anikeeva, the Class of 1942 Career Development Professor in the Department of Materials Science and Engineering; Yoel Fink, a professor in the departments of Materials Science and Engineering, and Electrical Engineering and Computer Science; Gloria Choi, the Samuel A. Goldblith Career Development Professor in the Department of Brain and Cognitive Sciences, and 10 others at MIT and elsewhere.
The fibers are designed to mimic the softness and flexibility of brain tissue. This could make it possible to leave implants in place and have them retain their functions over much longer periods than is currently possible with typical stiff, metallic fibers, thus enabling much more extensive data collection. For example, in tests with lab mice, the researchers were able to inject viral vectors that carried genes called opsins, which sensitize neurons to light, through one of two fluid channels in the fiber. They waited for the opsins to take effect, then sent a pulse of light through the optical waveguide in the center, and recorded the resulting neuronal activity, using six electrodes to pinpoint specific reactions. All fof this was done through a single flexible fiber just 200 micrometers across -- comparable to the width of a human hair.
Previous research efforts in neuroscience have generally relied on separate devices: needles to inject viral vectors for optogenetics, optical fibers for light delivery, and arrays of electrodes for recording, adding a great deal of complication and the need for tricky alignments among the different devices. Getting that alignment right in practice was "somewhat probabilistic," Anikeeva says. "We said, wouldn't it be nice if we had a device that could just do it all."
After years of effort, that's what the team has now successfully demonstrated. "It can deliver the virus [containing the opsins] straight to the cell, and then stimulate the response and record the activity -- and [the fiber] is sufficiently small and biocompatible so it can be kept in for a long time," Anikeeva says.
Since each fiber is so small, "potentially, we could use many of them to observe different regions of activity," she says. In their initial tests, the researchers placed probes in two different brain regions at once, varying which regions they used from one experiment to the next, and measuring how long it took for responses to travel between them.
The key ingredient that made this multifunctional fiber possible was the development of conductive "wires" that maintained the needed flexibility while also carrying electrical signals well. After much work, the team was able to engineer a composite of conductive polyethylene doped with graphite flakes. The polyethylene was initially formed into layers, sprinkled with graphite flakes, then compressed; then another pair of layers was added and compressed, and then another, and so on. A member of the team, Benjamin Grena, a recent graduate in materials science and engineering, referred to it as making "mille feuille," (literally, "a thousand leaves," the French name for a Napoleon pastry). That method increased the conductivity of the polymer by a factor of four or five, Park says. "That allowed us to reduce the size of the electrodes by the same amount."
One immediate question that could be addressed through such fibers is that of exactly how long it takes for the neurons to become light-sensitized after injection of the genetic material. Such determinations could only be made by crude approximations before, but now could be pinpointed more clearly, the team says. The specific sensitizing agent used in their initial tests turned out to produce effects after about 11 days.
The team aims to reduce the width of the fibers further, to make their properties even closer to those of the neural tissue. "The next engineering challenge is to use material that is even softer, to really match" the adjacent tissue, Park says. Already, though, dozens of research teams around the world have been requesting samples of the new fibers to test in their own research.

---

Story Source:
Materials provided by Massachusetts Institute of Technology. Original written by David L. Chandler. Note: Content may be edited for style and length.

---

Journal Reference:

1. Seongjun Park, Yuanyuan Guo, Xiaoting Jia, Han Kyoung Choe, Benjamin Grena, Jeewoo Kang, Jiyeon Park, Chi Lu, Andres Canales, Ritchie Chen, Yeong Shin Yim, Gloria B Choi, Yoel Fink, Polina Anikeeva. One-step optogenetics with multifunctional flexible polymer fibers. Nature Neuroscience, 2017; DOI: 10.1038/nn.4510

Blocking neuron signaling pathway could lead to new treatments for peripheral neuropathy

You have to read between the lines to find possible uses for stroke. Blocking neuron signaling could be repurposed to block aberrant signals that cause spasticity. But no one will ever think of that or act on it.
https://www.mdlinx.com/internal-medicine/medical-news-article/2017/01/25/peripheral-neuropathy-molecular-signaling-pathway/7023028/?

UC San Diego Health System News, 01/25/2017

Researchers at University of California San Diego School of Medicine, with colleagues at the National Institute of Diabetes and Digestive and Kidney Diseases, the University of Manitoba and St. Boniface Hospital Albrechtsen Research Centre in Canada, have identified a molecular signaling pathway that, when blocked, promotes sensory neuron growth and prevents or reverses peripheral neuropathy in cell and rodent models of type 1 and 2 diabetes, chemotherapy–induced neuropathy and HIV.

The findings were published in the January 17, 2017 issue of the Journal of Clinical Investigation.

“Peripheral neuropathy is a major and largely untreated cause of human suffering,” said first author Nigel Calcutt, PhD, professor of pathology at UC San Diego School of Medicine. “It has huge associated health care costs.”

Previous research has described at least some of the fundamental processes involved in healthy, on–going peripheral nerve growth regeneration, including the critical role of mitochondria — cellular organelles that produce adenosine triphosphate (ATP), the energy–carrying molecule found in all cells that is vital to driving nerve recovery after injury.

In their JCI paper, the researchers looked for key molecules and mechanisms used in sensory neuron growth and regrowth. In particular, they noted that the outgrowth of neurites — projections from a neuronal cell body that connect it to other neurons — was constrained by activation of muscarinic acetylcholine receptors. This was surprising, they said, because acetylocholine is a neurotransmitter usually associated with activation of cells.

With identification of this signaling pathway, the scientists suggest it is now possible to investigate the utility of anti–muscarinic drugs already approved for use in other conditions as a new treatment for peripheral neuropathy.

“This is encouraging because the safety profile of anti–muscarinic drugs is well–characterized, with more than 20 years of clinical application for a variety of indications in Europe,” said senior study author Paul Fernyhough, PhD, professor in the departments of pharmacology and therapeutics and physiology at the University of Manitoba in Canada. “The novel therapeutic application of anti–muscarinic antagonists suggested by our studies could potentially translate relatively rapidly to clinical use.”

Go to Abstract Print Article Summary Cat 2 CME Report

How Neurons Talk to Each Other

Is your doctor telling you all about how the brain works and how you will recover? Probably not, because your doctor knows nothing about your recovery. Ask her/him. I bet you don't get a coherent answer.
http://neurosciencenews.com/neurons-synapses-neuroscience-5119/
Summary: A new paper offers an overview as to how neurons ‘communicate’ with one another.
Source: Max Planck Institute.
Neurons are connected to each other through synapses, sites where signals are transmitted in the form of chemical messengers. Reinhard Jahn, Director at the Max Planck Institute for Biophysical Chemistry in Göttingen, has investigated precisely how the process works.
Our nervous system consists of about 100 billion interlinked neurons that are capable of carrying out complex computations. Each neuron has an antenna zone comprising the cell body and its extensions (dendrites). It is here that it receives signals from other neurons.
One cell talks, the other listens
The signals are then computed and forwarded by a “cable”, the axon, in the form of electrical impulses. In the emitter region, the axon branches to form contact sites, known as synapses, where the signals are transmitted to other neurons. At the synapse, electrical impulses arriving from the axon are converted into chemical signals. The information then flows in only one direction: one cell talks, the other listens. The number of synapses that a single neuron can develop varies considerably. Depending on its type, a neuron can have anything from just one to more than 100,000 synapses. On average, each neuron has around 1,000 synapses.
Synapses – elementary units of neuronal information transmission
Synapses consist of:

• the nerve ending of the transmitting (presynaptic) neuron,
• the synaptic cleft separating the transmitting and receiving neurons and
• the membrane of the receiving (postsynaptic) neuron.

The presynaptic nerve endings contain signal molecules known as neurotransmitters, which are stored in small membrane-enclosed vesicles. Each nerve ending in the central nervous system contains an average of several hundred synaptic vesicles. However, synapses vary significantly. For example, some specialist synapses contain more than 100,000 vesicles. They include the synapses that control our muscles. At each synapse some vesicles are always in the starting position, “lurking”, as it were, on the presynaptic plasma membrane to which they have docked.
Molecular machines at work
An electrical signal arriving at the nerve ending activates calcium channels in the plasma membrane. Calcium ions from outside then flow through the channels into the interior of the synapse. There, the inflowing calcium ions encounter and activate a molecular machine located between the vesicle membrane and the plasma membrane. This machine causes the membranes of the vesicles in the starting position to fuse with the plasma membrane and release the neurotransmitters contained in the vesicles into the synaptic cleft.

Illustration of a neuron (left) and a synapse (right). NeuroscienceNews.com image is credited to MPI for Biophysical Chemistry.

On the other side of the synaptic cleft, the neurotransmitters come into contact with docking sites on the membrane of the receiving neuron which regulate the electrical properties of that membrane. This alters the electrical resistance of the membrane. The receiving cell is able to process the resulting potential change rapidly. Only around one thousandth of a second elapses between the arrival of an impulse and the potential change on the other side of the synaptic cleft. In fact, synaptic transmission is one of the fastest biological processes known. Nevertheless, it is positively sluggish in comparison to a transistor.
Synaptic vesicles: not just storage organelles
A synaptic vesicle is not just a kind of membrane-bound “storage tank” for neurotransmitters. Its membrane contains a whole series of proteins that have barely changed over millions of years of evolution. A group of these proteins, the neurotransmitter transporters, are responsible for pumping neurotransmitters from the cytoplasm into the vesicles, where they accumulate. This process requires a great deal of energy, which is provided by another protein molecule, proton ATPase (V-ATPase), that pumps protons into the vesicles – a process that is fuelled by adenosine triphosphate (ATP). The pumps, in turn, use the resulting concentration gradient for the uptake of neurotransmitters.
In addition to these proteins required for “replenishing”, the membranes of synaptic vesicles contain other components that enable the vesicles to fuse with the plasma membrane (including the SNARE protein synaptobrevin and the calcium sensor synaptotagmin). Once membrane fusion has occurred, they are transported back into the nerve ending. The synaptic vesicles are then recycled back into the nerve ending via several intermediate steps and are refilled with neurotransmitters. This process is repeated again and again, thousands of times in the life cycle of a vesicle.
The process by which synaptic vesicles function at the molecular level is intricate. Several years ago, we created a comprehensive inventory of all vesicle components. Because vesicles are tiny and complex in composition, this undertaking was not easy. Several teams from Germany, Japan, Switzerland and the United States collaborated for years in order to identify the protein and fat components of vesicles and develop a quantitative molecular model of a standard vesicle.
First, problems had to be solved that were not as straightforward as one might suppose, for example counting the number of vesicles in a solution and determining the quantities of proteins and membrane lipids present. The results were surprising even for experts. It turned out that the structure of a biological transport vesicle is shaped to a far greater extent by proteins than was previously thought: If the vesicle model is looked at from the outside, the lipid membrane (yellow) can barely be seen for the sheer number of proteins. Yet the model only contains around 70 percent of the total quantity of protein present.

Molecular model of a synaptic vesicle showing the main proteins. NeuroscienceNews.com image is credited to MPI for Biophysical Chemistry.

This work formed the basis for further investigations. It has meanwhile been possible to distinguish the vesicles that transport various neurotransmitters from each other and to compare them. Contrary to what was believed, they differ only slightly in their composition. In addition, various vesicles that had already docked to the plasma membrane were isolated, allowing their protein composition to be analyzed as well.
How do the membranes fuse?
A second aim of the research is to gain an understanding of the functional details of the protein machine responsible for membrane fusion. The proteins involved have been characterized for over a decade, but is still not clear how they manage to fuse the membranes within less than one millisecond following an influx of calcium ions.
SNARE proteins – small protein molecules that reside in the plasma membrane and vesicle membrane − are responsible for the fusion process itself. Whenever the membranes approach each other, the proteins stack on top of each other, twisting together like ropes in the direction of the membrane.
This stacking process releases energy, which is used for fusing the membranes. Recent studies have shown that the twisted bundles extend into the membrane.
To understand how this stacking causes the membranes to fuse, the SNARE proteins were incorporated into artificial membranes, which could be observed using high-resolution methods such as cryo-electron microscopy. For the first time, intermediate stages of the fusion reaction were identified. This made it possible to develop a model of the individual steps at the molecular level.
Progress has also been achieved regarding the question of how the inflowing calcium ions activate the fusion machine. This is mediated by another protein in the membrane of synaptic vesicles, synaptotagmin, which binds the calcium ions and then draws the membranes closer together.
Despite considerable progress, the complex molecular processes are still not fully understood. It is all the more astonishing how smoothly neurons communicate with each other and how effectively the fusion machinery works in the synapse to effect our every movement, emotion and thought. Scientists the world over therefore continue to focus on the fusion machine in order to gain a better understanding of these processes. There is justified hope that such knowledge will also improve our understanding of neurodegenerative diseases such as Parkinson’s, Alzheimer’s and Huntington’s disease.

About this neuroscience research article

Source: Reinhard Jahn – Max Planck Institute
Image Source: NeuroscienceNews.com images are credited to MPI for Biophysical Chemistry.

Lund researchers one step closer to developing implantable electrodes for capturing brain function

Which one of these is your doctor studying and using to see how best to identify how your brain is communicating? Is your doctor thinking at all or just spouting crap from medical school?

Ultra-flexible, thin-film electrode arrays for chronic neural recording and stimulation of brain cavity wall

Three-dimensional macroporous nanoelectronic networks as minimally invasive brain probes

New technology facilitates studies of brain cells in stroke

Nanowire Tetrodes

First signals from brain nerve cells with ultrathin nanowires

 

 

Lund researchers one step closer to developing implantable electrodes for capturing brain function 

For nearly nine years, researchers at Lund University have been working on developing implantable electrodes that can capture signals from single neurons in the brain over a long period of time - without causing brain tissue damage. They are now one big step closer to reaching this goal, and the results are published in the scientific journal Frontiers in Neuroscience.
This technology would make it possible to understand brain function in both healthy and diseased individuals.
"There are several elements that must go hand in hand for us to be able to record neuronal signals from the brain with decisive results. First, the electrode must be bio-friendly, that is, we have to be confident that it does not cause any significant damage to the brain tissue. Second, the electrode must be flexible in relation to the brain tissue. Remember that the brain floats in fluid inside the skull and moves around when we, for instance, breathe or turn our heads.
The electrode and the implantation technology that we have now developed have these properties, which is unique", says Professor Jens Schouenborg who together with Dr Lina Pettersson led the project.
The Lund researchers' tailored electrodes, which they call 3-D electrodes, are unique in that they are extremely soft and flexible in all three dimensions, in a way that enables stable recordings from the neurons over a long time.
The electrode is so soft that it deflects against a water surface. In order to implant such electrodes, the researchers have developed a technique for encapsulating the electrodes in a hard but dissolvable gelatine material that is also very gentle on the brain.

"This technology retains the electrodes in their original form inside the brain and can monitor what happens inside virtually undisturbed and normally functioning brain tissue", says Johan Agorelius, a doctoral student in the project.
Until now, developed flexible electrodes have not been able to maintain their shape when implanted, which is why they have been fixated on a solid chip that limits their flexibility, among other things. Other types of electrodes that are used are much stiffer. The result in both cases is that they rub against and irritate the brain tissue, and the nerve cells around the electrodes die.
"The signals then become misleading or completely non-existent. Our new technology enables us to implant as flexible electrodes as we want, and retain the exact shape of the electrode within the brain", says Johan Agorelius.
"This creates entirely new conditions for our understanding of what happens inside the brain and for the development of more effective treatments for diseases such as Parkinson's disease and chronic pain conditions than can be achieved using today's techniques", concludes Jens Schouenborg.
Facts about the electrodes:
The electrodes are made of 4 mmgold leads and individually insulated with 4 mm parylene. The array of electrodes consists of eight flexible channels, designed to follow the movement of the brain.
Both the electrode and implantation technology, which have been tested on rats, are patented by NRC researchers, in Europe and the US, among other places.

Source:

Lund University

Three-dimensional macroporous nanoelectronic networks as minimally invasive brain probes

This seems  like it would be very useful for our stroke researchers to listen in on neurons talking to each other. Then we could maybe find out exactly how neuroplasticity works. Why would a neuron give up its' current task to help out a neighboring neuron? How is that accomplished? Without knowing these answers neuroplasticity is not consistently repeatable. Which means that none of the research into neuroplasticity is valid right now.
The other possibilities for listening in on the brain:

Ultra-flexible, thin-film electrode arrays for chronic neural recording and stimulation of brain cavity wall

New technology facilitates studies of brain cells in stroke

Nanowire Tetrodes

First signals from brain nerve cells with ultrathin nanowires

 

 

 The latest here:

Three-dimensional macroporous nanoelectronic networks as minimally invasive brain probes

• Chong Xie,
• Jia Liu,
• Tian-Ming Fu,
• Xiaochuan Dai,
• Wei Zhou
• & Charles M. Lieber

• Affiliations
• Contributions
• Corresponding author

Nature Materials

(2015)

doi:10.1038/nmat4427

Received

12 May 2015

Accepted

19 August 2015

Published online

05 October 2015

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Abstract

• Abstract•
• References•
• Author information•
• Supplementary information

Direct electrical recording and stimulation of neural activity using micro-fabricated silicon and metal micro-wire probes have contributed extensively to basic neuroscience and therapeutic applications; however, the dimensional and mechanical mismatch of these probes with the brain tissue limits their stability in chronic implants and decreases the neuron–device contact. Here, we demonstrate the realization of a three-dimensional macroporous nanoelectronic brain probe that combines ultra-flexibility and subcellular feature sizes to overcome these limitations. Built-in strains controlling the local geometry of the macroporous devices are designed to optimize the neuron/probe interface and to promote integration with the brain tissue while introducing minimal mechanical perturbation. The ultra-flexible probes were implanted frozen into rodent brains and used to record multiplexed local field potentials and single-unit action potentials from the somatosensory cortex. Significantly, histology analysis revealed filling-in of neural tissue through the macroporous network and attractive neuron–probe interactions, consistent with long-term biocompatibility of the device.

Development of flexible μECoG electrode arrays for chronic use in brain cavities

And maybe with this our researchers could listen in on neuron signalling and figure out precisely how neuroplasticity works. Why would a neuron give up its current job and switch careers to a neighboring neuron?
https://lirias.kuleuven.be/handle/123456789/457677

Authors:	Ceyssens, Frederik van Kuyck, Kris Deprez, Marjolijn Nica, Ioana Gabriela Aerts, Jean-Marie Nuttin, Bart Puers, Bob
Issue Date:	Jun-2014
Conference:	Neural Interfacing Conference location:Dallas date:June 2014
Abstract:	Ultra-flexible thin film microelectrode arrays were designed, fabricated and tested in vitro and in vivo, aiming at μEcoG and neurostimulation applications in the wall of brain cavities arising after e.g. hemorrhage or tumor resection. In order to conform to cavity walls and to minimize irritation, the arrays were designed in a tree or web shape for high bendability over a 5 mm radius sphere. Compared to an unpatterned sheet, the required bending energy per area was reduced by 95%. The very low total thickness of 7 μm further adds to the bendability. The arrays carry 100 μm and 350 μm diameter electrodes, for a charge injection capacity of 75 μC/phase/cm2 for Pt and 2000 μC/phase/cm2 for sputtered IrOx. Fabrication was done using lithographic techniques. The arrays consist of a polyimide-Pt-polyimide structure. An improved fabrication process was designed in order to enhance insulation lifetime in a saline environment. In accelerated aging tests at 87 degrees C, this process has been shown to improve lifetime by a factor 7.4 comparing to the state of the art. Similar lifetime tests were done to select the connector's underfill isolation. Finally, in vivo tests in freely moving rats have shown satisfying operation of the implants in neural recording and stimulation over a period of at least 3 months.

Visualizing Cell Signaling: Current Trends and New Technologies

This sounds like something our doctors and researchers need to attend so they  can figure out how neurons neuroplastically get their neighboring neurons to help. And with that knowledge we could finally have repeatable stroke protocols for recovery of functions. Instead of todays' world where no one knows how it works and all we get is repetition, repetition, repetition.
http://webinar.sciencemag.org/webinar/archive/visualizing-cell-signaling

Wednesday, April 16, 2014

12:00 pm ET

06:23:55 Days Hrs Mins

Register Now

Techniques for the study of intracellular ions are used widely in biology, including for the tracking of calcium waves or ions affecting pH within living cells. The ability to monitor changes in intracellular ion concentrations over time is vital for our understanding of signaling and functional pathways in cellular systems. These pathways are central to many fundamental processes such as muscle contraction and synaptic nerve signal transmission. Ion channels that span the outer cell membrane open or close in response to extracellular and intracellular signals, potentially altering how the cell behaves. These fluctuations can be visualized and quantified using ratiometric microscopy and special fluorescent dyes designed to bind specific ions, such as the FURA-2 indicator dye specific to calcium ions. Changes in the photophysics of the dye as it binds to its target ion allows for quantitation of the bound and unbound ratio, and thus the concentration of the ion under investigation. This webinar will introduce the viewer to the current state of technology in this important field as well as cover the latest advances in microscopy for ion signaling research.
During the webinar, viewers will:

• Learn about current state-of-the-art ion signaling methodologies
• Discover what recent advances have been made in technologies for tracking ion changes, particularly calcium signaling
• Hear how experts in the field are applying these new technologies in the lab today
• Have the opportunity to ask questions of the expert panel live!

Speaker Bios

Mark Hollywood, Ph.D.

Dundalk Institute of Technology
Dundalk, Ireland

Dr. Hollywood undertook his Ph.D. at Queens University in Belfast, Ireland on the innervation of sheep mesenteric lymphatics. Following graduation in 1994, he commenced postdoctoral training in the Smooth Muscle Group and subsequently was offered a lecturer position in the Department of Physiology in 1995 and a senior lecturer post in 2001. In 2005, Dr. Hollywood together with his colleagues from the Smooth Muscle Group were recruited by Dundalk Institute of Technology to set up the Smooth Muscle Research Centre in Ireland, where he is currently a principal investigator. Dr. Hollywood’s research interests are focused on (1) developing novel ion channel modulators to treat overactive bladder and (2) examining the mechanisms underlying spontaneous activity in urethral pacemaker cells and how they modulate the bulk smooth muscle. His laboratory is currently developing a combined patch clamp/confocal microscopy system that will allow simultaneous imaging of whole-cell Ca2+ at frame rates in excess of 200 frames per second using back-illuminated EMCCD cameras, and enable correlation of this data to the resultant electrical activity observed in isolated urethral pacemaker cells.

C. Peter Bengtson, Ph.D.

University of Heidelberg
Heidelberg, Germany

Dr. Bengtson has a Ph.D. in neurophysiology from the Department of Physiology and Pharmacology at the University of Queensland, Australia.  He specializes in both patch clamp electrophysiology and wide-field microscopy from neurons in brain slices or dissociated cultures. He is currently a senior postdoctoral fellow in the Department of Neurobiology in the Interdisciplinary Center for Neuroscience (IZN) at Heidelberg University where he has worked for over a decade in the laboratory of Professor Hilmar Bading, primarily investigating the calcium signals and molecular mechanisms mediating long-term plasticity and memory.

Colin Coates, Ph.D.

Andor Technology
Belfast, Ireland

Dr. Coates holds a first-class degree in chemistry, with a postgraduate degree and postdoctoral research training from Queen’s University Belfast in Ireland, focusing primarily on time-resolved laser spectroscopic analysis of photophysical mechanisms. Dr. Coates also has experience in leading an industrial research and development team that was involved in developing novel DNA microarray technologies. Dr. Coates maintains overall product management responsibility for Andor's research and OEM camera/spectrograph business, encompassing imaging, spectroscopy, time-resolved, and X-ray product/market segments.

Moderator: Sean Sanders, Ph.D.

Science/AAAS
Washington, DC

Dr. Sanders did his undergraduate training at the University of Cape Town, South Africa, and his Ph.D. at the University of Cambridge, UK, supported by the Wellcome Trust. Following postdoctoral training at the National Institutes of Health and Georgetown University, Dr. Sanders joined TranXenoGen, a startup biotechnology company in Massachusetts working on avian transgenics. Pursuing his parallel passion for writing and editing, Dr. Sanders joined BioTechniques as an editor, before joining Science/AAAS in 2006. Currently Dr. Sanders is the Editor for Custom Publishing for the journal Science and Program Director for Outreach.

Visualizing Cell Signaling: Current Trends and New Technologies

If we had any decent or even adequate neurologists and hospitals this seminar would be required for all stroke medical staff to figure out how neurons signal each other to make neuroplasticity work. But alas, we have idiots instead.
http://webinar.sciencemag.org/webinar/archive/visualizing-cell-signaling
Techniques for the study of intracellular ions are used widely in biology, including for the tracking of calcium waves or ions affecting pH within living cells. The ability to monitor changes in intracellular ion concentrations over time is vital for our understanding of signaling and functional pathways in cellular systems. These pathways are central to many fundamental processes such as muscle contraction and synaptic nerve signal transmission. Ion channels that span the outer cell membrane open or close in response to extracellular and intracellular signals, potentially altering how the cell behaves. These fluctuations can be visualized and quantified using ratiometric microscopy and special fluorescent dyes designed to bind specific ions, such as the FURA-2 indicator dye specific to calcium ions. Changes in the photophysics of the dye as it binds to its target ion allows for quantitation of the bound and unbound ratio, and thus the concentration of the ion under investigation. This webinar will introduce the viewer to the current state of technology in this important field as well as cover the latest advances in microscopy for ion signaling research.
During the webinar, viewers will:

• Learn about current state-of-the-art ion signaling methodologies
• Discover what recent advances have been made in technologies for tracking ion changes, particularly calcium signaling
• Hear how experts in the field are applying these new technologies in the lab today
• Have the opportunity to ask questions of the expert panel live!

Speaker Bios

Mark Hollywood, Ph.D.

Dundalk Institute of Technology
Dundalk, Ireland

Dr. Hollywood undertook his Ph.D. at Queens University in Belfast, Ireland on the innervation of sheep mesenteric lymphatics. Following graduation in 1994, he commenced postdoctoral training in the Smooth Muscle Group and subsequently was offered a lecturer position in the Department of Physiology in 1995 and a senior lecturer post in 2001. In 2005, Dr. Hollywood together with his colleagues from the Smooth Muscle Group were recruited by Dundalk Institute of Technology to set up the Smooth Muscle Research Centre in Ireland, where he is currently a principal investigator. Dr. Hollywood’s research interests are focused on (1) developing novel ion channel modulators to treat overactive bladder and (2) examining the mechanisms underlying spontaneous activity in urethral pacemaker cells and how they modulate the bulk smooth muscle. His laboratory is currently developing a combined patch clamp/confocal microscopy system that will allow simultaneous imaging of whole-cell Ca2+ at frame rates in excess of 200 frames per second using back-illuminated EMCCD cameras, and enable correlation of this data to the resultant electrical activity observed in isolated urethral pacemaker cells.

C. Peter Bengtson, Ph.D.

University of Heidelberg
Heidelberg, Germany

Dr. Bengtson has a Ph.D. in neurophysiology from the Department of Physiology and Pharmacology at the University of Queensland, Australia.  He specializes in both patch clamp electrophysiology and wide-field microscopy from neurons in brain slices or dissociated cultures. He is currently a senior postdoctoral fellow in the Department of Neurobiology in the Interdisciplinary Center for Neuroscience (IZN) at Heidelberg University where he has worked for over a decade in the laboratory of Professor Hilmar Bading, primarily investigating the calcium signals and molecular mechanisms mediating long-term plasticity and memory.

Colin Coates, Ph.D.

Andor Technology
Belfast, Ireland

Dr. Coates holds a first-class degree in chemistry, with a postgraduate degree and postdoctoral research training from Queen’s University Belfast in Ireland, focusing primarily on time-resolved laser spectroscopic analysis of photophysical mechanisms. Dr. Coates also has experience in leading an industrial research and development team that was involved in developing novel DNA microarray technologies. Dr. Coates maintains overall product management responsibility for Andor's research and OEM camera/spectrograph business, encompassing imaging, spectroscopy, time-resolved, and X-ray product/market segments.

Moderator: Sean Sanders, Ph.D.

Science/AAAS
Washington, DC

Dr. Sanders did his undergraduate training at the University of Cape Town, South Africa, and his Ph.D. at the University of Cambridge, UK, supported by the Wellcome Trust. Following postdoctoral training at the National Institutes of Health and Georgetown University, Dr. Sanders joined TranXenoGen, a startup biotechnology company in Massachusetts working on avian transgenics. Pursuing his parallel passion for writing and editing, Dr. Sanders joined BioTechniques as an editor, before joining Science/AAAS in 2006. Currently Dr. Sanders is the Editor for Custom Publishing for the journal Science and Program Director for Outreach.

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