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Showing posts with label Chemical synapse. Show all posts
Showing posts with label Chemical synapse. Show all posts

Wednesday, November 16, 2011

Mimicking the Brain -- In Silicon: New Computer Chip Models How Neurons Communicate With Each Other at Synapses




For decades, scientists have dreamed of building computer systems that could replicate the human BRAIN's talent for learning new tasks.


Researchers have taken a major step toward that goal by designing a computer chip that mimics how the brain's neurons adapt in response to new information. (Credit: MIT)

MIT researchers have now taken a major step toward that goal by designing a computer chip that mimics how the brain's neurons adapt in response to new information. This phenomenon, known as plasticity, is believed to underlie many brain functions, including learning and memory.

With about 400 transistors, the silicon chip can simulate the activity of a single brain synapse -- a connection between two neurons that allows information to flow from one to the other. The researchers anticipate this chip will help neuroscientists learn much more about how the brain works, and could also be used in neural prosthetic devices such as artificial retinas, says Chi-Sang Poon, a principal research scientist in the Harvard-MIT Division of Health Sciences and Technology.

Poon is the senior author of a paper describing the chip in the Proceedings of the National Academy of Sciences the week of Nov. 14. Guy Rachmuth, a former postdoc in Poon's lab, is lead author of the paper. Other authors are Mark Bear, the Picower Professor of Neuroscience at MIT, and Harel Shouval of the University of Texas Medical School.

Modeling synapses

There are about 100 billion neurons in the brain, each of which forms synapses with many other neurons. A synapse is the gap between two neurons (known as the presynaptic and postsynaptic neurons). The presynaptic neuron releases neurotransmitters, such as glutamate and GABA, which bind to receptors on the postsynaptic cell membrane, activating ion channels. Opening and closing those channels changes the cell's electrical potential. If the potential changes dramatically enough, the cell fires an electrical impulse called an action potential.

All of this synaptic activity depends on the ion channels, which control the flow of charged atoms such as sodium, potassium and calcium. Those channels are also key to two processes known as long-term potentiation (LTP) and long-term depression (LTD), which strengthen and weaken synapses, respectively.

The MIT researchers designed their computer chip so that the transistors could mimic the activity of different ion channels. While most chips operate in a binary, on/off mode, current flows through the transistors on the new brain chip in analog, not digital, fashion. A gradient of electrical potential drives current to flow through the transistors just as ions flow through ion channels in a cell.

"We can tweak the parameters of the circuit to match specific ion channels," Poon says. "We now have a way to capture each and every ionic process that's going on in a neuron."

Previously, researchers had built circuits that could simulate the firing of an action potential, but not all of the circumstances that produce the potentials. "If you really want to mimic brain function realistically, you have to do more than just spiking. You have to capture the intracellular processes that are ion channel-based," Poon says.

The new chip represents a "significant advance in the efforts to incorporate what we know about the biology of neurons and synaptic plasticity onto CMOS [complementary metal-oxide-semiconductor] chips," says Dean Buonomano, a professor of neurobiology at the University of California at Los Angeles, adding that "the level of biological realism is impressive.

The MIT researchers plan to use their chip to build systems to model specific neural functions, such as the visual processing system. Such systems could be much faster than digital computers. Even on high-capacity computer systems, it takes hours or days to simulate a simple brain circuit. With the analog chip system, the simulation is even faster than the biological system itself.

Another potential application is building chips that can interface with biological systems. This could be useful in enabling communication between neural prosthetic devices such as artificial retinas and the brain. Further down the road, these chips could also become building blocks for artificial intelligence devices, Poon says.

Debate resolved

The MIT researchers have already used their chip to propose a resolution to a longstanding debate over how LTD occurs.

One theory holds that LTD and LTP depend on the frequency of action potentials stimulated in the postsynaptic cell, while a more recent theory suggests that they depend on the timing of the action potentials' arrival at the synapse.

Both require the involvement of ion channels known as NMDA receptors, which detect postsynaptic activation. Recently, it has been theorized that both models could be unified if there were a second type of receptor involved in detecting that activity. One candidate for that second receptor is the endo-cannabinoid receptor.

Endo-cannabinoids, similar in structure to marijuana, are produced in the brain and are involved in many functions, including appetite, pain sensation and memory. Some neuroscientists had theorized that endo-cannabinoids produced in the postsynaptic cell are released into the synapse, where they activate presynaptic endo-cannabinoid receptors. If NMDA receptors are active at the same time, LTD occurs.

When the researchers included on their chip transistors that model endo-cannabinoid receptors, they were able to accurately simulate both LTD and LTP. Although previous experiments supported this theory, until now, "nobody had put all this together and demonstrated computationally that indeed this works, and this is how it works," Poon says.

Monday, June 27, 2011

In Search of the Memory Molecule, Researchers Discover Key Protein Complex



Have a tough time remembering where you put your keys, learning a new language or recalling names at a cocktail party? New research from the Lisman Laboratory at Brandeis University points to a molecule that is central to the process by which memories are stored in the brain.
The CaMKII molecule has 12 lobes (6 are shown here), 
each of which has enzymatic activity. This molecule can 
bind to the NMDA receptor, forming a complex. The 
number of such complexes at the synapse may increase 
the amount of memory that can be stored. 
(Credit: Neal Waxham)

A paper published in the June 22 issue of the Journal of Neuroscience describes the new findings.

The brain is composed of neurons that communicate with each other through structures called synapses, the contact point between neurons. Synapses convey electrical signals from the "sender" neuron to the "receiver" neuron. Importantly, a synapse can vary in strength; a strong synapse has a large effect on its target cell, a weak synapse has little effect.

New research by John Lisman, professor of biology and the Zalman Abraham Kekst chair in neuroscience, helps explain how memories are stored at synapses. His work builds on previous studies showing that changes in the strength of these synapses are critical in the process of learning and memory.

"It is now quite clear that memory is encoded not by the change in the number of cells in the brain, but rather by changes in the strength of synapses," Lisman says. "You can actually now see that when learning occurs, some synapses become stronger and others become weaker."

But what is it that controls the strength of a synapse?

Lisman and others have previously shown that a particular molecule called Ca/calmodulin-dependent protein kinase II (CaMKII) is required for synapses to change their strength. Lisman's team is now showing that synaptic strength is controlled by the complex of CaMKII with another molecule called the NMDAR-type glutamate receptor (NMDAR). His lab has discovered that the amount of this molecular complex (called the CaMKII/NMDAR complex) actually determines how strong a synapse is, and, most likely, how well a memory is stored.

"We're claiming that if you looked at a weak synapse you'd find a small number of these complexes, maybe one," says Lisman. "But at a strong synapse you might find many of these complexes."

A key finding in their experiment used a procedure that reduced the amount of this complex. When the complex was reduced, the synapse became weaker. This weakening was persistent, indicating that the memory stored at that synapse was erased.



The experiments were done using small slices of rat hippocampus, the part of the brain crucial for memory storage.

"We can artificially induce learning-like changes in the strength of synapses because we know the firing pattern that occurs during actual learning in an animal," Lisman says.

To prove their hypothesis, he explained, his team first strengthened the synapse, eventually saturating it to the point where no more learning or memory could take place. They then added a chemical called CN-19 to the synapse, which they suspected would dissolve the CaMKII/NMDAR complex. As predicted, it did in fact make the synapse weaker, suggesting the loss of memory.

A final experiment, says Lisman, was the most exciting: They started out by making the synapse so strong that it was "saturated," as indicated by the fact that no further strengthening could be induced. They then "erased" the memory with the chemical CN-19. If the "memory" was really erased, the synapse should no longer be saturated. To test this hypothesis, Lisman's team again stimulated the synapse and found that it could once again "learn." Taken together, these results demonstrated the ability of CN19 to erase the memory of a synapse -- a critical criterion for establishing that the CaMKII/NMDAR complex is the long sought memory storage molecule in the brain.

Lisman's team used CN19 due to previous studies, which indicate that the chemical could affect the CaMKII/NMDAR complex. Lisman's team wanted to show that CN19 would decrease the complex in living cells. Several key control experiments proved this to be the case.

"Most people accept that the change in the synapses that you can see under the microscope is the mechanism that actually occurs during learning," says Lisman. "So this paper will have a lot of impact -- but in science you still have to prove things, so the next step would be to try this in an actual animal and see if we can make it forget something it has previously learned."

Lisman says that if memory is understood at the biochemical level, the impact will be enormous.

"You have to understand how memory works before you can understand the diseases of memory."

Lisman assembled a large team to undertake this complex research. A key collaborator was Magdalena Sanhueza, who once worked with Dr. Lisman at Brandeis, and her student, German Fernandez-Villalobos, both now of the University of Chile, Department of Biology and Ulli Bayer of the University of Colorado Denver School of Medicine, Department of Pharmacology, who developed CN19, a particular form that could actually enter neurons.

Others involved include Nikolai Otmakhov and Peng Zhang from Brandeis and Gyulnara Kasumova, who worked in the Lisman laboratory for several years as an undergraduate. An additional group contributing to the work was that of Johannes Hell, Professor of Pharmacology at the UC Davis School of Medicine. He and his student, Ivar S. Stein, used immunoprecipitation methods to actually show that the CN19 had dissolved the CaMKII/NMDAR complex.

Sunday, January 24, 2010

Neuron Connections Seen in 3-D


A team of researchers from the Max Planck Institute of Biochemistry, in Germany, led by the Spanish physicist Rubén Fernández-Busnadiego, has managed to obtain 3D images of the vesicles and filaments involved in communication between neurons. The method is based on a novel technique in electron microscopy, which cools cells so quickly that their biological structures can be frozen while fully active.

This three-dimensional visualization of synapses shows the tomography mail synaptic vesicles (yellow), cell membrane (purple), connectors between vesicles (red), filaments that anchor the vesicles to the cell membrane (blue), microtubule (dark green), material synaptic space (light green) and postsynaptic density (orange). (Credit: Fernández-Busnadiego et al.)

"We used electron cryotomography, a new technique in microscopy based on ultra-fast freezing of cells, in order to study and obtain three-dimensional images of synapsis, the cellular structure in which the communication between neurons takes place in the brains of mammals" Rubén Fernández-Busnadiego, lead author of the study which features on the front cover of this month's Journal of Cell Biology and a physicist at the Max Planck Institute of Biochemistry, in Germany, said.

Sunday, September 13, 2009

Star-shaped Cells In Brain Help With Learning


Every movement and every thought requires the passing of specific information between networks of nerve cells. To improve a skill or to learn something new entails more efficient or a greater number of cell contacts. Scientists at the Max Planck Institute of Neurobiology in Martinsried can now show, together with an international team of researchers, that certain cells in the brain, the astrocytes, actively influence this information exchange.
Some contact points between nerve cells (red) are surrounded by star-shaped cells known as astrocytes (green). It is now shown that via ephrinA3/EphA4 interactions, astrocytes influence the communication between nerve cells by removing the transmitter molecule glutamate. 
This so far unknown activity also has implications for the ability to learn. 
(Credit: Max Planck Institute of Neurobiology / Schorner, Klein & Paixão)

Until now, astrocytes were thought to have their main role in the development and nutrition of the brain's nerve cells. The new findings improve our comprehension of how the brain learns and remembers. They could also aid in the basic research of diseases such as epilepsy and the amyotrophic lateral sclerosis (ALS).
To live is to learn: Even fruit flies can learn to avoid detrimental odors and also in humans, most abilities are based on what we learn through practice and experience. Thus we are able to perform both fundamental processes such as walking and speaking and also master complex tasks such as logical reasoning and social interactions.