Neuroscience  

Scientists have observed and measured synaptic transmission in a live animal for the first time, using optogenetics.

Neurons, the cells of the nervous system, communicate by transmitting chemical signals to each other through junctions called synapses. This "synaptic transmission" is critical for the brain and the spinal cord to quickly process the huge amount of incoming stimuli and generate outgoing signals.

Studying synaptic transmission in living animals is however very difficult, and researchers have to use artificial conditions that don't capture the real-life environment of neurons.

Now, scientists at the École Polytechnique Fédérale de Lausanne have observed and measured synaptic transmission in a live animal for the first time, using a new approach that combines genetics with the physics of light. Their breakthrough work is published in Neuron.

Aurélie Pala and Carl Petersen at EPFL's Brain Mind Institute used a novel technique, "optogenetics", that has been making significant inroads in the field of neuroscience in the past ten years. This method uses light to precisely control the activity of specific neurons in living, even moving, animals in real time. Such precision is critical in being able to study the hundreds of different neuron types, and understand higher brain functions such as thought, behavior, language, memory - or even mental disorders.

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Optogenetics works by inserting the gene of a light-sensitive protein into live neurons, from a single cell to an entire family of them. The genetically modified neurons then produce the light-sensitive protein, which sits on their outside, the membrane. There, it acts as an electrical channel - something like a gate. When light is shone on the neuron, the channel opens up and allows electrical ions to flow into the cell; a bit like a battery being charged by a solar cell.

The addition of electrical ions changes the voltage balance of the neuron, and if the optogenetic stimulus is sufficiently strong it generates an explosive electrical signal in the neuron. And that is the impact of optogenetics: controlling neuronal activity by switching a light on and off.

"This is a proof-of-concept study. Nonetheless, we think that we can use optogenetics to put together a larger picture of connectivity between other types of neurons in other areas of the brain."

Pala used optogenetics to stimulate single neurons of anesthetized mice and see if this approach could be used to record synaptic transmissions. The neurons she targeted were located in a part of the mouse's brain called the barrel cortex, which processes sensory information from the mouse's whiskers.

When Pala shone blue light on the neurons that contained the light-sensitive protein, the neurons activated and fired signals. At the same time, she measured electrical signals in neighboring neurons using microelectrodes that can record small voltage changes across a neuron's membrane.

Using these approaches, the researchers looked at how the light-sensitive neurons connected to some of their neighbors: small, connector neurons called "interneurons". In the brain, interneurons are usually inhibitory: when they receive a signal, they make the next neuron down the line less likely to continue the transmission.

The researchers recorded and analyzed synaptic transmissions from light-sensitive neurons to interneurons. In addition, they used an advanced imaging technique (two-photon microscopy) that allowed them to look deep into the brain of the live mouse and identify the type of each interneuron they were studying. The data showed that the neuronal transmissions from the light-sensitive neurons differed depending on the type of interneuron on the receiving end.

"This is a proof-of-concept study," says Aurélie Pala, who received her PhD for this work. "Nonetheless, we think that we can use optogenetics to put together a larger picture of connectivity between other types of neurons in other areas of the brain."

The scientists are now aiming to explore other neuronal connections in the mouse barrel cortex. They also want to try this technique on awake mice, to see how switching neuronal activity on and off with a light can affect higher brain functions.


SOURCE  École Polytechnique Fédérale de Lausanne via EurekAlert

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 Medicine  

Cutting edge medical advancements are helping to detect diseases early and provide a tailored treatment that is highly effective in treating and curing illness. Here is a glimpse into the high-tech health care resulting from the newest in medical technology.

Not long ago, AIDS was considered as an untreatable disease. Cancer was considered as a disease with low chances of survival. Elders living alone had great difficulties reaching for help. The difficulties associated with monitoring high-risk patients 24/7 often led to their death. All these are changing now due to the emergence high-tech health care. Recent developments in patient surveillance and tracking are helping to closely monitor the high-risk patients. Advancements in genome sequencing and Pharmacogenomics are helping to detect diseases early and provide a tailored treatment that is highly effective in curing diseases, including cancer. Here is a glimpse into the high-tech health care resulting from the advancements in medical technology.

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Sensors, Wearable Devices, and Remote Monitoring Tools

New wearable medical devices can now detect and send alerts when a patient falls down. Bandages can detect infections by monitoring the pH level. Patients at high risk can be fitted with devices such as a cardiac cast that can monitor the heartbeat and send data to a monitoring center. Digestible sensors can transmit information about the human body, including organs. Patients can now stay at home rather than in the hospital, helping to cut down the hospital cost and the readmission requirements.

Robotic Surgery, Drug Discovery

A surgeon can now perform advanced surgeries by using a robotic hand that can reach through a small cut made in the body. This technique is used for several complex surgical tasks, including coronary artery bypass, kidney transplant, and gallbladder removal. Researchers can now use Hudson products like robotic assay screening and development system for drug discovery using different detection methods such as enzyme-linked immunoabsorption, reporter gene luminescence, and fluorescence energy transfer. Robotic systems can also be used to determine the pharmaceutical profile of a patient.

3D Printing

Biological materials such as blood vessels, heart tissues, and embryonic stem cells can now be printed using 3D printers. 3D printing has also been used for patching a broken heart as well as replacing organs. There have been advances in developing skins for patients by printing skin cells using this technique.

Optogenetics

Advances in neuroscience have made it possible for scientists to control the neurons in the brain. This technique is used for understanding the cause and curing different mental disorders such as Parkinson’s disease and schizophrenia.

There are greater benefits to humankind due to the advancements in medical technology. The high tech health care is ascending, and is helping to achieve things that were considered impossible not long ago. The emergence of big data analytics in discovering medical patterns is helping to understand diseases and treatments better. Use of robotics in surgical and drug discovery area seems very promising. Health monitoring devices are now even being integrated into smartphones, making the medical technology go mainstream. As medical tech grows, so will our quality of life.

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About the Author - Anica is a freelance writer and web enthusiast. You can read some of her published work at her Google+ page.

 Neuroscience  

Researchers have found that the brain's wiring is more complex than expected – one set of neural wires can trigger different reactions, depending on how it fires. The work opens new questions for scientists trying to map the brain's connections.

Scientists at Stanford's Bio-X have raised an entirely new set of questions when they sought answers about connections between two brain regions.

"There's a lot of excitement about being able to make a map of the brain with the idea that if we could figure out how it is all connected we could understand how it works,"  researcher Joanna Mattis said. "It turns out it's so much more dynamic than that."

Mattis is a co-first author on a paper describing the work published recently in the Journal of Neuroscience. Julia Brill, then a postdoctoral scholar, was the other co-first author.

Mattis had been a graduate student in the lab of Karl Deisseroth, professor of bioengineering and of psychiatry and behavioral sciences, where she helped work on a new technique called optogenetics. That technique allows neuroscientists to selectively turn parts of the brain on and off to see what happens. She wanted to use optogenetics to understand the wiring of a part of the brain involved in spatial memory – it's what makes a mental map of your surroundings as you explore a new city, for example.

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Scientists already knew that when an animal explores habitats, two parts of the brain are involved in the initial exploring phase and then in solidifying a map of the environment – the hippocampus and the septum.

When an animal is exploring an environment, the neurons in the hippocampus fire slow signals to the septum, essentially telling the septum that it's busy acquiring information. Once the animal is done exploring, those same cells fire off intense signals letting the septum know that it's now locking that information into memory. The scientists call this phase consolidation. The septum uses that information to then turn around and regulate other signals going into the hippocampus.

"I wanted to study the hippocampus because on the one hand so much was already known – there was already this baseline of knowledge to work off of. But then the question of how the hippocampus and septum communicate hadn't been accessible before optogenetics," Mattis said.

Neural wiring diagrams are even more complex than initially speculated according to new research

Neurons in the hippocampus were known to fire in a rhythmic pattern, which is a particular expertise of John Huguenard, a professor of neurology. Mattis obtained an interdisciplinary fellowship through Stanford Bio-X, which allowed her to combine the Deisseroth lab's expertise in optogenetics with the rhythmic brain network expertise of Julia Brill from the Huguenard lab.

"There's a lot of excitement about being able to make a map of the brain with the idea that if we could figure out how it is all connected we could understand how it works."

Mattis and Brill used optogenetics to prompt neurons of the hippocampus to mimic either the slow firing characteristic of information acquisition or the rapid firing characteristic of consolidation. When they mimicked the slow firing they saw a quick reaction by cells in the septum. When they mimicked the fast consolidation firing, they saw a much slower response by completely different cells in the septum.

Same set of wires – different outcome. That's like turning on different lights depending on how hard you flip the switch. "This illustrates how complex the brain is," Mattis said.

This research has raised a whole new set of questions, Mattis said. They more or less understand the faster reaction, but what is causing the slower reaction? How widespread is this phenomenon in the brain?

"The other big picture thing that we opened up but didn't answer is: How can you then tie this back to the circuit overall and learning memory?" Mattis said. "Those would be exciting things to follow up on for future projects."


SOURCE  Stanford

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 Neuroscience  

Optogenetics pioneer, Ed Boyden recently sat down for a discussion on the importance of neuroscience research on the Singularity 1 on 1 podcast.

One of the main presenters at last year’s Global Future 2045 Conference in New York was neuroscientist, Dr. Ed Boyden. Boyden’s impressive work in neuroscience in general and optogenetics in particular, may have profound implications it would have on our ability to understand and manipulate the brain.

Recently Nikola Danaylov interviewed Boyden on the podcast Singularity 1 on 1.

"Our approach is very much focused on the technologies that will allow us to numerate, and describe the mechanistic processes through which neural circuits interact."

During the conversation with Boyden, the pair covered a variety of topics such as: his interesting career path from chemistry to physics to electrical engineering and into neuroscience; the loop of understanding and why the brain is where we need to go; and the importance of philosophy.

Boyden also covers his work in optogenetics and whether the brain is a classical computer or not. A major goal of Boyden’s current work is to manipulate individual nerve cells using light. To do this, he takes advantage of naturally occurring light-sensitive proteins from various microorganisms, which can be artificially expressed in brain cells using genetic technology. By controlling these proteins with an implanted fiber-optic device, Boyden is developing on/off switches for brain activity. This will be a powerful way to test theories of brain function in experimental animals, and could also open the door to new clinical therapies for conditions such as epilepsy, Parkinson’s disease, or blindness.

The pair discuss the Penrose-Hameroff theory of consciousness; and the Human Brain Project.

Boyden and Danaylov also touch on Randal Koene's Whole Brain Emulation project; the definition and importance of consciousness; neuroplasticity and Norman Doidge’s The Brain That Changes Itself. They also talk about free will and mind-uploading.

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Boyden is Associate Professor of Biological Engineering and Brain and Cognitive Sciences, at the MIT Media Lab and the MIT McGovern Institute. He leads the Synthetic Neurobiology Group, which develops tools for analyzing and engineering the circuits of the brain. These technologies, created often in interdisciplinary collaborations, include ‘optogenetic’ tools, which enable the activation and silencing of neural circuit elements with light, 3-D microfabricated neural interfaces that enable control and readout of neural activity, and robotic methods for automatically recording intracellular neural activity and performing single-cell analyses in the living brain. He has launched an award-winning series of classes at MIT that teach principles of neuroengineering, starting with basic principles of how to control and observe neural functions, and culminating with strategies for launching companies in the nascent neurotechnology space. He also co-directs the MIT Center for Neurobiological Engineering, which aims to develop new tools to accelerate neuroscience progress.

Amongst other recognitions, he has received the Jacob Heskel Gabbay Award (2013), the Grete Lundbeck European “Brain” Prize, the largest brain research prize in the world (2013), the Perl/UNC Neuroscience Prize (2011), the A F Harvey Prize (2011), and the Society for Neuroscience Research Award for Innovation in Neuroscience (RAIN) Prize (2007). He has also received the NIH Director’s Pioneer Award (2013), the NIH Director’s Transformative Research Award (twice, 2012 and 2013), and the NIH Director’s New Innovator Award (2007), as well as the New York Stem Cell Foundation-Robertson Investigator Award (2011) and the the Paul Allen Distinguished Investigator Award in Neuroscience (2010). He was also named to the World Economic Forum Young Scientist list (2013), the Wired Smart List “50 People Who Will Change the World” (2012), the Technology Review World’s “Top 35 Innovators under Age 35″ list (2006), and his work was included in Nature Methods “Method of the Year” in 2010.

His group has hosted hundreds of visitors to learn how to use neurotechnologies, and he also regularly teaches at summer courses and workshops in neuroscience, as well as delivering lectures to the broader public at TED and at the World Economic Forum. Ed received his Ph.D. in neurosciences from Stanford University as a Hertz Fellow, where he discovered that the molecular mechanisms used to store a memory are determined by the content to be learned. Before that, he received three degrees in electrical engineering, computer science, and physics from MIT. He has contributed to over 300 peer-reviewed papers, current or pending patents, and articles, and has given over 240 invited talks on his group’s work.



SOURCE  Singularity Weblog

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 Neuroscience  

Using optogenetics, researchers have mapped the signaling of touch sensations directly from cells into the skin.  The work could lead to the development of artificial skin and smarter prosthetics.

In a study published online in the journal Nature, a team of Columbia University Medical Center researchers led by Ellen Lumpkin, PhD, associate professor of somatosensory biology, solve an age-old mystery of touch: how cells just beneath the skin surface enable us to feel fine details and textures.

Touch is the last frontier of sensory neuroscience. The cells and molecules that initiate vision—rod and cone cells and light-sensitive receptors—have been known since the early 20th century, and the senses of smell, taste, and hearing are increasingly understood. But almost nothing is known about the cells and molecules responsible for initiating our sense of touch.

"These experiments are the first direct proof that Merkel cells can encode touch into neural signals that transmit information to the brain about the objects in the world around us."

This study is the first to use optogenetics—a new method that uses light as a signaling system to turn neurons on and off on demand—on skin cells to determine how they function and communicate.

The team showed that skin cells called Merkel cells can sense touch and that they work virtually hand in glove with the skin’s neurons to create what we perceive as fine details and textures.

“These experiments are the first direct proof that Merkel cells can encode touch into neural signals that transmit information to the brain about the objects in the world around us,” Dr. Lumpkin said.

The findings not only describe a key advance in our understanding of touch sensation, but may stimulate research into loss of sensitive-touch perception.

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Several conditions—including diabetes and some cancer chemotherapy treatments, as well as normal aging—are known to reduce sensitive touch. Merkel cells begin to disappear in one’s early 20s, at the same time that tactile acuity starts to decline. “No one has tested whether the loss of Merkel cells causes loss of function with aging—it could be a coincidence—but it’s a question we’re interested in pursuing,” Dr. Lumpkin said.

In the future, these findings could inform the design of new “smart” prosthetics that restore touch sensation to limb amputees, as well as introduce new targets for treating skin diseases such as chronic itch.

The study was published in conjunction with a second study by the team done in collaboration with the Scripps Research Institute. The companion study identifies a touch-activated molecule in skin cells, a gene called Piezo2, whose discovery has the potential to significantly advance the field of touch perception.

“The new findings should open up the field of skin biology and reveal how sensations are initiated,” Dr. Lumpkin said. Other types of skin cells may also play a role in sensations of touch, as well as less pleasurable skin sensations, such as itch. The same optogenetics techniques that Dr. Lumpkin’s team applied to Merkel cells can now be applied to other skin cells to answer these questions.

“It’s an exciting time in our field because there are still big questions to answer, and the tools of modern neuroscience give us a way to tackle them,” she said.




SOURCE  Columbia University Medical Center

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 Bionics  

In a recent TED Talk, Grégoire Courtine shows a new method -- combining drugs, electrical stimulation and a robot -- that could re-awaken the neural pathways and help the body learn again to move on its own.

A spinal cord injury can sever the communication between your brain and your body, leading to paralysis. Fresh from his lab, Grégoire Courtine shows a new method -- combining drugs, electrical stimulation and a robot -- that could re-awaken the neural pathways and help the body learn again to move on its own. See how it works, as a paralyzed rat becomes able to run and navigate stairs.

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Courtine and his team are are developing multifaceted neuroprosthetic systems, robotic interfaces and advanced neurorehabilitation procedures that are combined with neuroregenerative interventions. Using genetically modified mice, optogenetics, and novel viral tools, they also seek to uncover the neural mechanisms underlying the control of locomotion in intact animals, as well as the processes that reestablish motor functions after neuromotor disorders.

Courtine's work has led him to develop what he calls personalized neuroprosthetics.  Recently, the team published this research in the journal Science.  According to the reearchers, decades of technological developments have populated the field of neuroprosthetics with multiple replacement strategies, neuromodulation therapies, and rehabilitation procedures to improve the quality of life for individuals with neuromotor disorders.

Image Source: Courtine/TED

Despite the few but impressive clinical successes, and multiple breakthroughs in animal models, neuroprosthetic technologies for humans remain mainly confined to the laboratory. The team ties the core principles and latest achievements in neuroprosthetics, but also address the challenges that lie along the path toward actual application.  Courtine proposes a pragmatic framework to personalize neurotechnologies and rehabilitation for patient-specific impairments to achieve the timely dissemination of neuroprosthetic medicine.

SOURCE  TED

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 Neuroscience  

Researchers are using the fruit fly to discover how the brain integrates multiple signals to identify one unique smell. It's work that has broader implication for how flies -- and ultimately, people -- learn.

Think of the smell of an orange, a lemon, and a grapefruit. Each has strong acidic notes mixed with sweetness. And yet each fresh, bright scent is distinguishable from its relatives. These fruits smell similar because they share many chemical compounds. How, then does the brain tell them apart? How does the brain remember a complex and often overlapping chemical signature as a particular scent?

Researchers at Cold Spring Harbor Laboratory (CSHL) are using the fruit fly to discover how the brain integrates multiple signals to identify one unique smell. It's work that has broader implication for how flies – and ultimately, people – learn. In work published  in Nature Neuroscience, a team led by Associate Professor Glenn Turner describes how a group of neurons in the fruit fly brain recognize multiple individual chemicals in combination in order to define, or remember, a single scent.

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The olfactory system of a fruit fly begins at the equivalent of our nose, where a series of neurons sense and respond to very specific chemicals. These neurons pass their signal on to a group of cells called projection neurons. Then the signal undergoes a transformation as it is passed to a body of neurons in the fly brain called Kenyon cells.

Kenyon cells have multiple, extremely long protrusions that grasp the projection neurons with a claw-like structure. Each Kenyon cell claw is wrapped tightly around only one projection neuron, meaning that it receives a signal from just one type of input. In addition to their unique structure, Kenyon cells are also remarkable for their selectivity. Because they're selective, they aren't often activated. Yet little is known about what in fact makes them decide to fire a signal.

Turner and colleague Eyal Gruntman, who is lead author on their new paper, used cutting-edge microscopy to explore the chemical response profile for multiple claws on one Kenyon cell. They found that each claw, even on a single Kenyon cell, responded to different chemicals. Additional experiments using light to stimulate individual neurons (a technique called optogenetics) revealed that single Kenyon cells were only activated when several of their claws were simultaneously stimulated, explaining why they so rarely fire. Taken together, this work explains how individual Kenyon cells can integrate multiple signals in the brain to "remember" the particular chemical mixture as a single, distinct odor .

Turner will next try to determine "what controls which claws are connected," which will provide insight into how the brain learns to assign a specific mix of chemicals as defining a particular scent. But beyond simple odor detection, the research has more general implications for learning. For Turner, the question driving his work forward is: what in the brain changes when you learn something?


SOURCE  Cold Springs Harbor Laboratory

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 Neuroscience  

A new study, which uses technologies highlighted in the US Brain Initiative, suggests that faulty wiring in certain brain cells could interfere with hunger or satiety cues and contribute to human eating disorders, leading people to eat even when they are full or to avoid food when they are hungry.

Sixty years ago scientists could electrically stimulate a region of a mouse’s brain causing the mouse to eat, whether hungry or not. Now researchers from UNC School of Medicine have pinpointed the precise cellular connections responsible for triggering that behavior.

The finding, published in the journal Science, lends insight into a cause for obesity and could lead to treatments for anorexia, bulimia nervosa, and binge eating disorder, the most prevalent eating disorder in the United States.

“The study underscores that obesity and other eating disorders have a neurological basis,” said senior study author Garret Stuber, PhD, assistant professor in the department of psychiatry and department of cell biology and physiology. He’s also a member of the UNC Neuroscience Center. “With further study, we could figure out how to regulate the activity of cells in a specific region of the brain and develop treatments.”

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Back in the 1950s, when scientists electrically stimulated a region of the brain called the lateral hypothalamus, they knew that they were stimulating many different types of brain cells. Stuber wanted to focus on one cell type — gaba neurons in the bed nucleus of the stria terminalis, or BNST. The BNST is an outcropping of the amygdala, the part of the brain associated with emotion. The BNST also forms a bridge between the amygdala and the lateral hypothalamus, the brain region that drives primal functions such as eating, sexual behavior, and aggression.

The BNST gaba neurons have a cell body and a long strand with branched synapses that transmit electrical signals into the lateral hypothalamus. Stuber and his team wanted to stimulate those synapses by using an optogenetic technique, an involved process that would let him stimulate BNST cells simply by shining light on their synapses.

Typically, brain cells don’t respond to light. So Stuber’s team used genetically engineered proteins — from algae — that are sensitive to light and used genetically engineered viruses to deliver them into the brains of mice. Those proteins then get expressed only in the BNST cells, including in the synapses that connect to the hypothalamus.

His team then implanted fiber optic cables in the brains of these specially-bred mice, and this allowed the researchers to shine light through the cables and onto BNST synapses. As soon as the light hit BNST synapses the mice began to eat voraciously even though they had already been well fed. Moreover, the mice showed a strong preference for high-fat foods.

“They would essentially eat up to half their daily caloric intake in about 20 minutes,” Stuber said. “This suggests that this BNST pathway could play a role in food consumption and pathological conditions such as binge eating.”

Stimulating the BNST also led the mice to exhibit behaviors associated with reward, suggesting that shining light on BNST cells enhanced the pleasure of eating. On the flip side, shutting down the BNST pathway caused mice to show little interest in eating, even if they had been deprived of food.

 “We were able to really home in on the precise neural circuit connection that was causing this phenomenon that’s been observed for more than 50 years,” Stuber said.

The study, which uses technologies highlighted in the new National Institutes of Health Brain Initiative, suggests that faulty wiring in BNST cells could interfere with hunger or satiety cues and contribute to human eating disorders, leading people to eat even when they are full or to avoid food when they are hungry. Further research is needed to determine whether it would be possible to develop drugs that correct a malfunctioning BNST circuit. Brain

“We want to actually observe the normal function of these cell types and how they fire electrical signals when the animals are feeding or hungry,” Stuber said. “We want to understand their genetic characteristics – what genes are expressed. For example, if we find cells that become really activated after binge eating, can we look at the gene expression profile to find out what makes those cells unique from other neurons.”

And that, Stuber said, could lead to potential targets for drugs to treat certain populations of patients with eating disorders.



SOURCE  UNC Chapel Hill

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 Brain Mapping  

Scientists at Yale University have used a new protein, called ArcLight, to watch nerve cell electricity in a live fly brain. This new tool of optogenetics allows researchers to watch, in real time, the cell’s electrical activity.

Scientists have used fruit flies to show for the first time that a new class of genetically engineered proteins can be used to watch electrical activity in individual brain cells in live brains. The results, published in Cell, suggest these proteins may be a promising new tool for mapping brain cell activity in multiple animals.

 The research also has potential applications for studying how neurological disorders disrupt normal nerve cell signaling. Understanding brain cell activity is a high priority of President Obama’s Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative.

Brain cells use electricity to control thoughts, movements and senses. Ever since the late nineteenth century, when Dr. Luigi Galvani induced frog legs to move with electric shocks, scientists have been trying to watch nerve cell electricity to understand how it is involved in these actions.

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Usually they directly mo nitor electricity with cumbersome electrodes or toxic voltage-sensitive dyes, or indirectly with calcium detectors. This study, led by Michael Nitabach, Ph.D., J.D., and Vincent Pieribone, Ph.D., at the Yale School of Medicine, New Haven, CT, shows that a class of proteins, called genetically encoded fluorescent voltage indicators (GEVIs), may allow researchers to watch nerve cell electricity in a live animal.

Dr. Pieribone and his colleagues helped develop ArcLight, the protein used in this study. ArcLight fluoresces, or glows, as a nerve cell’s voltage changes and enables researchers to watch, in real time, the cell’s electrical activity.

“Electrical signals are the language the nervous system uses to transmit information,” says Pieribone, professor of cellular and molecular physiology and of neurobiology. “Now we can look at this electrical information optically and non-invasively.”
 In this study, Dr. Nitabach and his colleagues engineered fruit flies to express ArcLight in brain cells that control the fly’s sleeping cycle or sense of smell. Initial experiments in which the researchers simultaneously watched brain cell electricity with a microscope and recorded voltage with electrodes showed that ArcLight can accurately monitor electricity in a living brain.

Further experiments showed that ArcLight illuminated electricity in parts of the brain that were previously inaccessible using other techniques. Finally, ArcLight allowed the researchers to watch brain cells spark and fire while the flies were awakening and smelling. These results suggest that in the future neuroscientists may be able to use ArcLight and similar GEVIs in a variety of ways to map brain cell circuit activity during normal and disease states.

"Seeing electrical activity in the brain directly is a long-standing dream that now seems tangible,” says Gero A. Miesenböck, M.D., director of the Center for Neuronal Circuits and Behavior at the University of Oxford and a former associate professor of cell biology at the School of Medicine.

While at Yale, Miesenböck pioneered optogenetics, the use of light to control behavior via genetically encoded photosensitive components in neurons. What Pieribone, Nitabach, and colleagues have done is the flip side of optogenetics, using light, or fluorescence, to visualize neural activity, which Miesenböck calls “an important milestone.” While ArcLight is the most favorable GEVI available at the moment, says Miesenböck, a big challenge still remains in improving optical instrumentation for even better localization of neural signals in both space and time.

In the two videos below, fruit flies are shown without and with the ArcLight protein modification. The scientists simultaneously watched ArcLight glow and recorded the electricity of a brain cell with an electrode. The red and green traces at the bottom show that ArcLight glowed in parallel with changes in the cell's electricity (white trace).





SOURCE  Yale University

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 Neuroscience  

The film 'Inception' may be getting closer to becoming real. Using optogenetics, researchers have planted false memories into the minds of mice. The work potentially illuminates the mechanisms underlying the human phenomenon of “recalling” experiences that never occurred.

Researchers at the RIKEN-MIT Center for Neural Circuit Genetics and MIT's Picower Institute for Learning and Memory have implanted false memories into mice, potentially illuminating the mechanisms underlying the human phenomenon of "recalling" experiences that never occurred.

In previous work, the researchers had detected a single memory in the brain, genetically tagged the brain cells housing that memory with a light-sensitive protein, and flickered pulses of light to "turn on" the memory at any given moment. The latest work, published in the journal Science, tinkers with that memory to change its contents—in essence, creating a false memory.

This work in mice may lead to new understanding of how and why humans form false memories, and may eventually help physically pinpoint where memories are formed in the brain.

Our memories are stored in assemblies of neurons, called engram-bearing cells, that can be compared to toy building blocks. When we recall a sequence of events, our brains reconstruct the past from these bricks of data, but the very act of accessing a memory modifies and distorts it.

When the influence of external sources is, it's not surprising that memory can be notoriously unreliable, yet inaccurate memories can have dire consequences. For instance, most three-quarters of the first 250 people to be exonerated by DNA evidence in the US were victims of faulty eyewitness testimony.

"Human studies utilizing behavioral and fMRI (functional magnetic resonance imaging) techniques have not been able to delineate the hippocampal subregions and circuits responsible for generating false memories," said study author Susumu Tonegawa, Picower Professor of Biology and Neuroscience and director of the RIKEN-MIT Center for Neural Circuit Genetics.

"Our experiments provide the first animal model in which false and genuine memories can be investigated at the memory engram level."

Dr Tonegawa and his team successfully created a false memory in genetically modified mice by manipulating engram-bearing cells in the hippocampus, a seahorse-shaped part of the brain known to play a role in forming and storing memories of experiences.

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Optogenetics, which are transforming neuroscience, were used to locate and chemically label neurons as well as make them susceptible to activation by blue light transmitted by a fiber optic cable in the mouse brain. With these techniques the researchers were able to identify and chemically label which neurons were involved in forming the initial memory of the first environment, and to reactivate the labeled cells a day later with light.

The researchers zeroed in on the animals' brain cells that represented the safe environment of a setting, Box A, and programmed those cells to respond to pulses of light. Next, they placed the animals in a completely different environment—Box B—and pulsed light into their brains to reactivate the memory of Box A.

They then gave the animals mild foot shocks, creating a negative association between the light-reactivated memory of Box A and the foot shocks, which mice find highly aversive.

When the animals were placed back in Box A—the safe environment in which nothing averse had ever happened—the researchers found that the animals now displayed heightened fear responses. In addition, after placing the animals in yet another new environment while shining light on the hippocampal cells that had been artificially associated with fear, the researchers found they could reactivate the false fear memory at will.

"Humans are highly imaginative animals. Just like our mice, an aversive or appetitive event could be associated with a past experience one may happen to have in mind at that moment, hence a false memory is formed," said Tonegawa.

The results are “really mind-blowing,” says Sheena Josselyn, a neuroscientist at the Hospital for Sick Children in Toronto. “It shows that your memories are really just activities of different cells, and they can take the place of an actual thing that happened by just activating some cells in the brain,” she says. “People have been playing around with this idea for a while, but having a theory and showing it are two different things.”

"Remarkably, the recall of this false memory recruited the same fear centers that natural fear memory recall recruits, such as the amygdala," said Xu Liu, a post-doctoral fellow and co-first author of the study. The recall of this false memory drove an active fear response in associated parts of the brain, making it indistinguishable from a real memory. "In a sense, to the animal, the false memory seems to have felt like a 'real' memory," he said.

These kinds of experiments show us just how reconstructive the process of memory actually is," said Steve Ramirez, a graduate student in the Tonegawa lab and the lead author of the paper. "Memory is not a carbon copy, but rather a reconstruction, of the world we've experienced. Our hope is that, by proposing a neural explanation for how false memories may be generated, down the line we can use this kind of knowledge to inform, say, a courtroom about just how unreliable things like eyewitness testimony can actually be."



SOURCE  RIKEN

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 Optogenetics  

A new tool that could help map and track the interactions between neurons in different areas of the brain is being developed by University of Texas Arlington assistant professor of physics Samarendra Mohanty. The technology would be useful in the BRAIN (Brain Research Through Advancing Innovative Neurotechnologies) mapping initiative.

Anew tool being developed by University of Texas Arlington assistant professor of physics could help scientists map and track the interactions between neurons inside different areas of the brain.

The journal Optics Letters recently published a paper by Samarendra Mohanty, a member of the Lifeboat Foundation Advisory Board, on the development of a fiber-optic, two-photon, optogenetic stimulator and its use on human cells in a laboratory.

The tiny tool builds on Mohanty’s previous discovery that near-infrared light can be used to stimulate a light-sensitive protein introduced into living cells and neurons in the brain. This new method could show how different parts of the brain react when a linked area is stimulated.

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The technology would be useful in the BRAIN activity mapping initiative recently championed by President Barack Obama, Mohanty said. BRAIN stands for Brain Research Through Advancing Innovative Neurotechnologies and will include $100 million in government investments in research.

“Scientists have spent a lot of time looking at the physical connections between different regions of the brain. But that information is not sufficient unless we examine how those connections function,” Mohanty said. “That’s where two-photon optogenetics comes into play. This is a tool not only to control the neuronal activity but to understand how the brain works.”

The two-photon optogenetic stimulation described in the paper involves introducing the gene for ChR2, a protein that responds to light, into a sample of excitable cells. A fiber-optic infrared beam of light can then be used to precisely excite the neurons in a tissue circuit.

In the brain, researchers would then observe responses in the excited area as well as other parts of the neural circuit. In living subjects, scientists would also observe the behavioral outcome, Mohanty said.

Optogenetic stimulation avoids damage to living tissue by using light to stimulate neurons instead of electric pulses used in past research. Mohanty’s method of using low-energy near-infrared light also enables more precision and a deeper focus than the blue or green light beams often used in optogenetic stimulation, the paper said.

Using fiber optics to deliver the two-photon optogenetic beam is another advance. Previous methods required bulky microscopes or complex scanning beams. Mohanty’s group is collaborating with UT Arlington Department of Psychology assistant professor Linda Perrotti to apply this technology in living animals.

“Dr. Mohanty’s innovations continue to be recognized because of the great potential they hold,” said Pamela Jansma, dean of the UT Arlington College of Science. “Hopefully, his work will one day provide researchers in other fields the tools they need to examine how the human body works and why normal processes sometimes fail.”



SOURCE  University of Texas Arlington

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