Posts tagged optogenetics
Articles and news from the latest research reports.
Holographic Technique Could Lead to Bionic Vision
Researchers led by biomedical engineering Professor Shy Shoham of the Technion-Israel Institute of Technology are testing the power of holography to artificially stimulate cells in the eye, with hopes of developing a new strategy for bionic vision restoration.
Computer-generated holography, they say, could be used in conjunction with a technique called optogenetics, which uses gene therapy to deliver light-sensitive proteins to damaged retinal nerve cells. In conditions such as Retinitis Pigmentosa (RP) - a condition affecting about one in 4000 people in the United States - these light-sensing cells degenerate and lead to blindness.
“The basic idea of optogenetics is to take a light-sensitive protein from another organism, typically from algae or bacteria, and insert it into a target cell, and that photosensitizes the cell,” Shoham explained.
Intense pulses of light can activate nerve cells newly sensitized by this gene therapy approach. But Shoham said researchers around the world are still searching for the best way to deliver the light patterns so that the retina “sees” or responds in a nearly normal way.
The plan is to someday develop a prosthetic headset or eyepiece that a person could wear to translate visual scenes into patterns of light that stimulate the genetically altered cells.
In their paper in the February 26 issue of Nature Communications, the Technion researchers show how light from computer-generated holography could be used to stimulate these repaired cells in mouse retinas. The key, they say, is to use a light stimulus that is intense, precise, and can trigger activity across a variety of cells all at once.
Light Switch Inside Brain: Laser Controls Individual Nerve Cells in Mouse
Activating and deactivating individual nerve cells in the brain is something many neuroscientists wish they could do, as it would help them to better understand how the brain works.
Scientists in Freiburg and Basel, Switzerland, have developed an implant that is able to genetically modify specific nerve cells, control them with light stimuli, and measure their electrical activity all at the same time. This novel 3-in-1 tool paves the way for completely new experiments in neurobiology, also at Freiburg’s new Cluster of Excellence BrainLinks-BrainTools.
Birthe Rubehn and her colleagues from the Department of Microsystems Engineering (IMTEK) and the Bernstein Center of the University of Freiburg as well as the Friedrich Miescher Institute for Biomedical Research in Basel describe the prototype of their implant in the journal Lab on a Chip. They report that initial experiments in which they implanted prototypes into mice were successful: The team was able to influence the activity of nerve cells in the brain in a controlled manner by means of laser light pulses.
The team used an innovative genetic technique that makes nerve cells change their activity by shining different colored lights on them. In optogenetics, genes from certain species of algae are inserted into the genome of another organism, for instance a mouse. The genes lead to the inclusion of light-sensitive pores for electrically charged particles into a nerve cell’s membrane. These additional openings allow neuroscientists to control the cells’ electrical activity.
However, only the new implant from Freiburg and Basel makes this principle actually practicable. The device, at its tip only a quarter of a millimeter wide and a tenth of a millimeter thick, was constructed on the basis of polymers, special plastics whose safety for implantation into the nervous system has been proven.
Unlike probes developed so far, it is capable of injecting substances necessary for genetic modification, emitting light for the stimulation of the nerve cells, and measuring the effect through various electrical contacts all at once. Besides optimizing the technique for production, the scientists want to develop a second version whose injection channel dissolves over time, reducing the implant’s size even further.
More than a century after it was first identified, Harvard scientists are shedding new light on a little-understood neural feedback mechanism that may play a key role in how the olfactory system works in the brain.
As described in a December 19 paper in Neuron by Venkatesh Murthy, Professor of Molecular and Cellular Biology, researchers have, for the first time, described how that feedback mechanism works by identifying where the signals go, and which type of neurons receive them. Three scientists from the Murthy lab were involved in the work: Foivos Markopoulos, Dan Rokni and David Gire.
"The image of the brain as a linear processor is a convenient one, but almost all brains, and certainly mammalian brains, do not rely on that kind of pure feed-forward system," Murthy explained. "On the contrary, it now appears that the higher regions of the brain which are responsible for interpreting olfactory information are communicating with lower parts of the brain on a near-constant basis."
Though researchers have known about the feedback system for decades, key questions about its precise workings, such as which neurons in the olfactory bulb receive the feedback signals, remained a mystery, partly because scientists simply didn’t have the technological tools needed to activate individual neurons and individual pathways.
"One of the challenges with this type of research is that these feedback neurons are not the only neurons that come back to the olfactory bulb," Murthy explained. "The challenge has always been that there’s no easy way to pick out just one type of neuron to activate."
To do it, Murthy and his team turned to a technique called optogenetics.
Using a virus that has been genetically-modified to produce a light-sensitive protein, Murthy and his team marked specific neurons, which become active when hit with laser light. Researchers were then able to trace the feedback mechanism from the brain’s processing centers back to the olfactory bulb.
Reaching that level of precision was critical, Murthy explained, because while olfactory bulb contains many “principal” neurons which are responsible for sending signals on to other parts of the brain, it is also packed with interneurons, which appear to play a role in formatting olfactory information as it comes into the brain.
(Image: BigStock)
Stress-Resilience/Susceptibility Traced to Neurons in Reward Circuit
A specific pattern of neuronal firing in a brain reward circuit instantly rendered mice vulnerable to depression-like behavior induced by acute severe stress, a study supported by the National Institutes of Health has found. When researchers used a high-tech method to mimic the pattern, previously resilient mice instantly succumbed to a depression-like syndrome of social withdrawal and reduced pleasure-seeking – they avoided other animals and lost their sweet tooth. When the firing pattern was inhibited in vulnerable mice, they instantly became resilient.
“For the first time, we have shown that split-second control of specific brain circuitry can switch depression-related behavior on and off with flashes of an LED light,” explained Ming-Hu Han, Ph.D., of the Mount Sinai School of Medicine, New York City, a grantee of NIH’s National Institute of Mental Health (NIMH). “These results add to mounting clues about the mechanism of fast-acting antidepressant responses.” Han, Eric Nestler, M.D., Ph.D., of Mount Sinai, and colleagues, report on their study online, Dec. 12, 2012, in the journal Nature.
In a companion article, NIMH grantees Kay Tye, Ph.D., of the Massachusetts Institute of Technology, Cambridge, Mass., and Karl Deisseroth, M.D., Ph.D., of Stanford University, Stanford, Calif., used the same cutting-edge technique to control mouse brain activity in real time. Their study reveals that the same reward circuit neuronal activity pattern had the opposite effect when the depression-like behavior was induced by daily presentations of chronic, unpredictable mild physical stressors, instead of by shorter-term exposure to severe social stress.
Prior to the new studies, Han’s team suspected that a telltale pattern – rapid firing of neurons that secrete the chemical messenger dopamine in a key circuit hub – makes an animal vulnerable to the depression-like effects of acute severe stress, and that slower firing supports resilience. But they lacked direct, real-time evidence.
To pinpoint cause-and-effect, they turned to a research technology pioneered by Deisseroth, called optogenetics. It melds fiber optics and genetic engineering to precisely control the activity of a specific brain circuit in a living, behaving animal. Genetically modified viruses are used to inject light-reactive proteins, borrowed from primitive organisms like algae, to make the circuitry similarly light-responsive.
Researchers at Stanford University have successfully induced and relieved depression-like deficiencies in both pleasure and motivation in mice by controlling just a single area of the brain known as the ventral tegmental area. It is the first time that well-defined types of neurons within a specific brain region have been directly tied to the control of myriad symptoms of major depressive illness.
In the paper published in Nature on Dec. 12, Stanford bioengineer Karl Deisseroth, MD, PhD, and a team including postdoctoral scholars Kay Tye, PhD, and Melissa Warden, PhD, and research assistant Julie Mirzabekov have used a technique known as optogenetics to pinpoint a specific brain location that produces multiple depression-like symptoms. The region in question is the ventral tegmental area, or VTA, a source of dopamine and a central player in the brain’s internal motivation and reward systems.
“We have for the first time directly tied dopamine neurons in the VTA to controlling and relieving these very different and diverse symptoms,” said Deisseroth, the study’s senior author and a professor of bioengineering and of psychiatry and behavioral sciences. “While depression is a complex disease with still many unknowns, this knowledge may help launch new kinds of investigation into the pathways of depression in the brain, and develop concepts to help people suffering from depression.”
Deisseroth’s team was able to both induce and relieve multiple depression-like symptoms in laboratory mice by genetically modifying the dopamine neurons in the VTA to be sensitive to light. Using fiber optic cables inserted in rodents’ brains, they could then instantaneously produce and inhibit the depression-like symptoms by turning the light on and off. This research technique, developed by Deisseroth at Stanford in 2005, is known as optogenetics.
(Image Credit: iStockphoto.com)
First measurements made of key brain links
Until now, brain scientists have been almost completely in the dark about how most of the nonspecific thalamus interacts with the prefrontal cortex, a relationship believed to be key in such fundamental functions as maintaining consciousness and mental arousal. Brown University researchers performed a set of experiments, described in the Journal of Neuroscience, to explore and measure those circuits for the first time.
A 3-D Light Switch for the Brain
A new tool for neuroscientists delivers a thousand pinpricks of light to a chunk of gray matter smaller than a sugar cube. The new fiber-optic device, created by biologists and engineers at the Massachusetts Institute of Technology (MIT) in Cambridge, is the first tool that can deliver precise points of light to a 3-D section of living brain tissue. The work is a step forward for a relatively new but promising technique that uses gene therapy to turn individual brain cells on and off with light.
Scientists can use the new 3-D “light switch” to better understand how the brain works. It might also be used one day to create neural prostheses that could treat conditions such as Parkinson’s disease and epilepsy. The researchers describe their device in a paper published today in the Optical Society’s (OSA) journal Optics Letters.
The technique of manipulating neurons with light is only a few years old, but the authors estimate that thousands of scientists are already using this technology, called optogenetics, to study the brain. In optogenetics, researchers first sensitize select cells in the brain to a particular color of light. Then, by illuminating precise areas of the brain, they are able to selectively activate or deactivate the individual neurons that have been sensitized.
Ed Boyden, a synthetic biologist at MIT and co-lead researcher on the paper, is a pioneer of this emerging field, which he says offers the ability to probe connections in the brain.
"You can see neural activity in the brain that is associated with specific behaviors," Boyden says, “but is it important? Or is it a passive copy of important activity located elsewhere in the brain? There’s no way to know for sure if you just watch.” Optogenetics allows scientists to play a more active role in probing the brain’s connections, to fire up one type of cell or deactivate another and then observe the effect on a behavior, such as quieting a seizure.
Unlike the previous, 1-D versions of this light-emitting device, the new tool delivers light to the brain in three dimensions, opening the potential to explore entire circuits within the brain. So far, the 3-D version has been tested in mice, although Boyden and colleagues have used earlier optogenetic technologies with non-human primates as well.
Flipping on the Lights to Halt Seizures
Targeted light transmission to genetically altered brain cells stops seizures cold.
Strobe lights can trigger epileptic seizures. Now imagine a light that stops a seizure a split second after it starts.
By applying pulses of light to genetically altered nerve cells deep in rat brains, researchers at Stanford and Pierre and Marie Curie University in France have done just that. Their results, which showed for the first time how a part of the brain called the thalamus is involved with epileptic seizures, were published in Nature Neuroscience.
The study could point toward new targets for epilepsy treatment, says Ed Boyden, associate professor and leader of the Synthetic Biology Group at MIT. Boyden was not involved in the work. Some ideas “might emerge immediately from knowing new targets to insert deep brain stimulation electrodes,” a type of device already used to help people with epilepsy, Boyden says.
The latest research looked at a kind of seizure that sometimes follows damage to the cerebral cortex, the outer part of the brain, from strokes or head injuries. Previous reports had hinted that the cortex might also communicate during a seizure with the thalamus, the brain’s message relay center.
In the current study, experiments with rats confirmed that the thalamus propagates seizure activity originating in the cortex. To see if the thalamus could be a target for treating seizures, Jeanne Paz, the paper’s lead author, and her colleagues turned to optogenetics, a technology that lets researchers use light to turn brain cells on and off.
For the “genetics” part, they used a virus to insert the DNA code for a light-sensitive protein into thalamus cells of rats. When exposed to light, the protein interferes with these cells’ ability to communicate.
The researchers then developed a light source that would turn on only when a rat had a seizure. To detect seizures, they implanted electrodes into the rats’ brains. When these electrodes registered a seizure starting, light from a laser was aimed directly at the genetically altered thalamus cells. The result, the researchers found, was that flipping on the light immediately stopped the seizure activity, proving that the thalamus is needed to keep seizures going.
“We’re excited that just a brief light exposure was enough to stop the seizure,” says John Huguenard, Stanford professor of neurology and neurological sciences and an author of the study.
However, Huguenard says, an optogenetics-based brain implant to control seizures is a long way off because of the unknown risks of altering a person’s DNA with a virus. “I would want to be cautious,” he says.
(Source: technologyreview.com)
How the brain controls our habits
Habits are behaviors wired so deeply in our brains that we perform them automatically. This allows you to follow the same route to work every day without thinking about it, liberating your brain to ponder other things, such as what to make for dinner.
However, the brain’s executive command center does not completely relinquish control of habitual behavior. A new study from MIT neuroscientists has found that a small region of the brain’s prefrontal cortex, where most thought and planning occurs, is responsible for moment-by-moment control of which habits are switched on at a given time.
“We’ve always thought — and I still do — that the value of a habit is you don’t have to think about it. It frees up your brain to do other things,” says Institute Professor Ann Graybiel, a member of the McGovern Institute for Brain Research at MIT. “However, it doesn’t free up all of it. There’s some piece of your cortex that’s still devoted to that control.”
The new study offers hope for those trying to kick bad habits, says Graybiel, senior author of the new study, which appears this week in the Proceedings of the National Academy of Sciences. It shows that though habits may be deeply ingrained, the brain’s planning centers can shut them off. It also raises the possibility of intervening in that brain region to treat people who suffer from disorders involving overly habitual behavior, such as obsessive-compulsive disorder.
Discovery of gatekeeper nerve cells explains the effect of nicotine on learning and memory
Researchers at Uppsala University have, together with Brazilian collaborators, discovered a new group of nerve cells that regulate processes of learning and memory. These cells act as gatekeepers and carry a receptor for nicotine, which can explain our ability to remember and sort information.
The discovery of the gatekeeper cells, which are part of a memory network together with several other nerve cells in the hippocampus, reveal new fundamental knowledge about learning and memory. The study is published today in Nature Neuroscience.
The hippocampus is an area of the brain that is important for consolidation of information into memories and helps us to learn new things. The newly discovered gatekeeper nerve cells, also called OLM-alpha2 cells, provide an explanation to how the flow of information is controlled in the hippocampus.
“It is known that nicotine improves cognitive processes including learning and memory, but this is the first time that an identified nerve cell population is linked to the effects of nicotine”, says Professor Klas Kullander at Uppsala University.