from the there's-a-light dept.
Researchers have created a protein that breaks into two pieces when exposed to light:
Researchers at the University of Alberta have developed a new method of controlling biology at the cellular level using light. The tool -- called a photocleavable protein -- breaks into two pieces when exposed to light, allowing scientists to study and manipulate activity inside cells in new and different ways.
First, scientists use the photocleavable protein to link cellular proteins to inhibitors, preventing the cellular proteins from performing their usual function. This process is known as caging. "By shining light into the cell, we can cause the photocleavable protein to break, removing the inhibitor and uncaging the protein within the cell," said lead author Robert Campbell, professor in the Department of Chemistry. Once the protein is uncaged, it can start to perform its normal function inside the cell. The tool is relatively easy to use and widely applicable for other research that involves controlling processes inside a cell.
Optogenetic control with a photocleavable protein, PhoCl (DOI: 10.1038/nmeth.4222) (DX)
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Optogenetics is a marvel of our age, enabling neuroscientists to turn brain cells on and off with pulses of light. But until now there's been an obvious difficulty: How do you deliver that light to brain cells that are tucked inside an animal's skull?
Today we get the best answer yet, from the Stanford lab of Ada Poon. She and her colleagues have invented a tiny, wireless LED device that can be fully implanted beneath the skin of a mouse. The device lets researchers turn on the light and stimulate neurons when the mouse is scampering around, behaving more or less normally. This system, described today in the journal Nature Methods, seems a big improvement over previous technology, which used wires or bulky head-mounted devices to activate the light switch.
Here's a quick optogenetics primer, in case you need it. The technique makes use of neurons that have been genetically altered to respond to light, often with the introduction of genes from a strain of green algae. Researchers can control which part of a mouse brain contains these light-sensitive neurons, and they can then study the function of that brain region by activating the neurons—essentially turning them on and off—while watching the animal's behavior. Using this method, scientists can learn about basic brain anatomy or study dysfunctions seen in human diseases.
An upcoming human trial will attempt to use optogenetics to treat conditions such as retinitis pigmentosa:
In the next month, scientists from RetroSense Therapeutics will inject a virus deep into the retina of legally blind human volunteers. The virus will carry what is perhaps the most monumental payload in modern neuroscience history: DNA that codes for channelrhodopsin-2, a light-responsive protein isolated from algae that — under blue light — activates cells in the retina, thereby transmitting visual information to the brain.
Forget electronic implants. If all goes well, these volunteers will be able to see again using their own eyes — but in no way a human being has ever experienced sight before. Whoa.
But the stakes are even higher: if this works, it means that optogenetics — a revolutionary neuroscience technique using channelrhodopsin-2 and other light-activated proteins — is feasible in humans as therapy. Considering optogenetics has been used in mice to implant false memories, treat cocaine addiction, attenuate OCD symptoms, trigger sexual advances and aggression and reverse motor deficits in Parkinson's disease — just to name a few feats— the technique could completely transform the face of neurology. "This is going to be a gold mine of information about doing optogenetics studies in humans," said Dr. Antonello Bonci, the scientific director of the intramural research program at the National Institute on Drug Abuse, to MIT Technology Review.
[...] If it works, what will the patients see? No one can say for sure. After all, this will be the first time humans experience the visual world through the light sensor of algae. But studies with blind lab mice may give us a hint. In one previous study, after optogenetics treatment, previously blind mice could swim out of a chamber in which the escape route was brightly lit. On average, they escaped as fast as mice with normal vision.
Optogenetics has been used to activate neurons in mice with Alzheimer's-like symptoms, allowing them to remember the fear caused by an electric shock:
Memories banished by Alzheimer's can in theory be rescued by stimulating nerve cells to grow new connections, a study has shown. The research, conducted in mice, raises the possibility of future treatments that reverse memory loss in early stages of the disease. Scientists used a technique called optogenetics, which uses light to activate cells tagged with a special photo-sensitive protein. It was tested on mice with Alzheimer's-like symptoms that quickly forgot the experience of receiving a mild electric shock to their feet. After tagged cells in their brains were stimulated with light, their memory returned and they displayed a fear response when placed in the chamber where the shock had been applied an hour earlier.
The optogenetic treatment helped the neurons re-grow small buds called dendritic spines, which form synaptic connections with other cells. Although the same technique cannot be used in humans, the research points the way to future memory-retrieving therapies, say the researchers. Lead scientist Prof Susumu Tonegawa, from the Picower institute for learning and memory at the Massachusetts Institute of Technology (MIT) in the US, said: "The important point is, this a proof of concept. That is, even if a memory seems to be gone, it is still there. It's a matter of how to retrieve it."
The research, published in the journal Nature, specifically targeted memory cells in the hippocampus region of the brain previously identified by Tonegawa's team. Two different strains of mice, genetically engineered to develop Alzheimer's symptoms, plus a control group of healthy animals, were used in the experiment.
Memory retrieval by activating engram cells in mouse models of early Alzheimer's disease (DOI: 10.1038/nature17172)
Imagine if we could enhance good memories for those suffering from dementia and wipe away bad memories for people with post-traumatic stress disorder.
Researchers have taken a step toward the possibility of tuning the strength of memory by manipulating one of the brain's natural mechanisms for signaling involved in memory, a neurotransmitter called acetylcholine.
Brain mechanisms underlying memory are not well understood, but most scientists believe that the region of the brain most involved in emotional memory is the amygdala. Acetylcholine is delivered to the amygdala by cholinergic neurons that reside in the base of the brain.
[...] For a new study published in the journal Neuron , researchers used a fear-based memory model in mice to test the underlying mechanism of memory because fear is a strong and emotionally charged experience. They used optogenetics, a newer research method using light to control cells in living tissue, to stimulate specific populations of cholinergic neurons during the experiments.
Two findings stand out. First, when they increased acetylcholine release in the amygdala during the formation of a traumatic memory, it greatly strengthened memory—making the memory last more than twice as long as normal. Then, when they decreased acetylcholine signaling in the amygdala during a traumatic experience, one that normally produces a fear response, they could actually wipe the memory out.
"This second finding was particularly surprising, as we essentially created fearless mice by manipulating acetylcholine circuits in the brain," Role says.
Sounds reminiscent of how they erased memories in the Philip K Dick film adaptation, Paycheck.
[Acetylcholine has been implicated in addiction to alcohol and nicotine; see, for example, Alcohol and nicotinic acetylcholine receptors (abstract) and full article (pdf) -Ed.]
An optogenetics technique has been used to activate mouse neurons associated with predatory behavior:
With a flash of light, researchers have induced mice to pounce on anything in their line of sight. Researchers from Yale University and the University of São Paulo isolated the regions of the mouse brain that control both hunting and biting, and say they can activate the neurons involved on command. The research should help illuminate another small part of the neural pathways that connect the outside world to our internal computations.
In this case, the researchers were interested in the link between an outside stimulus — like seeing a delicious cricket — and an action, such as pouncing on said cricket. Their research [open, DOI: 10.1016/j.cell.2016.12.027] [DX], published Thursday in Cell, looks at the second part of that question. The researchers used a technique called optogenetics to empirically test the findings of a previous paper that described mouse brain regions involved in predatory behavior. They implanted genetic material from light-sensitive algae into neurons that control hunting and biting, and used flashes of laser light to stimulate them.
The results were convincing: When target regions were activated, the mice pounced without a second thought, following their predatory instincts. When the laser turned off, the mice returned to normal behavior. And the mice didn't limit their attacks to prey: When the kill switch was activated, they attacked sticks and bottle caps as well.