neurosciencestuff:

Tool helps guide brain cancer surgery

A tool to help brain surgeons test and more precisely remove cancerous tissue was successfully used during surgery, according to a Purdue University and Brigham and Women’s Hospital study.

The Purdue-designed tool sprays a microscopic stream of charged solvent onto the tissue surface to gather information about its molecular makeup and produces a color-coded image that reveals the location, nature and concentration of tumor cells.

 ”In a matter of seconds this technique offers molecular information that can detect residual tumor that otherwise may have been left behind in the patient,” said R. Graham Cooks, the Purdue professor who co-led the research team. “The instrumentation is relatively small and inexpensive and could easily be installed in operating rooms to aid neurosurgeons. This study shows the tremendous potential it has to enhance patient care.”

Current surgical methods rely on the surgeon’s trained eye with the help of an operating microscope and imaging from scans performed before surgery, Cooks said.

"Brain tumor tissue looks very similar to healthy brain tissue, and it is very difficult to determine where the tumor ends and the normal tissue begins," he said. "In the brain, millimeters of tissue can mean the difference between normal and impaired function. Molecular information beyond what a surgeon can see can help them precisely and comprehensively remove the cancer."

The mass spectrometry-based tool had previously been shown to accurately identify the cancer type, grade and tumor margins of specimens removed during surgery based on an evaluation of the distribution and amounts of fatty substances called lipids within the tissue. This study took the analysis a step further by additionally evaluating a molecule associated with cell growth and differentiation that is considered a biomarker for certain types of brain cancer, he said.

"We were able to identify a single metabolite biomarker that provides information about tumor classification, genotype and the prognosis for the patient," said Cooks, the Henry Bohn Hass Distinguished Professor of Chemistry. "Through mass spectrometry all of this information can be obtained from a biopsy in a matter of minutes and without significantly interrupting the surgical procedure."

For this study, which included validation on samples and use during two patients’ surgical procedures, the tool was tuned to identify the lipid metabolite 2-hydroxyglutarate or 2-HG. This biomarker is associated with more than 70 percent of gliomas and can be used to classify the tumors, he said.  

A paper detailing the results of the National Institutes of Health-funded study will be published in an upcoming issue of the Proceedings of the National Academy of Sciences and is published online.

In mass spectrometry molecules are electrically charged and turned into ions so that they can be identified by their mass. The new tool relies an ambient mass spectrometry analysis technique developed by Cooks and his colleagues called desorption electrospray ionization, or DESI, which eliminated the need for chemical manipulations of samples and containment in a vacuum chamber for ionization. DESI allows ionization to occur directly on surfaces outside of the mass spectrometers, making the process much simpler, faster and more applicable to surgical settings.

The tool couples a DESI mass spectrometer with a software program designed by the research team that uses the results to characterize the brain tumors and detect boundaries between healthy and cancerous tissue.  The program is based on earlier studies of lipid patterns that correspond to different types and grades of cancer and currently covers the two most common types of brain tumors, gliomas and meningiomas. These two types of tumors combined account for about 65 percent of all brain tumors and 80 percent of all malignant brain tumors, according to the American Brain Tumor Association.

Additional classification methodologies and metabolite biomarkers could be added to tailor the tool to different types of cancer, Cooks said.

The brain surgery was performed in the Advanced Multi-Modality Image Guided Operating suite, or AMIGO at Brigham and Women’s Hospital.

Dr. Nathalie Agar, director of the Surgical Molecular Imaging Laboratory within the neurosurgery department at Brigham and Women’s Hospital, led the study.

neurosciencestuff:

Do not disturb! How the brain filters out distractions
You know the feeling? You are trying to dial a phone number from memory… you have to concentrate…. then someone starts shouting out other numbers nearby. In a situation like that, your brain must ignore the distraction as best it can so as not to lose vital information from its working memory. A new paper published in Neuron by a team of neurobiologists led by Professor Andreas Nieder at the University of Tübingen gives insight into just how the brain manages this problem.
The researchers put rhesus monkey in a similar situation. The monkeys had to remember the number of dots in an image and reproduce the knowledge a moment later. While they were taking in the information, a distraction was introduced, showing a different number of dots. And even though the monkeys were mostly able to ignore the distraction, their concentration was disturbed and their memory performance suffered.
Measurements of the electrical activity of nerve cells in two key areas of the brain showed a surprising result: nerve cells in the prefrontal cortex signaled the distraction while it was being presented, but immediately restored the remembered information (the number of dots) once the distraction was switched off. In contrast, nerve cells in the parietal cortex were unimpressed by the distraction and reliably transmitted the information about the correct number of dots.
These findings provide important clues about the strategies and division of labor among different parts of the brain when it comes to using the working memory. “Different parts of the brain appear to use different strategies to filter out distractions,” says Dr. Simon Jacob, who carried out research in Tübingen before switching to the Psychiatric Clinic at the Charité hospitals in Berlin. “Nerve cells in the parietal cortex simply suppress the distraction, while nerve cells in the prefrontal cortex allow themselves to be momentarily distracted – only to return immediately to the truly important memory content.”
The researchers were surprised by the two brain areas’ difference in sensitivity to distraction. “We had assumed that the prefrontal cortex is able to filter out all kinds of distractions, while the parietal cortex was considered more vulnerable to disturbances,” says Professor Nieder. “We will have to rethink that. The memory-storage tasks and the strategies of each brain area are distributed differently from what we expected.”

neurosciencestuff:

Do not disturb! How the brain filters out distractions

You know the feeling? You are trying to dial a phone number from memory… you have to concentrate…. then someone starts shouting out other numbers nearby. In a situation like that, your brain must ignore the distraction as best it can so as not to lose vital information from its working memory. A new paper published in Neuron by a team of neurobiologists led by Professor Andreas Nieder at the University of Tübingen gives insight into just how the brain manages this problem.

The researchers put rhesus monkey in a similar situation. The monkeys had to remember the number of dots in an image and reproduce the knowledge a moment later. While they were taking in the information, a distraction was introduced, showing a different number of dots. And even though the monkeys were mostly able to ignore the distraction, their concentration was disturbed and their memory performance suffered.

Measurements of the electrical activity of nerve cells in two key areas of the brain showed a surprising result: nerve cells in the prefrontal cortex signaled the distraction while it was being presented, but immediately restored the remembered information (the number of dots) once the distraction was switched off. In contrast, nerve cells in the parietal cortex were unimpressed by the distraction and reliably transmitted the information about the correct number of dots.

These findings provide important clues about the strategies and division of labor among different parts of the brain when it comes to using the working memory. “Different parts of the brain appear to use different strategies to filter out distractions,” says Dr. Simon Jacob, who carried out research in Tübingen before switching to the Psychiatric Clinic at the Charité hospitals in Berlin. “Nerve cells in the parietal cortex simply suppress the distraction, while nerve cells in the prefrontal cortex allow themselves to be momentarily distracted – only to return immediately to the truly important memory content.”

The researchers were surprised by the two brain areas’ difference in sensitivity to distraction. “We had assumed that the prefrontal cortex is able to filter out all kinds of distractions, while the parietal cortex was considered more vulnerable to disturbances,” says Professor Nieder. “We will have to rethink that. The memory-storage tasks and the strategies of each brain area are distributed differently from what we expected.”

landscapelifescape:

Montblanc mountains, France

 by alexandre-deschaumes

theeconomist:

Daily chart: Everything you need to know about UFOs
On July 2nd avid watchers of the skies celebrate World UFO day.The National UFO Reporting Centre, a non-profit, has catalogued almost 90,000 reported sightings of UFOs, mostly in America, since 1974. It turns out that aliens are considerate: they seldom disturb earthlings during working or sleeping hours. Rather, they tend to arrive in the evening, especially on Fridays, when folks are sitting on the front porch nursing their fourth beer.

theeconomist:

Daily chart: Everything you need to know about UFOs

On July 2nd avid watchers of the skies celebrate World UFO day.The National UFO Reporting Centre, a non-profit, has catalogued almost 90,000 reported sightings of UFOs, mostly in America, since 1974. It turns out that aliens are considerate: they seldom disturb earthlings during working or sleeping hours. Rather, they tend to arrive in the evening, especially on Fridays, when folks are sitting on the front porch nursing their fourth beer.

neurosciencestuff:

Study shows puzzle games can improve mental flexibility
A recent study by Nanyang Technological University (NTU) scientists showed that adults who played the physics-based puzzle video game Cut the Rope regularly, for as little as an hour a day, had improved executive functions.
The executive functions in your brain are important for making decisions in everyday life when you have to deal with sudden changes in your environment – better known as thinking on your feet. An example would be when the traffic light turns amber and a driver has to decide in an instant if he will be able to brake in time or if it is safer to travel across the junction/intersection.
The video game study by Assistant Professor Michael D. Patterson and his PhD student Mr Adam Oei, tested four different games for the mobile platform, as their previous research had shown that different games trained different skills.
The games varied in their genres, which included a first person shooter (Modern Combat); arcade (Fruit Ninja); real-time strategy (StarFront Collision); and a complex puzzle (Cut the Rope).
NTU undergraduates, who were non-gamers, were then selected to play an hour a day, 5 days a week on their iPhone or iPod Touch. This video game training lasted for 4 weeks, a total of 20 hours.
Prof Patterson said students who played Cut the Rope, showed significant improvement on executive function tasks while no significant improvements were observed in those playing the other three games.
“This finding is important because previously, no video games have demonstrated this type of broad improvement to executive functions, which are important for general intelligence, dealing with new situations and managing multitasking,” said Prof Patterson, an expert in the psychology of video games.
“This indicates that while some games may help to improve mental abilities, not all games give you the same effect. To improve the specific ability you are looking for, you need to play the right game,” added Mr Oei.
The abilities tested in this study included how fast the players can switch tasks (an indicator of mental flexibility); how fast can the players adapt to a new situation instead of relying on the same strategy (the ability to inhibit prepotent or predominant responses); and how well they can focus on information while blocking out distractors or inappropriate responses (also known as the Flanker task in cognitive psychology).
Prof Patterson said the reason Cut the Rope improved executive function in their players was probably due to the game’s unique puzzle design. Strategies which worked for earlier levels would not work in later levels, and regularly forced the players to think creatively and try alternate solutions. This is unlike most other video games which keep the same general mechanics and goals, and just speed up or increase the number of items to keep track of. 
After 20 hours of game play, players of Cut the Rope could switch between tasks 33 per cent faster, were 30 per cent faster in adapting to new situations, and 60 per cent better in blocking out distractions and focusing on the tasks at hand than before training.
All three tests were done one week after the 52 students had finished playing their assigned game, to ensure that these were not temporary gains due to motivation or arousal effects.
The study will be published in the academic journal, Computers in Human Behavior, this August, but is available currently online. This is the first study that showed broad transfer to several different executive functions, further providing evidence the video games can be effective in training human cognition.
“This result could have implications in many areas such as educational, occupational and rehabilitative settings,” Prof Patterson said.
“In future, with more studies, we will be able to know what type of games improves specific abilities, and prescribe games that will benefit people aside from just being entertainment.”
In their previous study published last year in PloS One, a top academic journal, Prof Patterson and Mr Oei studied the effects mobile gaming had on 75 NTU undergraduates.
The non-gamers were instructed to play one of the following games: “match three” game Bejeweled, virtual life simulation game The Sims, and action shooter Modern Combat.
The study findings showed that adults who play action games improved their ability to track multiple objects in a short span of time, useful when driving during a busy rush hour; while other games improved the participants’ ability for visual search tasks, useful when picking out an item from a large supermarket.
Moving forward, the Prof Patterson is keen to look at whether there is any improvement from playing such games in experienced adult gamers and how much improvement one can make through playing games.

neurosciencestuff:

Study shows puzzle games can improve mental flexibility

A recent study by Nanyang Technological University (NTU) scientists showed that adults who played the physics-based puzzle video game Cut the Rope regularly, for as little as an hour a day, had improved executive functions.

The executive functions in your brain are important for making decisions in everyday life when you have to deal with sudden changes in your environment – better known as thinking on your feet. An example would be when the traffic light turns amber and a driver has to decide in an instant if he will be able to brake in time or if it is safer to travel across the junction/intersection.

The video game study by Assistant Professor Michael D. Patterson and his PhD student Mr Adam Oei, tested four different games for the mobile platform, as their previous research had shown that different games trained different skills.

The games varied in their genres, which included a first person shooter (Modern Combat); arcade (Fruit Ninja); real-time strategy (StarFront Collision); and a complex puzzle (Cut the Rope).

NTU undergraduates, who were non-gamers, were then selected to play an hour a day, 5 days a week on their iPhone or iPod Touch. This video game training lasted for 4 weeks, a total of 20 hours.

Prof Patterson said students who played Cut the Rope, showed significant improvement on executive function tasks while no significant improvements were observed in those playing the other three games.

“This finding is important because previously, no video games have demonstrated this type of broad improvement to executive functions, which are important for general intelligence, dealing with new situations and managing multitasking,” said Prof Patterson, an expert in the psychology of video games.

“This indicates that while some games may help to improve mental abilities, not all games give you the same effect. To improve the specific ability you are looking for, you need to play the right game,” added Mr Oei.

The abilities tested in this study included how fast the players can switch tasks (an indicator of mental flexibility); how fast can the players adapt to a new situation instead of relying on the same strategy (the ability to inhibit prepotent or predominant responses); and how well they can focus on information while blocking out distractors or inappropriate responses (also known as the Flanker task in cognitive psychology).

Prof Patterson said the reason Cut the Rope improved executive function in their players was probably due to the game’s unique puzzle design. Strategies which worked for earlier levels would not work in later levels, and regularly forced the players to think creatively and try alternate solutions. This is unlike most other video games which keep the same general mechanics and goals, and just speed up or increase the number of items to keep track of. 

After 20 hours of game play, players of Cut the Rope could switch between tasks 33 per cent faster, were 30 per cent faster in adapting to new situations, and 60 per cent better in blocking out distractions and focusing on the tasks at hand than before training.

All three tests were done one week after the 52 students had finished playing their assigned game, to ensure that these were not temporary gains due to motivation or arousal effects.

The study will be published in the academic journal, Computers in Human Behavior, this August, but is available currently online. This is the first study that showed broad transfer to several different executive functions, further providing evidence the video games can be effective in training human cognition.

“This result could have implications in many areas such as educational, occupational and rehabilitative settings,” Prof Patterson said.

“In future, with more studies, we will be able to know what type of games improves specific abilities, and prescribe games that will benefit people aside from just being entertainment.”

In their previous study published last year in PloS One, a top academic journal, Prof Patterson and Mr Oei studied the effects mobile gaming had on 75 NTU undergraduates.

The non-gamers were instructed to play one of the following games: “match three” game Bejeweled, virtual life simulation game The Sims, and action shooter Modern Combat.

The study findings showed that adults who play action games improved their ability to track multiple objects in a short span of time, useful when driving during a busy rush hour; while other games improved the participants’ ability for visual search tasks, useful when picking out an item from a large supermarket.

Moving forward, the Prof Patterson is keen to look at whether there is any improvement from playing such games in experienced adult gamers and how much improvement one can make through playing games.

thisistheverge:

'Transformers: Age of Extinction' review)
There’s an often-made argument that audiences should just shut their brains off and enjoy a mindless summer movie, but amazing visuals and action sequences can coexist with compelling characters and epic storylines. It’s why The Avengers was such a beloved successes, and why we’re all hoping J.J. Abrams can tap into some of that old-school Star Wars magic. Christopher Nolan’s career alone is proof that there is a want and a need for films that are both smart and broadly commercial. But as long as audiences continue to flock to movies like Transformers: Age of Extinction and forgive their shortcomings, that’s what Hollywood will make. Not the movies we want, but the movies we deserve.

thisistheverge:

'Transformers: Age of Extinction' review)
There’s an often-made argument that audiences should just shut their brains off and enjoy a mindless summer movie, but amazing visuals and action sequences can coexist with compelling characters and epic storylines. It’s why The Avengers was such a beloved successes, and why we’re all hoping J.J. Abrams can tap into some of that old-school Star Wars magic. Christopher Nolan’s career alone is proof that there is a want and a need for films that are both smart and broadly commercial. But as long as audiences continue to flock to movies like Transformers: Age of Extinction and forgive their shortcomings, that’s what Hollywood will make. Not the movies we want, but the movies we deserve.

thisistheverge:

Apple stopping development of Aperture and iPhoto for OS X
Back at WWDC, Apple showed off a preview of a new Photos app for OS X — and now it seems that new app will replace Apple’s longstanding iPhoto and Aperture software for photo editing on the desktop. According to The Loop, Apple will replace both iPhoto and its professional-grade Aperture software with the new Photos App when it launches. This isn’t a huge surprise, as Aperture hasn’t seen any major updates in quite some time and is beginning to feel somewhat out-of-date, but it’s still unexpected to see the company complete cede the professional photo software space to competitors like Adobe’s Lightroom.

thisistheverge:

Apple stopping development of Aperture and iPhoto for OS X
Back at WWDC, Apple showed off a preview of a new Photos app for OS X — and now it seems that new app will replace Apple’s longstanding iPhoto and Aperture software for photo editing on the desktop. According to The Loop, Apple will replace both iPhoto and its professional-grade Aperture software with the new Photos App when it launches. This isn’t a huge surprise, as Aperture hasn’t seen any major updates in quite some time and is beginning to feel somewhat out-of-date, but it’s still unexpected to see the company complete cede the professional photo software space to competitors like Adobe’s Lightroom.

thisistheverge:

Material world: how Google discovered what software is made of
The next era of Google design is about software as substance

thisistheverge:

Material world: how Google discovered what software is made of
The next era of Google design is about software as substance

neurosciencestuff:

To Advance Care for Patients with Brain Metastases: Reject Five Myths
A blue-ribbon team of national experts on brain cancer says that professional pessimism and out-of-date “myths,” rather than current science, are guiding — and compromising — the care of patients with cancers that spread to the brain.
In a special article published in the July issue of Neurosurgery, the team, led by an NYU Langone Medical Center neurosurgeon, argues that many past, key clinical trials were designed with out-of-date assumptions and the tendency of some physicians to “lump together” brain metastases of diverse kinds of cancer, often results in less than optimal care for individual patients. Furthermore, payers question the best care when it deviates from these misconceptions, the authors conclude.
“It’s time to abandon this unjustifiable nihilism and think carefully about more individualized care,” says lead author of the article, Douglas S. Kondziolka, M.D., MSc, FRCSC, Vice Chair of Clinical Research and Director of the Gamma Knife Program in the Department of Neurosurgery at NYU Langone.
The authors — who also say medical insurers help perpetuate the myths by denying coverage that deviates from them — identify five leading misconceptions that often lead to poorer care:
All tumor cell types act the same way once they spread to the brain. This oversimplification means that doctors assume that histologically diverse cancers respond the same way to chemotherapy and are equally sensitive (or insensitive) to radiation. It also means that patients are all assumed to be at the same risk of subsequent brain cancer relapses, and development of additional metastatic lesions; and that survival rates are similar as well. The authors point out that this type of thinking overlooks important biological differences in brain metastases resulting from different types of cancer, such as those originating in the lung, breast or skin.
The number of brain metastases is the best indicator for guiding management of the disease. Such strict adherence to quantity, the authors say, can wrongly limit treatment options. Physicians should look at total tumor burden, including the size and scope of metastases, rather than just how many metastases occur.
All cancers detectable in the brain already reflect the presence of micrometastases, or  smaller, newly formed tumors too miniscule to detect. Evidence, the authors say, suggests otherwise, and aggressively monitoring for, and treating, individual brain metastases can, in fact, improve tumor control and patient survival.
Whole brain radiation (WBR) is generally unjustified because it will cause disabling cognitive dysfunction if a patient lives long enough. Dr. Kondziolka and his co-authors say the risks and benefits of WBR should be evaluated for each patient, and that new studies examining the cognitive impact of WBR on thinking and learning are underway.
Most brain metastases cause obvious symptoms, making regular screening for them unnecessary, and unlikely to affect survival. The authors counter that advances in screening allow metastases to be detected earlier, and treated sooner, before symptoms occur.
“We are in an era of personalized medicine,” Dr. Kondziolka says, “and we need to begin thinking that way.” The authors further write: “It is time for fresh thinking and new critical analyses,” urging consideration of updated clinical trial designs that include comparison of matched cohorts and cost effectiveness factors. In addition to research that pays more attention to specific cell types and overall tumor burden, investigators should focus on tools available from advances in molecular biology and genetic subtyping and on efforts to learn “why some patients with a given primary cancer develop brain tumors and others do not.”
Ultimately, the authors hope better stratifying patients will improve care for patients with diverse brain metastases.

neurosciencestuff:

To Advance Care for Patients with Brain Metastases: Reject Five Myths

A blue-ribbon team of national experts on brain cancer says that professional pessimism and out-of-date “myths,” rather than current science, are guiding — and compromising — the care of patients with cancers that spread to the brain.

In a special article published in the July issue of Neurosurgery, the team, led by an NYU Langone Medical Center neurosurgeon, argues that many past, key clinical trials were designed with out-of-date assumptions and the tendency of some physicians to “lump together” brain metastases of diverse kinds of cancer, often results in less than optimal care for individual patients. Furthermore, payers question the best care when it deviates from these misconceptions, the authors conclude.

“It’s time to abandon this unjustifiable nihilism and think carefully about more individualized care,” says lead author of the article, Douglas S. Kondziolka, M.D., MSc, FRCSC, Vice Chair of Clinical Research and Director of the Gamma Knife Program in the Department of Neurosurgery at NYU Langone.

The authors — who also say medical insurers help perpetuate the myths by denying coverage that deviates from them — identify five leading misconceptions that often lead to poorer care:

  1. All tumor cell types act the same way once they spread to the brain. This oversimplification means that doctors assume that histologically diverse cancers respond the same way to chemotherapy and are equally sensitive (or insensitive) to radiation. It also means that patients are all assumed to be at the same risk of subsequent brain cancer relapses, and development of additional metastatic lesions; and that survival rates are similar as well. The authors point out that this type of thinking overlooks important biological differences in brain metastases resulting from different types of cancer, such as those originating in the lung, breast or skin.
  2. The number of brain metastases is the best indicator for guiding management of the disease. Such strict adherence to quantity, the authors say, can wrongly limit treatment options. Physicians should look at total tumor burden, including the size and scope of metastases, rather than just how many metastases occur.
  3. All cancers detectable in the brain already reflect the presence of micrometastases, or  smaller, newly formed tumors too miniscule to detect. Evidence, the authors say, suggests otherwise, and aggressively monitoring for, and treating, individual brain metastases can, in fact, improve tumor control and patient survival.
  4. Whole brain radiation (WBR) is generally unjustified because it will cause disabling cognitive dysfunction if a patient lives long enough. Dr. Kondziolka and his co-authors say the risks and benefits of WBR should be evaluated for each patient, and that new studies examining the cognitive impact of WBR on thinking and learning are underway.
  5. Most brain metastases cause obvious symptoms, making regular screening for them unnecessary, and unlikely to affect survival. The authors counter that advances in screening allow metastases to be detected earlier, and treated sooner, before symptoms occur.

“We are in an era of personalized medicine,” Dr. Kondziolka says, “and we need to begin thinking that way.” The authors further write: “It is time for fresh thinking and new critical analyses,” urging consideration of updated clinical trial designs that include comparison of matched cohorts and cost effectiveness factors. In addition to research that pays more attention to specific cell types and overall tumor burden, investigators should focus on tools available from advances in molecular biology and genetic subtyping and on efforts to learn “why some patients with a given primary cancer develop brain tumors and others do not.”

Ultimately, the authors hope better stratifying patients will improve care for patients with diverse brain metastases.

neurosciencestuff:

Controlling movement with light
For the first time, MIT neuroscientists have shown they can control muscle movement by applying optogenetics — a technique that allows scientists to control neurons’ electrical impulses with light — to the spinal cords of animals that are awake and alert.  
Led by MIT Institute Professor Emilio Bizzi, the researchers studied mice in which a light-sensitive protein that promotes neural activity was inserted into a subset of spinal neurons. When the researchers shone blue light on the animals’ spinal cords, their hind legs were completely but reversibly immobilized. The findings, described in the June 25 issue of PLoS One, offer a new approach to studying the complex spinal circuits that coordinate movement and sensory processing, the researchers say.
In this study, Bizzi and Vittorio Caggiano, a postdoc at MIT’s McGovern Institute for Brain Research, used optogenetics to explore the function of inhibitory interneurons, which form circuits with many other neurons in the spinal cord. These circuits execute commands from the brain, with additional input from sensory information from the limbs.
Previously, neuroscientists have used electrical stimulation or pharmacological intervention to control neurons’ activity and try to tease out their function. Those approaches have revealed a great deal of information about spinal control, but they do not offer precise enough control to study specific subsets of neurons.
Optogenetics, on the other hand, allows scientists to control specific types of neurons by genetically programming them to express light-sensitive proteins. These proteins, called opsins, act as ion channels or pumps that regulate neurons’ electrical activity. Some opsins suppress activity when light shines on them, while others stimulate it.
“With optogenetics, you are attacking a system of cells that have certain characteristics similar to each other. It’s a big shift in terms of our ability to understand how the system works,” says Bizzi, who is a member of MIT’s McGovern Institute.
Muscle control
Inhibitory neurons in the spinal cord suppress muscle contractions, which is critical for maintaining balance and for coordinating movement. For example, when you raise an apple to your mouth, the biceps contract while the triceps relax. Inhibitory neurons are also thought to be involved in the state of muscle inhibition that occurs during the rapid eye movement (REM) stage of sleep.
To study the function of inhibitory neurons in more detail, the researchers used mice developed by Guoping Feng, the Poitras Professor of Neuroscience at MIT, in which all inhibitory spinal neurons were engineered to express an opsin called channelrhodopsin 2. This opsin stimulates neural activity when exposed to blue light. They then shone light at different points along the spine to observe the effects of neuron activation.
When inhibitory neurons in a small section of the thoracic spine were activated in freely moving mice, all hind-leg movement ceased. This suggests that inhibitory neurons in the thoracic spine relay the inhibition all the way to the end of the spine, Caggiano says. The researchers also found that activating inhibitory neurons had no effect on the transmission of sensory information from the limbs to the brain, or on normal reflexes.
“The spinal location where we found this complete suppression was completely new,” Caggiano says. “It has not been shown by any other scientists that there is this front-to-back suppression that affects only motor behavior without affecting sensory behavior.”
“It’s a compelling use of optogenetics that raises a lot of very interesting questions,” says Simon Giszter, a professor of neurobiology and anatomy at Drexel University who was not part of the research team. Among those questions is whether this mechanism behaves as a global “kill switch,” or if the inhibitory neurons form modules that allow for more selective suppression of movement patterns.
Now that they have demonstrated the usefulness of optogenetics for this type of study, the MIT team hopes to explore the roles of other types of spinal cord neurons. They also plan to investigate how input from the brain influences these spinal circuits.
“There’s huge interest in trying to extend these studies and dissect these circuits because we tackled only the inhibitory system in a very global way,” Caggiano says. “Further studies will highlight the contribution of single populations of neurons in the spinal cord for the control of limbs and control of movement.”

neurosciencestuff:

Controlling movement with light

For the first time, MIT neuroscientists have shown they can control muscle movement by applying optogenetics — a technique that allows scientists to control neurons’ electrical impulses with light — to the spinal cords of animals that are awake and alert.  

Led by MIT Institute Professor Emilio Bizzi, the researchers studied mice in which a light-sensitive protein that promotes neural activity was inserted into a subset of spinal neurons. When the researchers shone blue light on the animals’ spinal cords, their hind legs were completely but reversibly immobilized. The findings, described in the June 25 issue of PLoS One, offer a new approach to studying the complex spinal circuits that coordinate movement and sensory processing, the researchers say.

In this study, Bizzi and Vittorio Caggiano, a postdoc at MIT’s McGovern Institute for Brain Research, used optogenetics to explore the function of inhibitory interneurons, which form circuits with many other neurons in the spinal cord. These circuits execute commands from the brain, with additional input from sensory information from the limbs.

Previously, neuroscientists have used electrical stimulation or pharmacological intervention to control neurons’ activity and try to tease out their function. Those approaches have revealed a great deal of information about spinal control, but they do not offer precise enough control to study specific subsets of neurons.

Optogenetics, on the other hand, allows scientists to control specific types of neurons by genetically programming them to express light-sensitive proteins. These proteins, called opsins, act as ion channels or pumps that regulate neurons’ electrical activity. Some opsins suppress activity when light shines on them, while others stimulate it.

“With optogenetics, you are attacking a system of cells that have certain characteristics similar to each other. It’s a big shift in terms of our ability to understand how the system works,” says Bizzi, who is a member of MIT’s McGovern Institute.

Muscle control

Inhibitory neurons in the spinal cord suppress muscle contractions, which is critical for maintaining balance and for coordinating movement. For example, when you raise an apple to your mouth, the biceps contract while the triceps relax. Inhibitory neurons are also thought to be involved in the state of muscle inhibition that occurs during the rapid eye movement (REM) stage of sleep.

To study the function of inhibitory neurons in more detail, the researchers used mice developed by Guoping Feng, the Poitras Professor of Neuroscience at MIT, in which all inhibitory spinal neurons were engineered to express an opsin called channelrhodopsin 2. This opsin stimulates neural activity when exposed to blue light. They then shone light at different points along the spine to observe the effects of neuron activation.

When inhibitory neurons in a small section of the thoracic spine were activated in freely moving mice, all hind-leg movement ceased. This suggests that inhibitory neurons in the thoracic spine relay the inhibition all the way to the end of the spine, Caggiano says. The researchers also found that activating inhibitory neurons had no effect on the transmission of sensory information from the limbs to the brain, or on normal reflexes.

“The spinal location where we found this complete suppression was completely new,” Caggiano says. “It has not been shown by any other scientists that there is this front-to-back suppression that affects only motor behavior without affecting sensory behavior.”

“It’s a compelling use of optogenetics that raises a lot of very interesting questions,” says Simon Giszter, a professor of neurobiology and anatomy at Drexel University who was not part of the research team. Among those questions is whether this mechanism behaves as a global “kill switch,” or if the inhibitory neurons form modules that allow for more selective suppression of movement patterns.

Now that they have demonstrated the usefulness of optogenetics for this type of study, the MIT team hopes to explore the roles of other types of spinal cord neurons. They also plan to investigate how input from the brain influences these spinal circuits.

“There’s huge interest in trying to extend these studies and dissect these circuits because we tackled only the inhibitory system in a very global way,” Caggiano says. “Further studies will highlight the contribution of single populations of neurons in the spinal cord for the control of limbs and control of movement.”