The ability to learn associations between events is critical for survival, but it has not been clear how different pieces of information stored in memory may be linked together by populations of neurons. In a study published April 2nd in Cell Reports, synchronous activation of distinct neuronal ensembles caused mice to artificially associate the memory of a foot shock with the unrelated memory of exploring a safe environment, triggering an increase in fear-related behavior when the mice were re-exposed to the non-threatening environment. The findings suggest that co-activated cell ensembles become wired together to link two distinct memories that were previously stored independently in the brain.
“Memory is the basis of all higher brain functions, including consciousness, and it also plays an important role in psychiatric diseases such as post-traumatic stress disorder,” says senior study author Kaoru Inokuchi of the University of Toyama. “By showing how the brain associates different types of information to generate a qualitatively new memory that leads to enduring changes in behavior, our findings could have important implications for the treatment of these debilitating conditions.”
Recent studies have shown that subpopulations of neurons activated during learning are reactivated during subsequent memory retrieval, and reactivation of a cell ensemble triggers the retrieval of the corresponding memory. Moreover, artificial reactivation of a specific neuronal ensemble corresponding to a pre-stored memory can modify the acquisition of a new memory, thereby generating false or synthetic memories. However, these studies employed a combination of sensory input and artificial stimulation of cell ensembles. Until now, researchers had not linked two distinct memories using completely artificial means.
With that goal in mind, Inokuchi and Noriaki Ohkawa of the University of Toyama used a fear-learning paradigm in mice followed by a technique called optogenetics, which involves genetically modifying specific populations of neurons to express light-sensitive proteins that control neuronal excitability, and then delivering blue light through an optic fiber to activate those cells. In the behavioral paradigm, one group of mice spent six minutes in a cylindrical enclosure while another group explored a cube-shaped enclosure, and 30 minutes later, both groups of mice were placed in the cube-shaped enclosure, where a foot shock was immediately delivered. Two days later, mice that were re-exposed to the cube-shaped enclosure spent more time frozen in fear than mice that were placed back in the cylindrical enclosure.
The researchers then used optogenetics to reactivate the unrelated memories of the safe cylinder-shaped environment and the foot shock. Stimulation of neuronal populations in memory-related brain regions called the hippocampus and amygdala, which were activated during the learning phase, caused mice to spend more time frozen in fear when they were later placed back in the cylindrical enclosure, as compared with stimulation of neurons in either the hippocampus or amygdala, or no stimulation at all.
The findings show that synchronous activation of distinct cell ensembles can generate artificial links between unrelated pieces of information stored in memory, resulting in long-lasting changes in behavior. “By modifying this technique, we will next attempt to artificially dissociate memories that are physiologically connected,” Inokuchi says. “This may contribute to the development of new treatments for psychiatric disorders such as post-traumatic stress disorder, whose main symptoms arise from unnecessary associations between unrelated memories.”
More information: Cell Reports, Ohkawa et al.: “Artificial Association of Pre-Stored Information to Generate a Qualitatively New Memory” www.cell.com/cell-reports/abst… 2211-1247(15)00270-3
Scientists have built a light-weight wearable boot-like exoskeleton which reduces the energy needed for walking.
Researchers say the exoskeleton gives a 7% gain without chemical or electrical energy.
According to research published in the journal Nature, the energy saving is relatively modest but represents a considerable improvement on past designs.
Engineers have been trying to create machines since at least the 1890s to make walking easier but it is only recently that any attempt has met with success.
Steven Collins of the Department of Mechanical Engineering at Carnegie Mellon University and colleagues say the device acts in parallel with the user’s calf muscles, off-loading muscle force and reducing the energy consumed in contractions.
The device uses a mechanical clutch to hold a spring as it is stretched and relaxed by ankle movements when the foot is on the ground, helping to fulfil one function of the calf muscles and Achilles tendon.
People take about 10,000 steps a day or hundreds of millions of steps in a lifetime.
“While strong natural pressures have already shaped human locomotion, improvements in efficiency are still possible,” the study says. “Much remains to be learned about this seemingly simple behaviour.”
Watch the exoskeleton in action:
Of the mice that received the treatment, 75 percent got their memory functions back.
Australian researchers have come up with a non-invasive ultrasound technology that clears the brain of neurotoxic amyloid plaques – structures that are responsible for memory loss and a decline in cognitive function in Alzheimer’s patients.
If a person has Alzheimer’s disease, it’s usually the result of a build-up of two types of lesions – amyloid plaques, and neurofibrillary tangles. Amyloid plaques sit between the neurons and end up as dense clusters of beta-amyloid molecules, a sticky type of protein that clumps together and forms plaques.
Neurofibrillary tangles are found inside the neurons of the brain, and they’re caused by defective tau proteins that clump up into a thick, insoluble mass. This causes tiny filaments called microtubules to get all twisted, which disrupts the transportation of essential materials such as nutrients and organelles along them, just like when you twist up the vacuum cleaner tube.
As we don’t have any kind of vaccine or preventative measure for Alzheimer’s – a disease that affects 343,000 people in Australia, and 50 million worldwide – it’s been a race to figure out how best to treat it, starting with how to clear the build-up of defective beta-amyloid and tau proteins from a patient’s brain. Now a team from the Queensland Brain Institute (QBI) at the University of Queensland have come up with a pretty promising solution for removing the former.
Publishing in Science Translational Medicine, the team describes the technique as using a particular type of ultrasound called a focused therapeutic ultrasound, which non-invasively beams sound waves into the brain tissue. By oscillating super-fast, these sound waves are able to gently open up the blood-brain barrier, which is a layer that protects the brain against bacteria, and stimulate the brain’s microglial cells to activate. Microglila cells are basically waste-removal cells, so they’re able to clear out the toxic beta-amyloid clumps that are responsible for the worst symptoms of Alzheimer’s.
The team reports fully restoring the memory function of 75 percent of the mice they tested it on, with zero damage to the surrounding brain tissue. They found that the treated mice displayed improved performance in three memory tasks – a maze, a test to get them to recognise new objects, and one to get them to remember the places they should avoid.
“We’re extremely excited by this innovation of treating Alzheimer’s without using drug therapeutics,” one of the team, Jürgen Götz, said in a press release. “The word ‘breakthrough’ is often misused, but in this case I think this really does fundamentally change our understanding of how to treat this disease, and I foresee a great future for this approach.”
The team says they’re planning on starting trials with higher animal models, such as sheep, and hope to get their human trials underway in 2017.
You can hear an ABC radio interview with the team here.
In the first evidence of a natural intervention triggering stem cell-based regeneration of an organ or system, a study in the June 5 issue of the Cell Press journal Cell Stem Cell shows that cycles of prolonged fasting not only protect against immune system damage — a major side effect of chemotherapy — but also induce immune system regeneration, shifting stem cells from a dormant state to a state of self-renewal.
In both mice and a Phase 1 human clinical trial, long periods of not eating significantly lowered white blood cell counts. In mice, fasting cycles then “flipped a regenerative switch”: changing the signaling pathways for hematopoietic stem cells, which are responsible for the generation of blood and immune systems, the research showed.
The study has major implications for healthier aging, in which immune system decline contributes to increased susceptibility to disease as we age. By outlining how prolonged fasting cycles — periods of no food for two to four days at a time over the course of six months — kill older and damaged immune cells and generate new ones, the research also has implications for chemotherapy tolerance and for those with a wide range of immune system deficiencies, including autoimmunity disorders.
“We could not predict that prolonged fasting would have such a remarkable effect in promoting stem cell-based regeneration of the hematopoietic system,” said corresponding author Valter Longo, the Edna M. Jones Professor of Gerontology and the Biological Sciences at the USC Davis School of Gerontology, and director of the USC Longevity Institute.
“When you starve, the system tries to save energy, and one of the things it can do to save energy is to recycle a lot of the immune cells that are not needed, especially those that may be damaged,” Longo said. “What we started noticing in both our human work and animal work is that the white blood cell count goes down with prolonged fasting. Then when you re-feed, the blood cells come back. So we started thinking, well, where does it come from?”
Prolonged fasting forces the body to use stores of glucose, fat and ketones, but also breaks down a significant portion of white blood cells. Longo likens the effect to lightening a plane of excess cargo.
During each cycle of fasting, this depletion of white blood cells induces changes that trigger stem cell-based regeneration of new immune system cells. In particular, prolonged fasting reduced the enzyme PKA, an effect previously discovered by the Longo team to extend longevity in simple organisms and which has been linked in other research to the regulation of stem cell self-renewal and pluripotency — that is, the potential for one cell to develop into many different cell types. Prolonged fasting also lowered levels of IGF-1, a growth-factor hormone that Longo and others have linked to aging, tumor progression and cancer risk.
“PKA is the key gene that needs to shut down in order for these stem cells to switch into regenerative mode. It gives the ‘okay’ for stem cells to go ahead and begin proliferating and rebuild the entire system,” explained Longo, noting the potential of clinical applications that mimic the effects of prolonged fasting to rejuvenate the immune system. “And the good news is that the body got rid of the parts of the system that might be damaged or old, the inefficient parts, during the fasting. Now, if you start with a system heavily damaged by chemotherapy or aging, fasting cycles can generate, literally, a new immune system.”
Prolonged fasting also protected against toxicity in a pilot clinical trial in which a small group of patients fasted for a 72-hour period prior to chemotherapy, extending Longo’s influential past research: “While chemotherapy saves lives, it causes significant collateral damage to the immune system. The results of this study suggest that fasting may mitigate some of the harmful effects of chemotherapy,” said co-author Tanya Dorff, assistant professor of clinical medicine at the USC Norris Comprehensive Cancer Center and Hospital. “More clinical studies are needed, and any such dietary intervention should be undertaken only under the guidance of a physician.”
“We are investigating the possibility that these effects are applicable to many different systems and organs, not just the immune system,” said Longo, whose lab is in the process of conducting further research on controlled dietary interventions and stem cell regeneration in both animal and clinical studies.
- Chia-Wei Cheng, Gregor B. Adams, Laura Perin, Min Wei, Xiaoying Zhou, Ben S. Lam, Stefano Da Sacco, Mario Mirisola, David I. Quinn, Tanya B. Dorff, John J. Kopchick, Valter D. Longo. Prolonged Fasting Reduces IGF-1/PKA to Promote Hematopoietic-Stem-Cell-Based Regeneration and Reverse Immunosuppression. Cell Stem Cell, 2014; 14 (6): 810 DOI:1016/j.stem.2014.04.014
At some point in your life, you’ve probably been labeled a “right-brain thinker” (you’re so creative!) or a “left-brain thinker” (you’re so logical). Maybe this has shaped the way you see yourself or view the world.
“This is an idea that makes no physiological sense,” she says.
Blakemore believes that the concept of “logical, analytical, and accurate” thinkers favoring their left hemisphere and “creative, intuitive, and emotional” thinkers favoring their right hemisphere is the misinterpretation of valuable science. She thinks it entered pop culture because it makes for snappy self-help books. And of course people love categorizing themselves.
In the ’60s, ’70s, and ’80s, the renowned cognitive neuroscientist Michael Gazzaniga led breakthrough studies on how the brain works. He studied patients who — and here’s the key — lacked a corpus callosum, the tract that connect the brain’s hemispheres. During this time doctors had experimented on patients suffering from constant seizures due to intractable epilepsy by disconnecting the hemispheres.
Gazzaniga could thus determine the origins in the brain of certain cognitive and motor functions by monitoring the brains of these patients.
He found, for example, that a part of the left brain he dubbed “The Interpreter” handled the process of explaining actions that may have begun in the right brain.
He discovered “that each hemisphere played a role in different tasks and different cognitive functions, and that normally one hemisphere dominated over the other,” Blakemore explains.
This was breakthrough research on how parts of the brain worked. But in a normal human being, the corpus callosum is constantly transmitting information between both halves. It’s physically impossible to favor one side.
Blakemore thinks that this misinterpretation of the research is actually harmful, because the dichotomous labels convince people that their way of thinking is genetically fixed on a large scale.
“I mean, there are huge individual differences in cognitive strengths,” Blakemore says. “Some people are more creative; others are more analytical than others. But the idea that this has something to do with being left-brained or right-brained is completely untrue and needs to be retired.”
You can listen to Blakemore and many other experts taking down their least favorite ideas in the Freakonomics Radio episode “This Idea Must Die,” hosted by “Freakonomics” co-author Stephen J. Dubner.
The outlook used to be pretty bleak for those who had lost movement in their limbs due to severe nerve damage, but over the last year or so, some incredible advances have been made that are restoring shattered hope for many.
The amazing breakthroughs include spinal cord stimulation that allowed paralyzed men to regain some voluntary control of their legs, a brain implant that enabled a quadriplegic man to move his fingers, and a system that allowed a paralyzed woman to control a robotic armusing her thoughts. Science has definitely been on a roll, but this winning streak isn’t showing any signs of slowing down. Now, the world’s first “bionic reconstructions” have been performed on three Austrian men to help them regain hand function. This technique enabled the newly amputated patients to control prosthetic hands using their minds, allowing them to perform various tasks that most people take for granted.
The men that underwent the procedure had all suffered serious nerve damage as a result of car or climbing accidents, which left them with severely impaired hand function. The nerves that suffered injury were those within a network of fibers supplying the skin and muscles of the upper limbs, known as the brachial plexus. As lead researcher Professor Oskar Aszmann explains in a news release, traumatic events that sever these nerves are essentially inner amputations, irreversibly separating the limb from neural control. While it is possible to operate, Aszmann says the techniques are crude and do little to improve hand function. However, his newly developed procedure is quite different, and is proving to be a success.
Before the men could be fitted with their prosthetic hands, the researchers had to do some preliminary surgical work in which leg muscle was grafted into their arms in order to improve signal transmission from the remaining nerves. After a few months, the fibers had successfully innervated the transplanted tissue, meaning it was time to start the next stage: brain training.
Using a series of sensors placed onto the arm, the men slowly began to learn how to activate the muscle. Next, they mastered how to use electrical nerve signals to control a virtual hand, before eventually moving on to a hybrid hand that was affixed to their non-functioning hand. After around nine months of cognitive training, all of the men had their hand amputated and replaced with a robotic prosthesis that, via sensors, responds to electrical impulses in the muscles.
A few months later, the men had significantly improved hand movement control, which was highlighted by a test of function known as the Southampton Hand Assessment Procedure. As reported in The Lancet, before the procedure, the men scored an average of 9 out of 100, which soared to 65 using the prosthetic. Furthermore, the men reported less pain and a higher quality of life. For the first time since their injuries, they were able to perform avariety of tasks such as picking up objects, slicing food and undoing buttons with both hands.
“So far, bionic reconstruction has only been done in our center in Vienna,” said Aszmann. “However, there are no technical or surgical limitations that would prevent this procedure from being done in centers with similar expertise and resources.”
Think of it as interval training for the dinner table.University of Florida Health researchers have found that putting people on a feast-or-famine diet may mimic some of the benefits of fasting, and that adding antioxidant supplements may counteract those benefits.
Fasting has been shown in mice to extend lifespan and to improve age-related diseases. But fasting every day, which could entail skipping meals or simply reducing overall caloric intake, can be hard to maintain.
“People don’t want to just under-eat for their whole lives,” said Martin Wegman, an M.D.-Ph.D. student at the UF College of Medicine and co-author of the paper recently published in the journal Rejuvenation Research. “We started thinking about the concept of intermittent fasting.”
Michael Guo, a UF M.D.-Ph.D. student who is pursuing the Ph.D. portion of the program in genetics at Harvard Medical School, said the group measured the participants’ changes in weight, blood pressure, heart rate, glucose levels, cholesterol, markers of inflammation and genes involved in protective cell responses over 10 weeks.
“We found that intermittent fasting caused a slight increase to SIRT 3, a well-known gene that promotes longevity and is involved in protective cell responses,” Guo said.
The SIRT3 gene encodes a protein also called SIRT3. The protein SIRT3 belongs to a class of proteins called sirtuins. Sirtuins, if increased in mice, can extend their lifespans, Guo said. Researchers think proteins such as SIRT3 are activated by oxidative stress, which is triggered when there are more free radicals produced in the body than the body can neutralize with antioxidants. However, small levels of free radicals can be beneficial: When the body undergoes stress — which happens during fasting — small levels of oxidative stress can trigger protective pathways, Guo said.
“The hypothesis is that if the body is intermittently exposed to low levels of oxidative stress, it can build a better response to it,” Wegman said.
The researchers found that the intermittent fasting decreased insulin levels in the participants, which means the diet could have an anti-diabetic effect as well.
The group recruited 24 study participants in the double-blinded, randomized clinical trial. During a three-week period, the participants alternated one day of eating 25 percent of their daily caloric intake with one day of eating 175 percent of their daily caloric intake. For the average man’s diet, a male participant would have eaten 650 calories on the fasting days and 4,550 calories on the feasting days. To test antioxidant supplements, the participants repeated the diet but also included vitamin C and vitamin E.
At the end of the three weeks, the researchers tested the same health parameters. They found that the beneficial sirtuin proteins such as SIRT 3 and another, SIRT1, tended to increase as a result of the diet. However, when antioxidants were supplemented on top of the diet, some of these increases disappeared. This is in line with some research that indicates flooding the system with supplemental antioxidants may counteract the effects of fasting or exercise, said Christiaan Leeuwenburgh, Ph.D., co-author of the paper and chief of the division of biology of aging in the department of aging and geriatric research.
“You need some pain, some inflammation, some oxidative stress for some regeneration or repair,” Leeuwenburgh said. “These young investigators were intrigued by the question of whether some antioxidants could blunt the healthy effects of normal fasting.”
On the study participants’ fasting days, they ate foods such as roast beef and gravy, mashed potatoes, Oreo cookies and orange sherbet — but they ate only one meal. On the feasting days, the participants ate bagels with cream cheese, oatmeal sweetened with honey and raisins, turkey sandwiches, apple sauce, spaghetti with chicken, yogurt and soda — and lemon pound cake, Snickers bars and vanilla ice cream.
“Most of the participants found that fasting was easier than the feasting day, which was a little bit surprising to me,” Guo said. “On the feasting days, we had some trouble giving them enough calories.”
Leeuwenburgh said future studies should examine a larger cohort of participants and should include studying a larger number of genes in the participants as well as examining muscle and fat tissue.
- Martin P Wegman, Michael Guo, Douglas M Bennion, Meena N Shankar, Stephen M Chrzanowski, Leslie A Goldberg, Jinze Xu, Tiffany A Williams, Xiaomin Lu, Stephen I Hsu, Stephen D Anton, Christiaan Leeuwenburgh, Mark L Brantly.Practicality of Intermittent Fasting in Humans and its Effect on Oxidative Stress and Genes Related to Aging and Metabolism.Rejuvenation Research, 2014; 141229080855001 DOI: 1089/rej.2014.1624