caenorhabditis

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Take the connectome of a worm and transplant it as software in a Lego Mindstorms EV3 robot - what happens next?

It is a deep and long standing philosophical question: Are we just the sum of our neural networks? Of course, if you work in AI you take the answer mostly for granted, but until someone builds a human brain and switches it on we really don’t have a concrete example of the principle in action.

The nematode worm Caenorhabditis elegans (C. elegans) is tiny and only has 302 neurons. These have been completely mapped and the OpenWorm project is working to build a complete simulation of the worm in software. One of the founders of the OpenWorm project, Timothy Busbice, has taken the connectome and implemented an object oriented neuron program.

The model is accurate in its connections and makes use of UDP packets to fire neurons. If two neurons have three synaptic connections then when the first neuron fires a UDP packet is sent to the second neuron with the payload “3”. The neurons are addressed by IP and port number. The system uses an integrate and fire algorithm. Each neuron sums the weights and fires if it exceeds a threshold. The accumulator is zeroed if no message arrives in a 200ms window or if the neuron fires. This is similar to what happens in the real neural network, but not exact.

The software works with sensors and effectors provided by a simple LEGO robot. The sensors are sampled every 100ms. For example, the sonar sensor on the robot is wired as the worm’s nose. If anything comes within 20cm of the “nose” then UDP packets are sent to the sensory neurons in the network.

The same idea is applied to the 95 motor neurons but these are mapped from the two rows of muscles on the left and right to the left and right motors on the robot. The motor signals are accumulated and applied to control the speed of each motor. The motor neurons can be excitatory or inhibitory and positive and negative weights are used.

And the result?

It is claimed that the robot behaved in ways that are similar to observed C. elegans. Stimulation of the nose stopped forward motion. Touching the anterior and posterior touch sensors made the robot move forward and back accordingly. Stimulating the food sensor made the robot move forward.

The key point is that there was no programming or learning involved to create the behaviors. The connectome of the worm was mapped and implemented as a software system and the behaviors emerge.
The conectome may only consist of 302 neurons but it is self-stimulating and it is difficult to understand how it works - but it does.

Currently the connectome model is being transferred to a Raspberry Pi and a self-contained Pi robot is being constructed. It is suggested that it might have practical application as some sort of mobile sensor - exploring its environment and reporting back results. Given its limited range of behaviors, it seems unlikely to be of practical value, but given more neurons this might change.

Is the robot a C. elegans in a different body or is it something quite new? 

Is it alive?

Model Organisms Poster Illustration, gouache on watercolor paper 9x12″

Featuring (not drawn to scale) Xenopus laevis adult frog, oocytes, tadpoles and froglet; mus musculus (mouse); Escherichia coli (bacteria); Saccharomyces cerevisiae (budding yeast); Caenorhabditis elegans (roundworm); Drosophila melanogaster (fruit fly); Danio rerio (zebrafish); T4 phage (virus); and Rattus norvegicus (brown rat).

More of my art can be found on my etsy and my deviantart

Illuminating neuron activity in 3-D

Researchers at MIT and the University of Vienna have created an imaging system that reveals neural activity throughout the brains of living animals. This technique, the first that can generate 3-D movies of entire brains at the millisecond timescale, could help scientists discover how neuronal networks process sensory information and generate behavior.

The team used the new system to simultaneously image the activity of every neuron in the worm Caenorhabditis elegans, as well as the entire brain of a zebrafish larva, offering a more complete picture of nervous system activity than has been previously possible.

“Looking at the activity of just one neuron in the brain doesn’t tell you how that information is being computed; for that, you need to know what upstream neurons are doing. And to understand what the activity of a given neuron means, you have to be able to see what downstream neurons are doing,” says Ed Boyden, an associate professor of biological engineering and brain and cognitive sciences at MIT and one of the leaders of the research team. “In short, if you want to understand how information is being integrated from sensation all the way to action, you have to see the entire brain.”

The new approach, described May 18 in Nature Methods, could also help neuroscientists learn more about the biological basis of brain disorders. “We don’t really know, for any brain disorder, the exact set of cells involved,” Boyden says. “The ability to survey activity throughout a nervous system may help pinpoint the cells or networks that are involved with a brain disorder, leading to new ideas for therapies.”

Boyden’s team developed the brain-mapping method with researchers in the lab of Alipasha Vaziri of the University of Vienna and the Research Institute of Molecular Pathology in Vienna. The paper’s lead authors are Young-Gyu Yoon, a graduate student at MIT, and Robert Prevedel, a postdoc at the University of Vienna.

High-speed 3-D imaging

Neurons encode information — sensory data, motor plans, emotional states, and thoughts — using electrical impulses called action potentials, which provoke calcium ions to stream into each cell as it fires. By engineering fluorescent proteins to glow when they bind calcium, scientists can visualize this electrical firing of neurons. However, until now there has been no way to image this neural activity over a large volume, in three dimensions, and at high speed.

Scanning the brain with a laser beam can produce 3-D images of neural activity, but it takes a long time to capture an image because each point must be scanned individually. The MIT team wanted to achieve similar 3-D imaging but accelerate the process so they could see neuronal firing, which takes only milliseconds, as it occurs.

The new method is based on a widely used technology known as light-field imaging, which creates 3-D images by measuring the angles of incoming rays of light. Ramesh Raskar, an associate professor of media arts and sciences at MIT and an author of this paper, has worked extensively on developing this type of 3-D imaging. Microscopes that perform light-field imaging have been developed previously by multiple groups. In the new paper, the MIT and Austrian researchers optimized the light-field microscope, and applied it, for the first time, to imaging neural activity.

With this kind of microscope, the light emitted by the sample being imaged is sent through an array of lenses that refracts the light in different directions. Each point of the sample generates about 400 different points of light, which can then be recombined using a computer algorithm to recreate the 3-D structure.

“If you have one light-emitting molecule in your sample, rather than just refocusing it into a single point on the camera the way regular microscopes do, these tiny lenses will project its light onto many points. From that, you can infer the three-dimensional position of where the molecule was,” says Boyden, who is a member of MIT’s Media Lab and McGovern Institute for Brain Research.

Prevedel built the microscope, and Yoon devised the computational strategies that reconstruct the 3-D images.

Aravinthan Samuel, a professor of physics at Harvard University, says this approach seems to be an “extremely promising” way to speed up 3-D imaging of living, moving animals, and to correlate their neuronal activity with their behavior. “What’s very impressive about it is that it is such an elegantly simple implementation,” says Samuel, who was not part of the research team. “I could imagine many labs adopting this.”

Neurons in action

The researchers used this technique to image neural activity in the worm C. elegans, the only organism for which the entire neural wiring diagram is known. This 1-millimeter worm has 302 neurons, each of which the researchers imaged as the worm performed natural behaviors, such as crawling. They also observed the neuronal response to sensory stimuli, such as smells.

The downside to light field microscopy, Boyden says, is that the resolution is not as good as that of techniques that slowly scan a sample. The current resolution is high enough to see activity of individual neurons, but the researchers are now working on improving it so the microscope could also be used to image parts of neurons, such as the long dendrites that branch out from neurons’ main bodies. They also hope to speed up the computing process, which currently takes a few minutes to analyze one second of imaging data.

The researchers also plan to combine this technique with optogenetics, which enables neuronal firing to be controlled by shining light on cells engineered to express light-sensitive proteins. By stimulating a neuron with light and observing the results elsewhere in the brain, scientists could determine which neurons are participating in particular tasks.

How Young Brains Form Lifelong Memories

Members of neuroscientist Cori Bargmann’s lab spend quite a bit of their time watching worms move around. These tiny creatures, Caenorhabditis elegans, feed on soil bacteria, and their very lives depend on their ability to distinguish toxic microbes from nutritious ones. In a recent study, Bargmann and her colleagues have shown that worms in their first larval stage can learn what harmful bacterial strains smell like, and form aversions to those smells that last into adulthood.

The research is in Cell. (full access paywall)

(Image caption: This image shows a single sensory neuron in the roundworm Caenorhabditis elegans. Salk researchers demonstrated how a neural circuit uses prior experience to modify future behaviors. The work reveals new details on the function of two chemical signals critical to animal–and human–behavior: dopamine (responsible for reward and risk-taking) and CREB (needed for learning). Credit: Salk Institute for Biological Studies)

How the brain balances risk-taking and learning

If you had 10 chances to roll a die, would you rather be guaranteed to receive $5 for every roll ($50 total) or take the risk of winning $100 if you only roll a six?

Most animals, from roundworms to humans, prefer the more predictable situation when it comes to securing resources for survival, such as food. Now, Salk scientists have discovered the basis for how animals balance learning and risk-taking behavior to get to a more predictable environment. The research reveals new details on the function of two chemical signals critical to human behavior: dopamine–responsible for reward and risk-taking–and CREB–needed for learning. 

“Previous research has shown that certain neurons respond to changes in light to determine variability in their environment, but that’s not the only mechanism,” says senior author Sreekanth Chalasani, an assistant professor in Salk’s Molecular Neurobiology Laboratory. “We discovered a new mechanism that evaluates environmental variability, a skill crucial to animals’ survival.”

By studying roundworms (Caenorhabditis elegans), Salk researchers charted how this new circuit uses information from the animal’s senses to figure out how predictable the environment and prompt the worm to move to a new location if needed. The work was detailed April 9, 2015 in Neuron.

The circuit, made up of 16 of the 302 neurons in the worm’s brain, likely has parallels in more complex animal brains, researchers say, and could be a starting point to understanding–and fixing–certain psychiatric or behavioral disorders.

“What was surprising is the degree to which variability in animal behavior can be explained by variability in their past sensory experience and not just noise,” says Tatyana Sharpee, associate professor and co-senior author of the paper. “We can now predict future animal behaviors based on past sensory experience, independent of the influence of genetic factors.”

The team discovered that two pairs of neurons in this learning circuit act as gatekeepers. One pair responds to large increases of the presence of food and the other pair responds to large decreases of the presence of food. When either of these high-threshold neurons detect a large change in an environment (for example, the smell of a lot of food to no food) they induce other neurons to release the neurotransmitter dopamine.

Dumping dopamine onto a brain–human or otherwise–makes one more willing to take risks. It’s no different in the roundworm: stimulated by large varieties in its environment, dopamine surges in the worm’s system and activates four other neurons in the learning circuit, giving them a greater response range. This prompts the worm to search more actively in a wider area (risk-taking) until it hits a more consistent environment. The amount of dopamine in its system serves as its memory of the past experience: about 30 minutes or so and it forgets information gathered in the time before that.

While it’s been known that the presence of dopamine is tied to risk-taking behavior, how exactly dopamine does this hasn’t been well understood. With this new work, scientists now have a fundamental model of how dopamine signaling leads the worm to take more risks and explore new environments.

“The connection between dopamine and risk is conserved across animals and is already known, but we showed mechanistically how it works,” says Chalasani, who is also holder of the Helen McLoraine Developmental Chair in Neurobiology. “We hope this work will lead to better therapies for neurodegenerative and behavioral diseases and other disorders where dopamine signaling is irregular.”

Interestingly, the scientists found that the high-threshold neurons also lead to increased signaling from a protein called CREB, known in humans and other animals to be essential to learning and retaining new memories. The researchers showed that not only are the presence of CREB important to learning, but the amount of CREB protein determines how quickly an animal learns. This surprising connection could lead to new avenues of research for brain enhancements, adds Chalasani.

How did researchers test all of this in worms exactly? They began by placing worms in dishes that contained either a large or a small patch of edible bacteria. Worms in the smaller patches tended to reach the edges more frequently, experiencing large changes in variability (edges have large amounts of food compared to the center). Worms on the large patch, however, reached the edge less frequently, thereby experiencing a general stable environment (mainly an area with constant food).

Using genetics, imaging, behavioral analysis and other techniques, researchers found that when worms are on small patches, the two pairs of high-threshold neurons respond to the greater variation and signal leading to increased dopamine. When worms in these smaller patches (and higher dopamine) were taken out and put into a new dish, they explored a larger area, taking more of a risk. Worms from the larger patches, however, produced less dopamine and were more cautious, exploring just a small space when placed in a new area.

Additionally, when the protein CREB was present in larger amounts, the team found that the worms took far less time to learn about their food variability. “Normally the worms took about 30 minutes or so to explore and learn about food, but as you keep increasing the CREB protein they learn it faster,” says Chalasani. “So dopamine stores the memory of what these worms learn while CREB regulates how quickly they learn.”

The florid crown of Utricularia vulgaris, who by means of creating a negative pressure region within tiny sacks in the water, via active osmosis, sucks in prey in under a 100th of a second.  One of the most successful plants within the carnivorous flora niche.  Quite beautiful flowers for us to look at, but if your a Daphnia (water flea) or Caenorhabditis elegans (nematode) then watch out. 

Model organism Caenorhabditis elegans.

Global Regulator of mRNA Editing Found
Protein controls editing, expanding the information content of DNA

An international team of researchers, led by scientists from the University of California, San Diego School of Medicine and Indiana University, have identified a protein that broadly regulates how genetic information transcribed from DNA to messenger RNA (mRNA) is processed and ultimately translated into the myriad of proteins necessary for life.

The findings, published today in the journal Cell Reports, help explain how a relatively limited number of genes can provide versatile instructions for making thousands of different messenger RNAs and proteins used by cells in species ranging from sea anemones to humans. In clinical terms, the research might also help researchers parse the underlying genetic mechanisms of diverse diseases, perhaps revealing new therapeutic targets.

“Problems with RNA editing show up in many human diseases, including those of neurodegeneration, cancer and blood disorders,” said Gene Yeo, PhD, assistant professor in the Department of Cellular and Molecular Medicine at UC San Diego. “This is the first time that a single protein has been identified that broadly regulates RNA editing. There are probably hundreds more. Our approach provides a method to screen for them and opens up new ways to study human biology and disease.”

“To be properly expressed, all genes must be carefully converted from DNA to messenger RNA, which can then be translated into working proteins,” said Heather Hundley, PhD, assistant professor of biochemistry and molecular biology at Indiana University and co-senior author of the study. RNA editing alters nucleotides (the building blocks of DNA and RNA) within the mRNA to allow a single gene to create multiple mRNAs that are subject to different modes of regulation. How exactly this process can be modulated, however, has never been clear.

Using the nematode Caenorhabditis elegans as their model organism and a novel computational framework, Hundley, Yeo and colleagues identified more than 400 new mRNA editing sites – the majority regulated by a single protein called ADR-1, which does not directly edit mRNA but rather regulated how editing occurred by binding to the messenger RNAs subject to editing.

“Cells process their genetic code in a way analogous to how the programming language Java compiles modern software. Both systems use an intermediate representation that is modified depending on its environment” said co-first author Boyko Kakaradov, a bioinformatics PhD student in the Yeo lab. “We’re now finding how and why the mRNA code is being changed en route to the place of execution.”

The scientists noted that a protein similar to ADR-1 is expressed by humans, and that many of the same mRNA targets exist in people too. “So it is likely that a similar mechanism exists to regulate editing in humans,” said Hundley, adding that she and colleagues will now turn to teasing out the specifics of how proteins like ADR-1 regulate editing and how they might be exploited “to modulate editing for the treatment of human diseases.”  

(Image caption: The image shows a head of a roundworm whose nerve cells have been genetically modified to glow under the microscope. The image is superimposed onto a typical activity measurement from some of these cells. The scientists were able to decode the worm’s behavioral intents from such measurements.)

Neuroscientists decode the brain activity of the worm

Manuel Zimmer and his team at the Research Institute of Molecular Pathology (IMP) present new findings on the brain activity of the roundworm Caenorhabditis elegans. The scientists were able to show that brain cells (neurons), organized in a brain-wide network, albeit exerting different functions, coordinate with each other in a collective manner. They could also directly link these coordinated activities in the worm’s brain to the processes that generate behavior. The results of the study are presented in the current issue of the journal Cell.

One of the major goals of neuroscience is to unravel how the brain functions in its entirety and how it generates behavior. The biggest challenge in solving this puzzle is represented by the sheer complexity of nervous systems. A mouse brain, for example, consists of millions of neurons linked to each other in a highly complex manner. In contrast to that, the nematode Caenorhabditis elegans is equipped with a nervous system comprised of only 302 neurons. Due to its easy handling and its developmental properties, this tiny, transparent worm has become one of the most important model organisms for basic research. For almost 30 years, the list of connections between individual neurons has been known. Despite the low number of neurons, its neuronal networks possesse a high degree of complexity and sophisticated behavioral output; the worm thus represents an animal of choice to study brain function.

Interplay of neuronal groups in brain-wide networks

Researchers have mostly concentrated on studying the functions of single or a handful of neural cells and some of their interactions to explain behavior such as movements. For the worm, it has been known how some single neurons function as isolated units within the network, but it remained unknown how they work together as a group. Manuel Zimmer, a group leader at the IMP, wanted to address this unsolved question in his research. Together with his team, he combined two state-of-the-art technologies for the current study: first, the scientists used 3D microscopy techniques to simultaneously and rapidly measure different regions of the brain; second, they used worms genetically engineered with a fluorescent protein that caused the worm’s neurons to flash when they were active. “This combination was brilliant for us, as it allowed a brain-wide single-cell resolution of our recordings in real time,” Zimmer explains the advantages of this approach.

Reading the worm’s mind

Zimmer and his team tested the animals‘ reaction to stimuli from outside when they were trying to find food. Under the microscope, a fascinating picture was revealed to the researchers: “We saw that most of the neurons are constantly active and coordinate with each other in a brain-wide manner. They act as an ensemble”, explains postdoctoral scientist Saul Kato, who spearheaded the study together with Harris Kaplan and Tina Schrödel, graduate students in the Zimmer laboratory. The animals were immobilized for these experiments, their reactions therefore representing intentions as opposed to reflecting actual movement.

With a different technique of microscopy, set up for freely moving worms, the scientists were able to detect the neurons that initiate movement. There was a direct correlation between the activity of certain networks and the impulse for movements; thus Zimmer and his co-workers could literally watch the worms think. These network activities not only represented short movements, but also their assembly into longer lasting behavioral strategies such as foraging. “This is something that no one has managed to do before”, Zimmer points out. Suggestions of similar patterns of neural activity have been found in higher animals, but so far only a fraction of neurons in sub-regions of the brain could be examined at the same time. Zimmer and his colleagues are therefore confident that their results represent basic principles of brain function, even though the worm is only distantly related to mammals.

Investigation of molecular mechanisms

Many questions in the area of neurobiology remain largely unsolved, such as how decisions are made or whether the brain operates in a formal algorithmic manner, like a computer. In the next phase of research, Manuel Zimmer intends to analyze the molecular mechanisms underlying the processes he investigated. “It would also be interesting to have a closer look at long lasting brain states such as sleep and waking”, he says, laying out his ambitious plans for the future.

Researchers Use Sound Waves to Control Brain Cells

Salk scientists have developed a new way to selectively activate brain, heart, muscle and other cells using ultrasonic waves. The new technique, dubbed sonogenetics, has some similarities to the burgeoning use of light to activate cells in order to better understand the brain.

The research is in Nature Communications. (full open access)

Research: “Sonogenetics is a non-invasive approach to activating neurons in Caenorhabditis elegans” by Stuart Ibsen, Ada Tong, Carolyn Schutt, Sadik Esener and Sreekanth H. Chalasani in Nature Communications doi:10.1038/ncomms9264

Image: For the first time, sound waves are used to control brain cells. Salk scientists developed the new technique, dubbed sonogenetics, to selectively and noninvasively turn on groups of neurons in worms that could be a boon to science and medicine. Credit: Salk Institute for Biological Studies.

WATCH: Scientists Just Put A Worm’s Brain Into A Robot’s Body%

A brain is just electrical signals. If you can map those signals, you can transfer one’s brain patterns. And that’s exactly what scientists have done.

This Lego robot is entirely controlled by a virtual nematode brain…
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When looking at the most complex machine known to man, the brain, in the end, it’s nothing more than a collection of electrical signals. This means that, if we can accurately catalog those signals, then we can implant them into something else. Perhaps another person, transferring memories, dreams, and everything else that makes you, well, you. Along these same lines, you could upload the signals into a machine, turning the computer into a synthetic version of life.

And now, researchers have managed to do this with the roundworm Caenorhabditis elegans. Researchers from the OpenWorm project have successfully mapped all the connections between the worm’s 302 neurons and managed to simulate them in software (a little robot). The roundworm brain has just 1000 cells, of which only 302 are neurons and 7,000 connections or synapses. If you are wondering, the human brain has an estimated 86 billion neurons. So trying this on humans is a long, long way off.

True, this might seem like a strange feat (and it is), but such experiments help us work toward accomplishing this with more complex organisms—so perhaps someday Doctor Who’s K-9 will be possible. And more importantly, this research is helping us better understand how brains work on the whole, which could lead to more effective treatment, or maybe even a cure, for diseases such as Alzheimer’s.

The information that scientists have gathered over the last few decades has allowed scientists to create what is called a “connectome” for the worm. A connectome is a detailed map that shows how a animal is structured cell by cell. Now that information has been, in part, recreated digitally,

The researchers do note that this is just a first, baby-step. The brain simulation still isn’t 100% exact, as the researchers had to simplify the process that triggers an artificial neuron to fire (that’s right, we still can’t fully replicate even a roundworm’s brain). But as previously mentioned, it is a notable first step.

“Because we believe brain research must accelerate, we are taking matters into our own hands. If we cannot build a computer model of a worm, the most studied organism in all of biology, we don’t stand a chance to understand something as complex as the human brain. We must crawl before we can walk!” OpenWorm explains on their website.

The ultimate goal of the project is to completely replicate the roundworm and make it into a fully virtual organism; however, at the present juncture, they’ve only managed to simulate its brain, and they’ve now uploaded that into a simple Lego robot.

SEE A VIDEO OF IT IN ACTION:
http://bit.ly/1wtzn6q

Nothing to Squirm About: Space Station Worms Help Battle Muscle and Bone Loss
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ISS - International Space Station patch.

January 16, 2015

It is said that great things can come in small packages. In this case, one key to keeping astronauts healthy on long-duration space missions may be found in a tiny roundworm barely a millimeter long.

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Image above: Caenorhabditis elegans – a millimeter-long roundworm with a genetic makeup scientists understand – will be central to a pair of Japan Aerospace Agency investigations into muscle and bone loss of astronauts on the International Space Station in the first few months of 2015. Image Credit: NASA.

Two Japan Aerospace Exploration Agency (JAXA) investigations on the International Space Station help researchers seek clues to physiological problems found in astronauts by studying Caenorhabditis elegans – a millimeter-long roundworm that, like the fruit fly, is widely used as a model for larger organisms. The results of the investigation could lead to new treatments for bone and muscle loss in humans living in space. Findings may also be beneficial to people on Earth suffering from muscle and bone diseases.

“Spaceflight-induced health changes, such as decreases in muscle and bone mass, are a major challenge facing our astronauts,” said Julie Robinson, NASA’s Chief Scientist for the International Space Station Program Office at NASA’s Johnson Space Center in Houston. “We investigate solutions on the station not only to keep astronauts healthy as the agency considers longer space exploration missions, but also to help those on Earth who have limited activity as a result of aging or illness.”

We rely on gravity to develop stronger muscles and bones. Athletes will lift weights – resisting the pull of gravity – to make their bodies even stronger. When gravity is greatly reduced – as in spaceflight – we don’t use those muscles to resist the force of gravity, and muscles and bones can slowly start to deteriorate. Even with assigned daily exercise, the bodies of astronauts in microgravity lose bone and muscle mass.

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International Space Station. Image Credit: NASA
This is the same problem facing people who are on prolonged bed rest. The inactivity, even removing simple daily movement, can have a negative effect on the bones and muscles of the infirm or elderly. Patients on prolonged bed rest experience muscle atrophy, bone density loss and changes in metabolism, similar to the effects of long-duration spaceflight.

One investigation, scheduled for launch to the station on the SpaceX’s sixth space station resupply mission in 2015, is called Alterations of C. elegans muscle fibers by microgravity (Nematode Muscle). It will look into the muscle fibers and cytoskeleton of the roundworm to clarify how those physiological systems alter in response to microgravity. Space station crew members will grow these worms in microgravity, as well as another batch in one-g using a centrifuge. This will simulate the force of gravity while the C. elegans remain physically in orbit, allowing a direct comparison of the effects of different gravity levels on organisms in space.

A different JAXA investigation currently on station is taking a much closer look at C. elegans by examining their DNA. The Epigenetics in spaceflown C. elegans (Epigenetics) study launched to the space station on the SpaceX CRS-5 resupply mission. It requires astronauts on the orbiting laboratory to grow four generations of the worm, with adults and larvae from each generation preserved at different points during their lifespan. The worms will return to Earth in the SpaceX Dragon spacecraft in January.

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Image above: A researcher prepares samples of the Japan Aerospace Exploration Agency’s Epigenetics investigation at the Kennedy Space Center in Florida for launch on the fifth SpaceX resupply mission to the International Space Station. Image Credit: JAXA/Tohoku University.

“The astronauts will cultivate multiple generations of the organism, so we can examine the organisms in different states of development,” said Atsushi Higashitani, principal investigator for both investigations with Tohoku University in Miyagi, Japan. “Our studies will help clarify how and why these changes to health take place in microgravity and determine if the adaptations to space are transmitted from one cell generation to another without changing the basic DNA of an organism. Then, we can investigate if those effects could be treated with different medicines or therapies.”

Worms grown in each investigation will be compared to similar batches grown in a laboratory in Japan. Understanding the molecular changes that take place in microgravity could help researchers develop treatments or therapies to counteract the physical changes associated with aging and extended bed rest, such as muscle atrophy or osteoporosis, and could help develop treatments or exercises for astronauts on long voyages.

This simple, tiny roundworm could lead to a cure for symptoms affecting millions of the aging and infirm population of Earth, and the astronauts orbiting it, potentially offering a solution to a major problem in an extremely small package.

Related links:

Japan Aerospace Exploration Agency (JAXA): http://global.jaxa.jp/

Model for larger organisms: https://blogs.nasa.gov/ISS_Science_Blog/2013/11/13/model-organisms-shining-examples-for-simple-effective-biology-research/

The Epigenetics in spaceflown C. elegans (Epigenetics) study: http://www.nasa.gov/mission_pages/station/research/experiments/1075.html

SpaceX CRS-5 resupply mission: http://www.nasa.gov/mission_pages/station/research/news/spacex_cats

For more information about the International Space Station (ISS), visit: http://www.nasa.gov/mission_pages/station/main/index.html

Images (mentioned), Text, Credits: NASA/International Space Station Program Science Office, By Bill Hubscher/NASA’s Marshall Space Flight Center.

Best regards, Orbiter.ch
Full article
Scientists learn how young brains form lifelong memories by studying worms’ food choices

Members of neuroscientist Cori Bargmann’s lab spend quite a bit of their time watching worms move around. These tiny creatures, Caenorhabditis elegans, feed on soil bacteria, and their very lives depend on their ability to distinguish toxic microbes from nutritious ones. In a recent study, Bargmann and her colleagues have shown that worms in their first larval stage can learn what harmful bacterial strains smell like, and form aversions to those smells that last into adulthood.

(Image caption: Lasting impressions: A segment of a C. elegans worm with a RIM neuron shown in green. The scientists showed that this neuron produces a learning signal that makes the newly hatched worm able to remember an olfactory experience for the rest of its life)

Many animals are capable of making vital, lifelong memories during a critical period soon after birth. The phenomenon, known as imprinting, allows newly hatched geese to bond with their moms, and makes it possible for salmon to return to their native stream after spawning. And while the learning processes of humans may be more complex and subtle, scientists have long known that our brain’s ability to store a memory and maintain it long-term depends on when and how that memory was acquired.

“In the case of worms, we were fascinated to discover that their small and simple nervous system is capable of not only remembering things, but of forming long-term memories,” says Bargmann, who is Torsten N. Wiesel Professor and head of the Lulu and Anthony Wang Laboratory of Neural Circuits and Behavior, as well as co-director of the new Kavli Neural Systems Institute at Rockefeller. “It invites the question of whether learning processes that happen during different life stages are biologically different.”

In the study, she and Rockefeller graduate student Xin Jin let both young and adult worms learn to avoid food smells, and studied in detail the neural circuits that produced memories of the experience. Their findings, published in Cell, clarify which neurons, genes, and molecular pathways distinguish the two types of memory, providing new vistas into the neurobiology of learning.

Imprinted aversions last a lifetime

When adult C. elegans worms encounter pathogenic bacteria, they avoid it by moving in the opposite direction, and they shun similar bacteria for about 24 hours. But their memory soon fades.

Young worms, on the other hand, form more lasting impressions. The researchers allowed newborn worms to hatch directly onto a lawn of pathogens, and left them there for their first 12 hours of life—the first larval stage. (The bugs gave the worms intestinal infections, but didn’t kill them.) Then, when the worms encountered the pathogens again as adults—three days later—they fled. Worms that hadn’t been hatched onto poisonous bacteria found them just as attractive as harmless ones.

Jin found that by silencing specific neurons in the worms, and repeating the learning assays, she was able to determine each nerve cell’s contribution to the memory process. The results of her experiments show that the neural circuits that mediate the two types of learning are similar, but not identical. Many neurons are needed for both imprinted and adult learning, but cells called AIB and RIM are uniquely important for the formation of the imprinted memory during the larval stage.

A similar picture emerged when the researchers compared the genes and signaling pathways that are activated when worms form imprinted versus short-term memories. The two processes rely on similar molecular components, but some genes were found to be specifically required for only one type of learning.

“These findings suggest that early imprinting isn’t totally different from other learning—it’s the same system enhanced with some special features,” Bargmann says.

How memories are formed, stored, and retrieved

Several neurological processes are at play when we learn new things. For example, when a baby songbird learns a song from an adult bird, a memory of the tutor’s performance must first form and be stored in his brain. Then, when it’s time for the bird to debut with his own song, that memory must be retrieved to practice and then perform a vocal behavior.

Because most animals’ brains are very complex, it has been difficult for scientists to study these elements of learning in detail. By using C. elegans, whose modest brain has only 302 neurons, the researchers were able to shed light on the neural circuits that drive the formation and retrieval of a worm’s memory—and the two processes turned out to be neurologically distinct.

“We learned that when worms form an early memory of a food smell, they use one set of neurons to plant that memory,” Bargmann says, “and later in life, when they encounter the same smell again, they use a different set of neurons to pull the memory out.”

How memories are stored in the brain—in what neurons they reside and what constitutes them at the molecular level—remains elusive. But Bargmann says her lab’s findings have laid the groundwork for future research into stored memory and other open questions.

“The most evocative thing about this work is that it reminds us that learning isn’t some fancy innovation of a complex brain,” she says. “It’s a fundamental function that any nervous system can perform.”

Gene discovery prevents weight gain with a high-sugar diet

Imagine being able to take a pill that lets you eat all of the ice cream, cookies, and cakes that you wanted – without gaining any weight.

C. elegans, a one-millimeter-long worm that scientists have used as a model organism since the 1970s. Courtesy of the Curran Laboratory

New research from USC suggests that dream may not be impossible. A team of scientists led by Sean Curran of the USC Davis School of Gerontology and the Keck School of Medicine of USC found a new way to suppress the obesity that accompanies a high-sugar diet, pinning it down to a key gene that pharmaceutical companies have already developed drugs to target.

So far, Curran’s work has been solely on the worm Caenorhabditis elegans and human cells in a petri dish – but the genetic pathway he studied is found in almost all animals from yeast to humans. Next, he plans to test his findings in mice.

Curran’s research is outlined in a study that will be published on Oct. 6 by Nature Communications.

Building on previous work with C. elegans, Curran and his colleagues found that certain genetic mutants – those with a hyperactive SKN-1 gene – could be fed incredibly high-sugar diets without gaining any weight, while regular C. elegans ballooned on the same diet.

“The high-sugar diet that the bacteria ate was the equivalent of a human eating the Western diet,” Curran said, referring to the diet favored by the Western world, characterized by high-fat and high-sugar foods, like burgers, fries and soda.

The SKN-1 gene also exists in humans, where it is called Nrf2, suggesting that the findings might translate, he said. The Nrf2 protein, a “transcription factor” that binds to a specific sequence of DNA to control the ability of cells to detox or repair damage when exposed to chemically reactive oxygen (a common threat to cells’ well being), has been well studied in mammals.

Pharmaceutical companies have already worked to develop small-molecule drugs that target Nrf2, in hopes that it will produce more anti-oxidants and slow aging.

Though the promise of a pill to help control your body’s response to food is enticing, it is not without risk, Curran said. Increased Nrf2 function has been linked to aggressive cancers.

“Perhaps it is a matter of timing and location,” Curran said. “If we can acutely activate Nrf2 in specific tissues when needed then maybe we can take advantage of its potential benefits.”

Linking genes with actions, thanks to worms

Researchers from the MRC’s Clinical Sciences Centre at Imperial College London have developed a pioneering tool to analyse a worm’s posture as it wriggles.

Using the new tool, the team investigated how exactly the worm’s brain controls its movements. This could give insight into how differences in genes can change neuronal activity in the brains, not just of worms, but of humans too.

Recent advances in technology mean that scientists are now able to gather huge amounts of data about the genes associated with movement and about the activity of nerve cells, or neurons, which drive that activity – whether in worms or in people. But the challenge is to integrate this data with other observations, in a meaningful way.

This new research begins, for the first time, to develop a bigger picture of the whole system of movement, working as one.

The researchers created a library of shapes such that each depicts a key posture adopted by Caenorhabditis elegans (C.elegans) – a type of tiny nematode worm that is a mainstay of scientific research.

C.elegans is the only animal for which scientists have established how all of its neurons are connected. It is also a good model for the human brain because some of the genes that encode its neurons can be found in people, and many of the molecules that its neurons use to communicate with each other, such as dopamine and serotonin, are thought to play similar roles in the human brain.

“Worms are a testing ground,” says Andre Brown, who is head of the Behavioural Genomics group at the Centre and who led the research. “We still don’t know the best ways to measure behaviour. We think that what we learn from studying worms will also help with more complex organisms, and ultimately influence how we measure human behaviours.”

The worms move by bending sections of their body in turn, to create a wave of movement. Brown and his team have developed an automated camera to track a worm’s movement. It takes 30 static images of the worm’s shape, or posture, every second, to capture even subtle changes.

A computer then assigns the posture a numerical value between 1 and 90, each of which denotes a benchmark posture. The sequence of postures that a worm adopts over time is then represented by a string of numbers.

This numerical data can then be linked to information from separate studies on the worms’ genes and neuronal activity, to try to spot any associations between posture, neuronal activity and genes.

Using such techniques to study the entire process of movement – muscles contracting and relaxing in response to signals from the brain – in worms, they may one day be able to extend them to human movement and other brain processes.

By understanding more about the brain works in a healthy person, the hope is to find clues to what goes wrong in conditions such as depression, anxiety and schizophrenia, though that is a long way off.

The scientists say that their inspiration for studying the building blocks of behaviour came from patterns in language, where words are repeated in different sequences to create sentences. Behaviours, they suggest, are made up of a similar sequence of repeated movements.

Researchers at the MRC’s Laboratory of Molecular Biology in Cambridge, and the European Bioinformatics Institute in Hinxton, worked with Brown on the study published in PLOS Biology. Together they monitored the movement of 18 strains of worms from across the world, each with slightly different genes. They found that the worms’ postures varied between strains, much as people’s accents can vary between regions.

Linking each worm’s ‘accent’ to the genes of that strain could also hold clues to a better understanding of the genes and neurons behind behaviours. One day, scientists may be able to make similar links in humans.

(Image caption: Pictured is a worm, called C. elegans, changing direction in a beautiful movement known as an ‘omega turn.’)

State-of-the-art integrated imaging system allows scientists to map brain cells responsible for memory

Scientists from Kyoto University’s Institute for Integrated Cell-Material Sciences (iCeMS) in Japan have developed an advanced imaging system to identify cells responsible for storing memory within a tiny worm. Their study, published in the journal Proceedings of the National Academy of Sciences, not only offers a new way to identify molecular substrates of memory but may also one day lead to understanding how memory loss occurs in humans.

The human brain is estimated to contain approximately 100 billion cells that form trillions of connections and make up a highly complex network involved in memory. To simplify the investigation of the cells directly responsible for storing memory itself, the researchers turned to a highly defined and simple worm model, called Caenorhabditis elegans, which measures one millimeter in length and has only 302 neurons.

“Worms respond to stress from vibrations by moving backwards and escaping in a process called 'mechanosensing,’” explained Takuma Sugi, who led the study, “however, over time they get desensitized to this stimulus through memory acquisition, or learned habituation.”

Because only a few types of brain cells, known as neurons, in the worms are responsible for this process, it is possible to determine each cell’s responsibility. But to measure the worms’ movements rapidly and accurately, the scientists built a state-of-the-art integrated imaging system – involving four charge coupled device cameras, a laser, mirrors, and an automated mechanical stimulation device – to simultaneously capture the movement of 9 Petri dishes containing the genetically modified worms that emitted a green light upon laser stimulation.

“In the end, we identified two neurons, AVA and AVD interneurons that relay signals, to be responsible for the learned habituation,” said Sugi.

Since the genome of worms is 40% identical to a human’s, the scientists are hoping that the new imaging system and the interneurons they discovered may further our understanding of how memory is stored in humans.

“It is possible that these results can be applied for therapies involving memory disorders and reducing stress in the future,” said Sugi.

(Image caption: False-color image of live transgenic Caenorhabditis elegans expressing VAV-1 fused with a fluorescent protein. VAV-1 is found in a restricted number of sites in worms (pink areas), including a single neuron involved in regulating sleep)

Molecule Induces Lifesaving Sleep in Worms

Sometimes, a nematode worm just needs to take a nap. In fact, its life may depend on it. New research has identified a protein that promotes a sleep-like state in the nematode Caenorhabditis elegans. Without the snooze-inducing molecule, worms are more likely to die when confronted with stressful conditions, report researchers in the March 7, 2016 issue of the journal GENETICS.

The C. elegans sleep-like behavior is surprisingly similar to the sleep of humans and other mammals. In this state, the worm stops moving, relaxes, and uncurls its body. It also shows reduced neuronal activity and is less responsive to stimuli, but will then“wake up” if an experimenter pokes it too much. Like sleep-deprived humans, a worm that has been woken up repeatedly will fall back to sleep faster and will stay asleep longer than a well-rested worm.

The similarities are not just superficial: many of the molecules that regulate this process in C. elegans, including the epidermal growth factor receptor (EGFR), also influence sleep in mammals. This suggests that the worm sleep-like state is evolutionarily related to our own slumber. Because C. elegans is easy to experimentally manipulate and has a simple nervous system, it can serve as a tool for understanding how human sleep-wake cycles are regulated.

Worms don’t sleep on a day/night schedule like mammals. Instead, their sleep-like behavior occurs at specific stages during development; the worms enter this state each time they transition from one larval stage to another. They also sleep for several hours after a stressful event, including extremely hot or cold conditions or exposure to toxins. If they don’t get this post-stress nap, worms are less likely to survive the noxious event.

In the new research, the authors investigated whether a protein known to regulate rhythmic activities in C. elegans—like feeding, defecating, and reproducing—also regulates sleep. This protein, VAV-1, is active in a specific worm neuron that has previously been implicated in promoting sleep-like states via EGFR.

The researchers found that VAV-1 was needed specifically in the sleep-regulating neuron for sleep after stress, but not for the type of sleep linked to larval transitions. They also found that VAV-1 is needed for maintaining normal amounts of EGFR in the neuron. The sleep state could be directly induced by genetically modifying the worms so that they overproduce VAV-1.

Crucially, VAV-1 is needed for the protective effects of post-stress sleep: after being heated to a sweltering 40°C (104°F), worms lacking VAV-1 function were substantially more likely to die within the following days.

It remains unknown whether the human equivalent of VAV-1 plays a role in regulating human sleep, but the idea is worth further investigation, says study leader Kenneth Norman, of Albany Medical College. The human proteins Vav2 and Vav3 are expressed in the thalamus, a brain structure involved in regulating sleep, and, like worm VAV-1, the mammalian proteins seem to play a role in nervous system function and EGFR signaling.

“Just as in mammals, the nematode sleep program is incredibly important for life. The mystery remains what is happening during sleep that allows animals to survive,” says Norman. “We hope we can find some valuable clues by studying this evolutionarily-conserved process in a powerful model organism like C. elegans.“

Tiny worm opens big discovery on nerve degeneration

A discovery in a transparent roundworm has brought scientists one step closer to understanding nerve degeneration.

University of Queensland researchers have discovered the worm contains two proteins that play a role in the degeneration of axons in nerve cells.

Project leader Associate Professor Massimo Hilliard, from the Queensland Brain Institute, said axons – long, thread-like nerve cell sections that transmit information – were one of the first parts destroyed in neurodegenerative disease.

“By understanding the molecules involved in axonal degeneration, we can find better ways to protect neurons,” Dr Hilliard said.

“Axons are often hit and damaged by external trauma or internal injury.”

Nerve axons are also damaged in neurodegenerative conditions including Alzheimer’s, Parkinson’s and Charcot-Marie-Tooth diseases.

The researchers discovered the new proteins by using a laser to cut axons in the roundworm Caenorhabditis elegans (C. elegans), a small model system with only 302 neurons.

Monash University collaborator Dr Brent Neumann, previously of QBI, said C. elegans was an ideal research model.

“This tiny worm – about 1mm long – allows us to understand what happens in axonal degeneration on a molecular and genetic level,” Dr Neumann said.

“We found there is cross-talk between the dying neuron and the surrounding tissue, where the neuron sends a signal that it needs to be cleaned up.”

The study’s co-lead author, Ms Annika Nichols, said the discovery created new avenues for researchers seeking to limit the degenerative process.

“The aim would be to allow neurons to be better preserved,” she said.

The proteins identified seem to alter the membrane of dying neurons.

“The molecular components we discovered are conserved across evolution, meaning that the same proteins exist in the C. elegans worm as in flies, mice and humans,” Ms Nichols said.

3-D footage of nematode brains links neurons with motion and behavior

Princeton University researchers have captured among the first recordings of neural activity in nearly the entire brain of a free-moving animal. The three-dimensional recordings could provide scientists with a better understanding of how neurons coordinate action and perception in animals.

The researchers report in the journal Proceedings of the National Academy of Sciences a technique that allowed them to record 3-D footage of neural activity in the nematode Caenorhabditis elegans, a worm species 1 millimeter long with a nervous system containing a mere 302 neurons. The researchers correlated the activity of 77 neurons from the animal’s nervous system with specific behaviors, such as backward or forward motion and turning.

Much previous work related to neuron activity either focuses on small subregions of the brain or is based on observations of organisms that are unconscious or somehow limited in mobility, explained corresponding author Andrew Leifer, an associate research scholar in Princeton’s Lewis-Sigler Institute for Integrative Genomics.

“This system is exciting because it provides the most detailed picture yet of brain-wide neural activity with single-neuron resolution in the brain of an animal that is free to move around,” Leifer said.

“Neuroscience is at the beginning of a transition towards larger-scale recordings of neural activity and towards studying animals under more natural conditions,” he said. “This work helps push the field forward on both fronts.”

A current focus in neuroscience is understanding how networks of neurons coordinate to produce behavior, Leifer said. The technology to record from numerous neurons as an animal goes about its normal activities, however, has been slow to develop, he said. Neural networks are infinitesimal arrangements of chemical signals and electrical impulses that can include, as in humans, billions of cells.

The simpler nervous system of C. elegans provided the researchers with a more manageable testing ground for their instrument. Yet, it also could reveal information about how neurons work together that applies to more complex organisms, Leifer said. For instance, the researchers were surprised by the number of neurons involved in the seemingly simple act of turning around.

“One reason we were successful was that we chose to work with a very simple organism,” Leifer said. “It would be immensely more difficult to perform whole-brain recordings in humans. The technology needed to perform similar recordings in humans is many years away.  

"By studying how the brain works in a simple animal like the worm, however, we hope to gain insights into how collections of neurons work that are universal for all brains, even humans,” he said.

Leifer worked with co-first authors Jeffrey Nguyen, a postdoctoral research associate in the Lewis-Sigler Institute, and Frederick Shipley, a former research associate in the Lewis-Sigler Institute now a Ph.D. candidate in biophysics at Harvard University. The team also included Joshua Shaevitz, an associate professor of physics and the Lewis-Sigler Institute for Integrative Genomics; Ashley Linder, Mochi Liu and Sagar Setru, graduate students under Leifer and Shaevitz; and George Plummer, a former research associate at the Lewis-Sigler Institute who is now a medical student at Tufts University.

The researchers designed an instrument that captures calcium levels in brain cells as they communicate with one another. The level of calcium in each brain cell tells the researchers how active that cell is in its communication with other cells in the nervous system. The researchers induced the nemotodes’ brain cells to generate a protein known as a calcium indicator that becomes fluorescent when it comes in contact with calcium.

The researchers used a special type of microscope to record in 3-D both the nematodes’ free movements and neuron-level calcium activity for more than four minutes. Three-dimensional software the researchers designed monitored the position of an animal’s head in real time as a motorized platform automatically adjusted to keep the animal within the field of view of a series of cameras.

The entire setup drew from various disciplines and techniques, including physics, computer science and engineering, Leifer said. For instance, the real-time computer vision algorithms the researchers used to track the worms’ brains are similar in principle to the ones used in robotics or in self-driving cars.

Even more about the inner workings of the C. elegans nervous system remains to be extracted from the researchers’ data over the next year, Leifer said. The team is currently working to flesh out the correlations between neural activity and behavior in general.

“These recordings are very large and we have only begun the process of carefully mining all of the data,” Leifer said.

“An exciting next step is to use correlations in our recordings to build mathematical and computer models of how the brain functions,” he said. “We can use these models to generate hypotheses about how neural activity generates behavior. We plan to then test these hypotheses, for example, by stimulating specific neurons in an organism and observing the resulting behavior.”