Enigmatic Neurons Help Flies Get Oriented

Neurons deep in the fly’s brain tune in to some of the same basic visual features that neurons in bigger animals such as humans pick out in their surroundings. The new research is an important milestone toward understanding how the fly brain extracts relevant information about a visual scene to guide behavior.

As a tiny fruit fly navigates through its environment, it relies on visual landmarks to orient itself. Now, researchers at the Howard Hughes Medical Institute’s Janelia Farm Research Campus have identified neurons deep in the fly’s brain that tune in to some of the same basic visual features that neurons in bigger animals such as humans pick out in their surroundings. The new research is an important milestone toward understanding how the fly brain extracts relevant information about a visual scene to guide behavior.

In Vivek Jayaraman’s lab at Janelia, researchers are studying fly neural circuits with the goal of understanding fundamental principles of information processing. “Our hope is that over time we will get a clear picture of the neural transformations and algorithms involved in creating actions from sensory and motor information,” Vivek says. In a study published October 9, 2013, in the journal Nature, Vivek and postdoctoral researcher Johannes Seelig report on visual representations in a region of the fly brain thought to be important for visual learning.

Researchers have gathered compelling evidence that fruit flies recognize and remember visual features in their environment. Flies can use that information to seek out safe spaces or to avoid uncomfortable ones. Genetic studies have indicated that a region deep in the fly brain called the central complex is critical for these behaviors.

The central complex is found in the brains of insects and some crustaceans. “It’s not purely involved in visual learning, and is quite likely to be broadly important for sensory-motor integration in all these critters,” Vivek says, noting that in butterflies and locusts, the central complex may facilitate the use of polarized light for navigation during migration. Also, studies in cockroaches have found that it is important for turning in response to antennal touch. But in flies, no one had yet examined the activity of the neurons in the central complex to characterize their role. “It really was quite a mystery what was going on in this part of the fly brain,” Seelig says, adding that this study is only one step on a long road.

Technical limitations had prevented researchers from measuring neuronal activity in the fly’s central complex, where neurons are far smaller than they are in larger insects. Available techniques required flies to be immobilized, so scientists were limited to studying parts of the nervous system that detected sensory information, rather than those that processed that information or converted it into motor activity. But in 2010, Seelig and colleagues in Vivek’s lab at Janelia developed a method that enabled them to peer into the interior of a fly’s brain with a two-photon microscope, while the insect maintained the freedom to walk and move its wings. The microscope can detect genetically encoded proteins that light up when a nerve cell fires, due to the surge of calcium ions that accompanies a nerve impulse. “Once we had these tools, we really wanted to apply them to this central brain area,” Seelig says.

Using genetically modified strains of flies, Vivek and Seelig focused their experiments on specific classes of neurons and collected more comprehensive data about the activity of those populations than had been done in other species. They chose to zero in on a class of neurons known as ring neurons, on which the dendrites—the branching structures that connect to neighboring cells—were densely concentrated in specific spots within a region neighboring the central complex.

To test the ring neurons’ response to visual stimuli, Seelig placed the flies into a small virtual reality arena in which the flies could be presented with simple patterns of light. By monitoring the calcium-indicating dyes in the cells, Seelig could visualize nerve activity as each fly was exposed to different stimuli.

The researchers found that each neuron responded to visual stimuli in specific regions of the fly’s field of view. “Each cell seemed to have its receptive field in a slightly different area of that space,” Vivek explains. Further, they found that the orientation of the patterns that they projected onto the walls of the arena influenced the ring cells’ response: for example, vertical bars elicited a stronger response than horizontal bars for most cells.

Flies have an innate tendency to walk or fly toward vertically-oriented stimuli, but Vivek and Seelig were nonetheless surprised by the ring neurons’ strong bias towards detecting such patterns. Further, Seelig says, this preference for specific orientations parallels what others have found in larger animals. Neurons in the primary visual cortex of mammalian brains known as simple cells function similarly—identifying basic visual patterns and being tuned to their orientation. “A wide range of visual animals seem to use the same basic feature set when they break down the visual scene,” Vivek says, explaining that in humans, such simple features are combined by later brain regions into increasingly complex ones to eventually produce representations for faces.

He says it is not clear whether fruit flies reassemble the features in their visual field in the same way, or whether basic representations are instead converted directly into guidance for actions. “It’s an open question how complex a shape a fly needs to recognize and respond to,” he says.

The scientists also found that the ring neurons responded similarly to the visual environment regardless of whether the flies were stationary or walking. Flying diminished the response somewhat, but overall, Seelig says, visual patterns influenced the neurons’ activity far more than the insects’ behavior. “These particular neurons seem to filter out visual features, then send that information to other parts of the central complex that may transform that information into a behavioral signal. So this may be one of the major entry points for visual information to the region,” says Seelig.

Determining what happens next to the information received by ring neurons is an important question for Vivek and Seelig, who say they will expand their studies by testing the activity of other neurons in the central complex. “By marching through these networks, we hope to begin to understand how sensory information is integrated to make motor decisions,” Vivek explains.

Neural Simulations Hint at the Origin of Brain Waves

At EPFL’s Blue Brain facilities, computer models of individual neurons are being assembled into neural circuits that produce electrical signals akin to brain waves. The results, published in the journal Neuron, are helping solve the mystery of how and why these signals arise in the brain.

For almost a century, scientists have been studying brain waves to learn about mental health and the way we think. Yet the way billions of interconnected neurons work together to produce brain waves remains unknown. Now, scientists from EPFL’s Blue Brain Project in Switzerland, at the core of the European Human Brain Project, and the Allen Institute for Brain Science in the United States, show in the July 24th edition of the journal Neuron how a complex computer model is providing a new tool to solve the mystery.

The brain is composed of many different types of neurons, each of which carry electrical signals. Electrodes placed on the head or directly in brain tissue allow scientists to monitor the cumulative effect of this electrical activity, called electroencephalography (EEG) signals. But what is it about the structure and function of each and every neuron, and the way they network together, that give rise to these electrical signals measured in a mammalian brain?

Modeling Brain Circuitry

The Blue Brain Project is working to model a complete human brain. For the moment, Blue Brain scientists study rodent brain tissue and characterize different types of neurons to excruciating detail, recording their electrical properties, shapes, sizes, and how they connect.

To answer the question of brain-wave origin, researchers at EPFL’s Blue Brain Project and the Allen Institute joined forces with the help of the Blue Brain modeling facilities. Their work is based on a computer model of a neural circuit the likes of which have never been seen before, encompassing an unprecedented amount of detail and simulating 12,000 neurons.

“It is the first time that a model of this complexity has been used to study the underlying properties of brain waves,” says EPFL scientist Sean Hill.

In observing their model, the researchers noticed that the electrical activity swirling through the entire system was reminiscent of brain waves measured in rodents. Because the computer model uses an overwhelming amount of physical, chemical and biological data, the supercomputer simulation allows scientists to analyze brain waves at a level of detail simply unattainable with traditional monitoring of live brain tissue.

“We need a computer model because it is impossible to relate the electrical activity of potentially billions of individual neurons and the resulting brain waves at the same time,” says Hill. “Through this view, we’re able to provide an interpretation, at the single-neuron level, of brain waves that are measured when tissue is actually probed in the lab.”

Finding brain wave analogs

Neurons are somewhat like tiny batteries, needing to be charged in order to fire off an electrical impulse known as a “spike”. It is through these “spikes” that neurons communicate with each other to produce thought and perception. To “recharge” a neuron, charged particles called ions must travel through miniscule ionic channels. These channels are like gates that regulate electrical current. Ultimately, the accumulation of multiple electrical signals throughout the entire circuit of neurons produces brain waves.

The challenge for scientists in this study was to incorporate into the simulation the thousands of parameters, per neuron, that describe these electrical properties. Once they did that, they saw that the overall electrical activity in their model of 12,000 neurons was akin to observations of brain activity in rodents, hinting at the origin of brain waves.

“Our model is still incomplete, but the electrical signals produced by the computer simulation and what was actually measured in the rat brain have some striking similarities,” says Allen Institute scientist Costas Anastassiou.

Hill adds, “For the first time, we show that the complex behavior of ion channels on the branches of the neurons contributes to the shape of brain waves.”
There is still much work to be done in order to arrive at a complete simulation. While the model’s electrical signals are analogous to in vivo measurements, researchers warn that there are still many open questions as well as room to improve the model. For instance, the simulation is modeled on neurons that control the hind-limb, while in vivo data represent brain waves coming from neurons that have a similar function but control whiskers instead.

“Even so, the computer model we used allowed us to characterize, and more importantly quantify, key features of how neurons produce these signals,” says Anastassiou.

The scientists are currently studying similar brain wave phenomena in larger and more realistic neural circuits.

This computer model is drawing cellular biophysics and cognitive neuroscience closer together, in order to achieve the same goal: understanding the brain. But the two disciplines share neither the methods nor the scientific language. By simulating electrical brain activity and relating the behavior of single neurons to brain waves, the researchers aim to bridge this gap, opening the way to better tools for diagnosing mental disorders, and on a deeper level, offering a better understanding of ourselves.

Hunger affects decision making and perception of risk

Hungry people are often difficult to deal with. A good meal can affect more than our mood, it can also influence our willingness to take risks. This phenomenon is also apparent across a very diverse range of species in the animal kingdom. Experiments conducted on the fruit fly, Drosophila, by scientists at the Max Planck Institute of Neurobiology in Martinsried have shown that hunger not only modifies behaviour, but also changes pathways in the brain.

Animal behaviour is radically affected by the availability and amount of food. Studies prove that the willingness of many animals to take risks increases or declines depending on whether the animal is hungry or full. For example, a predator only hunts more dangerous prey when it is close to starvation. This behaviour has also been documented in humans in recent years: one study showed that hungry subjects took significantly more financial risks than their sated colleagues.

Also the fruit fly, Drosophila, changes its behaviour depending on its nutritional state. The animals usually perceive even low quantities of carbon dioxide to be a sign of danger and opt to take flight. However, rotting fruit and plants – the flies’ main sources of food – also release carbon dioxide. Neurobiologists in Martinsried have now discovered how the brain deals with this constant conflict in deciding between a hazardous substance and a potential food source taking advantage of the fly as a great genetic model organism for circuit neuroscience.

In various experiments, the scientists presented the flies with environments containing carbon dioxide or a mix of carbon dioxide and the smell of food. It emerged that hungry flies overcame their aversion to carbon dioxide significantly faster than fed flies – if there was a smell of food in the environment at the same time. Facing the prospect of food, hungry animals are therefore significantly more willing to take risks than sated flies. But how does the brain manage to decide between these options?

Avoiding carbon dioxide is an innate behaviour and should therefore be generated outside the mushroom body in the fly’s brain: previously, the nerve cells in the mushroom body were linked only with learning and behaviour patterns that are based on learned associations. However, when the scientists temporarily disabled these nerve cells, hungry flies no longer showed any reaction whatsoever to carbon dioxide. The behaviour of fed flies, on the other hand, remained the same: they avoided the carbon dioxide.

In further studies, the researchers identified a projection neuron which transports the carbon dioxide information to the mushroom body. This nerve cell is crucial in triggering a flight response in hungry, but not in fed animals. “In fed flies, nerve cells outside the mushroom body are enough for flies to flee from the carbon dioxide. In hungry animals, however, the nerve cells are in the mushroom body and the projection neuron, which carries the carbon dioxide information there, is essential for the flight response. If mushroom body or projection neuron activity is blocked, only hungry flies are no longer concerned about the carbon dioxide,” explains Ilona Grunwald-Kadow, who headed the study.

The results show that the innate flight response to carbon dioxide in fruit flies is controlled by two parallel neural circuits, depending on how satiated the animals are. “If the fly is hungry, it will no longer rely on the ‘direct line’ but will use brain centres to gauge internal and external signals and reach a balanced decision,” explains Grunwald-Kadow. “It is fascinating to see the extent to which metabolic processes and hunger affect the processing systems in the brain,” she adds.

Motor neurons like this one, found in the crab Cancer borealis, underlie the walking, swimming, breathing, flying and other rhythmic behaviors found in most creatures, including humans.

Eve Marder wins 2013 Gruber Neuroscience Prize

Award recognizes ‘the best neuroscience research being done anywhere’

The Gruber Foundation today awarded its 2013 neuroscience prize to Eve Marder ’69, a pioneering researcher who has dedicated her career to understanding the nervous system’s basic functions. The Victor and Gwendolyn Beinfield Professor of Neuroscience at Brandeis, Marder studies a relatively simple network of some 30 large neurons found in the gut of lobsters and crabs — a small yet elegant window into humans’ unfathomably rich nervous system, home to billions of neurons and trillions of interconnections.

The $500,000 prize recognizes and rewards “the best [neuroscience] work being done anywhere in the world,” according to the Gruber Foundation website. 

"Eve Marder has made a number of remarkable and groundbreaking discoveries that have fundamentally changed our understanding of how neural circuits operate and produce behavior," says Carol Barnes, chair of the selection advisory board to the Neuroscience Prize. "She has also been an exceptional leader outside the laboratory, working tirelessly to bring people together to improve scientific research, policy, and education."

Marder’s singular contributions to neuroscience through her use of crustaceans — in a field heavily dominated by scientists using vertebrate model organisms, chiefly rodents — have helped define how we think about neurons and their astounding capabilities. 

Despite not practicing “consensus” science — Marder avoids the well-trodden path of established modes of inquiry, such as working in vertebrates — she has received numerous accolades, including election to the National Academy of Sciences and to the helm of the Society for Neuroscience, both in 2007.

“I’m a maverick within a conservative framework — I obey carefully the rules of scientific rigor and discipline,” says Marder, who began her freshman year at Brandeis thinking she would major in politics. By her senior year, enthralled with the emerging field of neuroscience, she applied to graduate school while some of her friends made their plans to join the counterculture.

As a graduate student at the University of California, San Diego, in the early 1970s, Marder began studying the stomatogastric nervous system of the West Coast spiny lobster, Panulirus interruptus. The stomatogastric nervous system, which controls the motion of the gut, is an example of a central pattern generator. These circuits generate organized and repetitive motor patterns that also underlie walking, swimming, flying, breathing and many other rhythmic behaviors that creatures from earthworms to humans take for granted. 

The big questions Marder has asked throughout her career attempt to understand the fundamental nature of neuronal circuit operation. In a Brandeis lab staffed by post-docs, graduate students and undergraduates, she’s helped advance basic tenets of neuroscience while continuing to refine several related lines of inquiry. 

Early in Marder’s Brandeis career, her lab demonstrated that neuromodulatory substances such as dopamine, serotonin and neuropeptides can alter circuit performance so that the same group of neurons can produce a variety of behaviors. Her research has helped reshape the way scientists think about conditions like depression, now believed to stem from imbalances in neuromodulation. 

Later, her lab studied how neurons and networks maintain stable network performance despite the ongoing turnover of the membrane proteins that give neurons their characteristic electrical properties. Most recently, her lab is studying animal-to-animal variability in neuronal properties. How much variability in circuit function is there between animals even as they respond similarly to changes in hormones or temperature?

“I’m always looking for the things we can study more effectively than someone working in a large nervous system,” explains Marder. “I don’t want to work on problems that someone else can do better.”

Awarded by a distinguished panel of experts following an international nomination process, the Gruber Foundation neuroscience prize is a humbling honor, Marder says. It is also recognition that great science requires both intellectual risk-taking and persistence. 

Marder plans to celebrate, just not over a fancy lobster dinner. She gave up eating crustaceans long ago.

Researchers Discover How Brain Circuits Can Become Miswired During Development

Researchers at Weill Cornell Medical College have uncovered a mechanism that guides the exquisite wiring of neural circuits in a developing brain — gaining unprecedented insight into the faulty circuits that may lead to brain disorders ranging from autism to mental retardation.

In the journal Cell, the researchers describe, for the first time, that faulty wiring occurs when RNA molecules embedded in a growing axon are not degraded after they give instructions that help steer the nerve cell. So, for example, the signal that tells the axon to turn — which should disappear after the turn is made — remains active, interfering with new signals meant to guide the axon in other directions.

The scientists say that there may be a way to use this new knowledge to fix the circuits.

"Understanding the basis of brain miswiring can help scientists come up with new therapies and strategies to correct the problem," says the study’s senior author, Dr. Samie Jaffrey, a professor in the Department of Pharmacology.

"The brain is quite ‘plastic’ and changeable in the very young, and if we know why circuits are miswired, it may be possible to correct those pathways, allowing the brain to build new, functional wiring," he says.

Disorders associated with faulty neuronal circuits include epilepsy, autism, schizophrenia, mental retardation and spasticity and movement disorders, among others.

In their study, the scientists describe a process of brain wiring that is much more dynamic than was previously known — and thus more prone to error.

Proteins Sense the Environment to Steer the Axon

During brain development, neurons have to connect to each other, which they do by extending their long axons to touch one another. Ultimately, these neurons form a circuit between the brain and the target tissue through which chemical and electrical signals are relayed. In this study, researchers investigated neurons that travel up the spinal cord into the brain. “It is very critical that axons are precisely positioned in the spinal cord,” Dr. Jaffrey says. “If they are improperly positioned, they will form the wrong connections, which can lead to signals being sent to the wrong target cells in the brain.”

The way that an axon guides and finds its proper target is through so-called growth cones located at the tips of axons. “These growth cones have the ability to sense the environment, determine where the targets are and navigate toward them. The question has always been — how do they know how to do this? Where do the instructions come from that tell them how to find their proper target?” Dr. Jaffrey says. The team found that RNA molecules embedded in the growth cone are responsible for instructing the axon to move left or right, up or down. These RNAs are translated in growth cones to produce antenna-like proteins that steer the axon like a self-guided missile.

"As a circuit is being built, RNAs in the neuron’s growth cones are mostly silent. We found that specific RNAs are only read at precise stages in order to produce the right protein needed to steer the axon at the right time. After the protein is produced, we saw that the RNA instruction is degraded and disappears," he says.

"If these RNAs do not disappear when they should, the axon does not position itself properly — it may go right instead of left — and the wiring will be incorrect and the circuit may be faulty," Dr. Jaffrey says.

RNAs have Tremendous Power over Brain Development

The research finding answers a long-standing puzzle in the quest to understand brain wiring, says Dr. Dilek Colak, a postdoctoral associate in Dr. Jaffrey’s laboratory.

"There have been a series of discoveries over the last five years showing that proteins that control RNA degradation are very important for brain development and, when they are mutated, you can have spasticity or other movement disorders," Dr. Colak says. "That has raised a major question — why would RNA degradation pathways be so critical for properly creating brain circuits?

"What we show here is that not only does RNA need to be present in growth cones to give instructions, it then also needs to be removed from the growth cones to take away those instructions at the right time," she says. "Both those processes are critical and it may explain why there are so many different brain disorders associated with ineffective RNA regulation."

"The idea that control of brain wiring is located in these RNA molecules that are constantly being dynamically turned over is something that we didn’t anticipate," Dr. Jaffrey adds. "This tells us that regulating these RNA degradation pathways could have a tremendous impact on brain development. Now we know where to look to tease apart this process when it goes awry, and to think about how we can repair it."

(Image: Chad Baker)

Scientists Discover Molecule Triggers Sensation of Itch

Scientists at the National Institutes of Health report they have discovered in mouse studies that a small molecule released in the spinal cord triggers a process that is later experienced in the brain as the sensation of itch.

The small molecule, called natriuretic polypeptide b (Nppb), streams ahead and selectively plugs into a specific nerve cell in the spinal cord, which sends the signal onward through the central nervous system. When Nppb or its nerve cell was removed, mice stopped scratching at a broad array of itch-inducing substances. The signal wasn’t going through.

Because the nervous systems of mice and humans are similar, the scientists say a comparable biocircuit for itch likely is present in people. If correct, this start switch would provide a natural place to look for unique molecules that can be targeted with drugs to turn off the sensation more efficiently in the millions of people with chronic itch conditions, such eczema and psoriasis.

The paper, published online in the journal Science, also helps to solve a lingering scientific issue. “Our work shows that itch, once thought to be a low-level form of pain, is a distinct sensation that is uniquely hardwired into the nervous system with the biochemical equivalent of its own dedicated land line to the brain,” said Mark Hoon, Ph.D., the senior author on the paper and a scientist at the National Institute of Dental and Craniofacial Research, part of the National Institutes of Health.

Hoon said his group’s findings began with searching for the signaling components on a class of nerve cells, or neurons, that contain a molecule called TRPV1. These neurons, with their long nerve fibers extending into the skin, muscle, and other tissues, help to monitor a range of external conditions, from extreme temperature changes to detecting pain.

Yet little is known about how these neurons recognize the various sensory inputs and, like sorting mail, know how to route them correctly to the appropriate pathway to the brain.

To fill in more of the details, Hoon said his laboratory identified in mice some of the main neurotransmitters that TRPV1 neurons produce. A neurotransmitter is a small molecule that neurons selectively release when stimulated, like a quick pulse of water from a faucet, to communicate sensory signals to other nerve cells.

The scientists screened the various neurotransmitters, including Nppb, to see which ones corresponded with transmitting sensation.

“We tested Nppb for its possible role in various sensations without success,” said Santosh Mishra, lead author on the study and a researcher in the Hoon laboratory. “When we exposed the Nppb-deficient mice to several itch-inducing substances, it was amazing to watch. Nothing happened. The mice wouldn’t scratch.”

Further experiments established that Nppb was essential to initiate the sensation of itch, known clinically as pruritus. Equally significant, the molecule was necessary to respond to a broad spectrum of pruritic substances. Previous research had suggested that a common start switch for itch would be unlikely, given the myriad proteins and cell types that seemed to be involved in processing the sensation.

Hoon and Mishra turned to the dorsal horn, a junction point in the spine where sensory signals from the body’s periphery are routed onward to the brain. Within this nexus of nerve connections, they looked for cells that expressed the receptor to receive the incoming Nppb molecules.

“The receptors were exactly in the right place in the dorsal horn,” said Hoon, the receptor being the long-recognized protein Npra. “We went further and removed the Npra neurons from the spinal cord. We wanted to see if their removal would short-circuit the itch, and it did.”

Hoon said this experiment added another key piece of information. Removing the receptor neurons had no impact on other sensory sensations, such as temperature, pain, and touch. This told them that the connection forms a dedicated biocircuit to the brain that conveys the sensation of itch.

But the scientists had stepped into a conundrum. Previous reports had suggested that another neurotransmitter called GRP might initiate itch. If that wasn’t the case, where did GRP fit into the process?

They tested the receptor neurons that express GRP, finding the previous reports were correct about this molecule relaying the signal to the central nervous system. GRP just enters the picture after Nppb already has set the sensation in motion.

Based on these findings, Nppb would seem to be an obvious first target to control itch. But that’s not necessarily the case. Nppb also is used in the heart, kidneys, and other parts of the body, so attempts to control the neurotransmitter in the spine has the potential to cause unwanted side effects.

“The larger scientific point remains,” said Hoon. “We have defined in the mouse the primary itch-initiating neurons and figured out the first three steps in the pruritic pathway. Now the challenge is to find similar biocircuitry in people, evaluate what’s there, and identify unique molecules that can be targeted to turn off chronic itch without causing unwanted side effects. So, this is a start, not a finish.”

(Image: GETTY)

Scientists develop worm EEG to test the effects of drugs

Scientists from the University of Southampton have developed a device which records the brain activity of worms to help test the effects of drugs.

NeuroChip is a microfluidic electrophysiological device, which can trap the microscopic worm Caenorhadbitis elegans and record the activity of discrete neural circuits in its ‘brain’ - a worm equivalent of the EEG.

C. elegans have been enormously important in providing insight into fundamental signalling processes in the nervous system and this device opens the way for a new analysis. Prior to this development, electrophysiological recordings that resolve the activity of excitatory and inhibitory nerve cells in the nervous system of the worm required a high level of technical expertise - single microscopic (1mm long) worms have to be trapped on the end of a glass tube, a microelectrode, in order to make the recording. The worms are very mobile as well as being small and this can be a challenging procedure.

The microfluidic invention consists of a reservoir through which worms can be fed, one after the other, into a narrow fluid-filled channel. The channel tapers at one end and this captures the worm by the front end. The worm is then in the correct orientation for recording the activity of the nervous system in the anterior of its body. The device incorporates metal electrodes, which are connected to an amplifier to make the recording. The design of the trapping channel has been optimised by PhD student Chunxiao Hu, so that the quality of the worm ‘EEG’ recording is sufficient to resolve the activity of components of the neural circuit in the worm’s nervous system.

This device has been used to detect the effects of drugs and is highly suitable for high throughput screens (which allow researchers to quickly conduct millions of chemical, genetic or pharmacological tests) in neurotoxicology and for generic screening for neuroactive drugs. It has more power to resolve discrete effects on excitatory, inhibitory or modulatory transmission than previously possible with behavioural screens.

Lindy Holden-Dye, Professor of Neuroscience at the University of Southampton and lead author of the paper, says: “We are particularly interested in using this as a sensitive new tool for screening compounds for neurotoxicity. It will allow us to precisely quantify sub-lethal effects on neural network activity. It can also provide an information rich platform by reporting the effects of compounds on a diverse array of neurotransmitter pathways, which are implicated in mammalian toxicology. “

The research, which is published in the latest issue of the journal PLOS One, is a joint project between the University’s Centre for Biological Sciences and the Hybrid Biodevices Group.

Bach to the blues, our emotions match music to colors

Whether we’re listening to Bach or the blues, our brains are wired to make music-color connections depending on how the melodies make us feel, according to new research from the University of California, Berkeley. For instance, Mozart’s jaunty Flute Concerto No. 1 in G major is most often associated with bright yellow and orange, whereas his dour Requiem in D minor is more likely to be linked to dark, bluish gray.

Moreover, people in both the United States and Mexico linked the same pieces of classical orchestral music with the same colors. This suggests that humans share a common emotional palette – when it comes to music and color – that appears to be intuitive and can cross cultural barriers, UC Berkeley researchers said.

“The results were remarkably strong and consistent across individuals and cultures and clearly pointed to the powerful role that emotions play in how the human brain maps from hearing music to seeing colors,” said UC Berkeley vision scientist Stephen Palmer, lead author of a paper published this week in the journal Proceedings of the National Academy of Sciences.

Using a 37-color palette, the UC Berkeley study found that people tend to pair faster-paced music in a major key with lighter, more vivid, yellow colors, whereas slower-paced music in a minor key is more likely to be teamed up with darker, grayer, bluer colors.

“Surprisingly, we can predict with 95 percent accuracy how happy or sad the colors people pick will be based on how happy or sad the music is that they are listening to,” said Palmer, who will present these and related findings at the International Association of Colour conference at the University of Newcastle in the U.K. on July 8.  At the conference, a color light show will accompany a performance by the Northern Sinfonia orchestra to demonstrate “the patterns aroused by music and color converging on the neural circuits that register emotion,” he said.

The findings may have implications for creative therapies, advertising and even music player gadgetry. For example, they could be used to create more emotionally engaging electronic music visualizers, computer software that generates animated imagery synchronized to the music being played. Right now, the colors and patterns appear to be randomly generated and do not take emotion into account, researchers said.

They may also provide insight into synesthesia, a neurological condition in which the stimulation of one perceptual pathway, such as hearing music, leads to automatic, involuntary experiences in a different perceptual pathway, such as seeing colors.  An example of sound-to-color synesthesia was portrayed in the 2009 movie The Soloist when cellist Nathaniel Ayers experiences a mesmerizing interplay of swirling colors while listening to the Los Angeles symphony. Artists such as Wassily Kandinksky and Paul Klee may have used music-to-color synesthesia in their creative endeavors.

Nearly 100 men and women participated in the UC Berkeley music-color study, of which half resided in the San Francisco Bay Area and the other half in Guadalajara, Mexico. In three experiments, they listened to 18 classical music pieces by composers Johann Sebastian Bach, Wolfgang Amadeus Mozart and Johannes Brahms that varied in tempo (slow, medium, fast) and in major versus minor keys.

In the first experiment, participants were asked to pick five of the 37 colors that best matched the music to which they were listening. The palette consisted of vivid, light, medium, and dark shades of red, orange, yellow, green, yellow-green, green, blue-green, blue, and purple.

Participants consistently picked bright, vivid, warm colors to go with upbeat music and dark, dull, cool colors to match the more tearful or somber pieces. Separately, they rated each piece of music on a scale of happy to sad, strong to weak, lively to dreary and angry to calm.  

Two subsequent experiments studying music-to-face and face-to-color associations supported the researchers’ hypothesis that “common emotions are responsible for music-to-color associations,” said Karen Schloss, a postdoctoral researchers at UC Berkeley and co-author of the paper. 

For example, the same pattern occurred when participants chose the facial expressions that “went best” with the music selections, Schloss said. Upbeat music in major keys was consistently paired with happy-looking faces while subdued music in minor keys was paired with sad-looking faces. Similarly, happy faces were paired with yellow and other bright colors and angry faces with dark red hues.

Next, Palmer and his research team plan to study participants in Turkey where traditional music employs a wider range of scales than just major and minor. “We know that in Mexico and the U.S. the responses are very similar,” he said. “But we don’t yet know about China or Turkey.”

Restoring paretic hand function via an artificial neural connection bridging spinal cord injury

Functional loss of limb control in individuals with spinal cord injury or stroke can be caused by interruption of the neural pathways between brain and spinal cord, although the neural circuits located above and below the lesion remain functional. An artificial neural connection that bridges the lost pathway and connects brain to spinal circuits has potential to ameliorate the functional loss. Yukio Nishimura, Associate Professor of the National Institute for Physiological Sciences, Japan, and Eberhard Fetz, Professor and Steve Perlmuter, Research Associate Professor at the University of Washington, United States investigated the effects of introducing a novel artificial neural connection which bridged a spinal cord lesion in a paretic monkey. This allowed the monkey to electrically stimulate the spinal cord through volitionally controlled brain activity and thereby to restore volitional control of the paretic hand. This study demonstrates that artificial neural connections can compensate for interrupted descending pathways and promote volitional control of upper limb movement after damage of neural pathways such as spinal cord injury or stroke. The study will be published online in Frontiers in Neural Circuits on April 11.

"The important point is that individuals who are paralyzed want to be able to move their own bodies by their own will. This study was different from what other research groups have done up to now; we didn’t use any prosthetic limbs like robotic arms to replace the original arm. What’s new is that we have been able to use this artificial neuronal connection bypassing the lesion site to restore volitional control of the subject’s own paretic arm. I think that for lesions of the corticospinal pathway this might even have a better chance of becoming a real prosthetic treatment rather than the sort of robotic devices that have been developed recently", Associate professor Nishimura said.