Posts tagged fruit flies
Articles and news from the latest research reports.
Researchers Close In On The Most Important Question In Neuroscience With Fly Study
By scrutinizing the twists, turns, wiggles and squirms of 37,780 fruit fly larvae, neuroscientists have created an unprecedented view of how brain cells create behavior. The results, published March 27 in Science, draw direct connections between neurons and specific movements.
"Understanding how neural activity gives rise to behavior is the most important question in neuroscience," says neuroscientist Kay Tye of MIT, who was not involved in the research. The new study provides a way for scientists to start answering that question, she says. "I think this is a really important approach that ‘s going to be very influential."
Scientists led by Marta Zlatic of the Howard Hughes Medical Institute ‘s Janelia Farm Research Campus in Ashburn, Va., took advantage of an existing set of specially mutated flies. In each animal, small groups of neurons, usually between 2 and 15 cells, were engineered to respond to blue light. By activating handfuls of neurons with light and analyzing videos of the resulting behaviors, the researchers systematically explored most of the 10,000 neurons in Drosophila melanogaster larvae’s brain.
Vast gene-expression map yields neurological and environmental stress insights
A consortium led by scientists from the U.S. Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab) has conducted the largest survey yet of how information encoded in an animal genome is processed in different organs, stages of development, and environmental conditions. Their findings paint a new picture of how genes function in the nervous system and in response to environmental stress.
They report their research this week in the Advance Online Publication of the journal Nature.
The scientists studied the fruit fly, an important model organism in genetics research. Seventy percent of known human disease genes have closely related genes in the fly, yet the fly genome is one-thirtieth the size of ours. Previous fruit fly research has provided insights on cancer, birth defects, addictive behavior, and neurological diseases. It has also advanced our understanding of processes common to all animals such as body patterning and synaptic transmission.
In the latest scientific fruit from the fruit fly, the consortium, led by Susan Celniker of Berkeley Lab’s Life Sciences Division, generated the most comprehensive map of gene expression in any animal to date. Scientists from the University of California at Berkeley, Indiana University at Bloomington, the University of Connecticut Health Center, and several other institutions contributed to the research.
What singing fruit flies can tell us about quick decisions
You wouldn’t hear the mating song of the male fruit fly as you reached for the infested bananas in your kitchen. Yet, the neural activity behind the insect’s amorous call could help scientists understand how you made the quick decision to pull your hand back from the tiny swarm.
Male fruit flies base the pitch and tempo of their mating song on the movement and behavior of their desired female, Princeton University researchers have discovered. In the animal kingdom, lusty warblers such as birds typically have a mating song with a stereotyped pattern. A fruit fly’s song, however, is an unordered series of loud purrs and soft drones made by wing vibrations, the researchers reported in the journal Nature. A male adjusts his song in reaction to his specific environment, which in this case is the distance and speed of a female — the faster and farther away she’s moving, the louder he “sings.”
While the actors are small, the implications of these findings could be substantial for understanding rapid decision-making, explained corresponding author Mala Murthy, a Princeton assistant professor of molecular biology and the Princeton Neuroscience Institute. Fruit flies are a common model for studying the systems of more advanced beings such as humans, and have the basic components of more complex nervous systems, she said.
The researchers have provided a possible tool for studying the neural pathways behind how an organism engaged in a task adjusts its behavior to sudden changes, be it a leopard chasing a zigzagging gazelle, or a commuter navigating stop-and-go traffic, Murthy said. She and her co-authors created a model that could predict a fly’s choice of song in response to its changing environment, and identified the neural pathways involved in these decisions.
"Here we have natural courtship behavior and we have this discovery that males are using information about their sensory environment in real time to shape their song. That makes the fly system a unique model to study decision-making in a natural context," Murthy said.
"You can imagine that if a fly can integrate visual information quickly to modulate his song, the way in which it does that is probably a very basic equivalent of how a more complicated animal solves a similar problem," she said. "To figure out at the level of individual neurons how flies perform sensory-motor integration will give us insight into how a mammalian brain does it and, ultimately, maybe how a human brain does it."
Stumbling Fruit Flies Lead Scientists to Discover Gene Essential for Sensing Joint Position
Scientists at The Scripps Research Institute (TSRI) have discovered an important mechanism underlying sensory feedback that guides balance and limb movements.
The finding, which the TSRI team uncovered in fruit flies, centers on a gene and a type of nerve cell required for detection of leg-joint angles. “These cells resemble human nerve cells that innervate joints,” said team leader Professor Boaz Cook, who is an assistant professor at TSRI, “and they encode joint-angle information in the same way.”
If the findings can be fully replicated in humans, they could lead to a better understanding of, as well as treatments for, disorders arising from faulty proprioception, the detection of body position.
A report of the findings appears in the March 14, 2014 issue of the journal Science.
A Mystery of Sensation
The proprioceptive sense of how the limbs are positioned is what enables a person, even with eyes closed, to touch the tip of the nose with the tip of a finger—an ability easily impaired by alcohol, which is why traffic police often test suspected drunk drivers this way.
Scientists have known that proprioceptive signals originate from so-called mechanosensory neurons, whose nerve ends are embedded in muscles, skin and other tissues. The stretching or compression of these tissues opens ion channels in the nerve membrane, which results in a signal to the brain.
What hasn’t been clear is how such a neuron can specialize in sensing just one type of membrane-distorting stimulus—such as the angle of a limb joint—yet exclude others, such as impact pressures.
In the new study, Cook and two members of his laboratory, first author Bela S. Desai, a postdoctoral fellow, and graduate student Abhishek Chadha, sought to shed some light on this mystery with a study of Drosophila fruit flies. Quickly maturing and easily studied, Drosophila often are analyzed for clues to the genetic underpinnings of basic animal behaviors.
Following the Trail
Cook and his colleagues began with a special collection of Drosophila containing a variety of uncatalogued mutations. The scientists sifted through the collection looking for mutant flies with walking impairments and soon zeroed in on several impaired walkers that turned out to have mutations in the same gene.
The scientists named the gene stumble (stum for short) for the abnormality caused by its absence.
Using a fluorescent tracer, they then localized the expression of stum in normal flies to neurons that lay close to the three main leg joints. Each neuron’s input-sensing tendril (dendrite) grew right up to the joints—a sign that its evolved function is to detect joint angle.
The researchers also found that the protein specified by the stum gene normally migrates to the tip of each dendrite. With high-resolution microscopy, they imaged each of these tips and observed an extra length branching more or less sideways at the joint.
At ordinary, at-rest joint angles, the relative positions of the main dendrite tip and its side branch stayed more or less the same; however, at extreme joint angles, the pair stretched out. As they did, the level of calcium ions in the neuron rose sharply, suggesting that ion channels had opened and the neuron was becoming active.
Cook noted the results show how a seemingly general mechanosensory, membrane-stretch-sensitive neuron can evolve a specificity for a particular type of proprioceptive signal. “It’s a nice example of how you can create that specificity from something that only stretches mechanically,” he said.
The team is now trying to nail down the specific role of stum proteins in Drosophila and to determine whether the human version of stum—which has never been characterized—also works in joint angle sensing. Some sensory role for the human version of stum is likely, as the stum gene has been remarkably well conserved throughout animal evolution. Cook and his colleagues were even able to restore some normal walking ability to stum-mutant flies by adding the mouse version of the stum gene. “Stum is probably doing the same thing in all animals,” he said.
Researchers Identify Gene That Helps Fruit Flies Go to Sleep
A novel protein may explain how biological clocks regulate human sleep cycles
In a series of experiments sparked by fruit flies that couldn’t sleep, Johns Hopkins researchers say they have identified a mutant gene — dubbed “Wide Awake” — that sabotages how the biological clock sets the timing for sleep. The finding also led them to the protein made by a normal copy of the gene that promotes sleep early in the night and properly regulates sleep cycles.
Because genes and the proteins they code for are often highly conserved across species, the researchers suspect their discoveries — boosted by preliminary studies in mice — could lead to new treatments for people whose insomnia or off-hours work schedules keep them awake long after their heads hit the pillow.
“We know that the timing of sleep is regulated by the body’s internal biological clock, but just how this occurs has been a mystery,” says study leader Mark N. Wu, M.D., Ph.D., an assistant professor of neurology, medicine, genetic medicine and neuroscience at the Johns Hopkins University School of Medicine. “We have now found the first protein ever identified that translates timing information from the body’s circadian clock and uses it to regulate sleep.”
A report on the work was published online March 13 in the journal Neuron.
In their hunt for the molecular roots of sleep regulation, Wu and his colleagues studied thousands of fruit fly colonies, each with a different set of genetic mutations, and analyzed their sleep patterns. They found that one group of flies, with a mutation in the gene they would later call Wide Awake (or Wake for short), had trouble falling asleep at night, a malady that looked a lot like sleep-onset insomnia in humans. The investigators say Wake appears to be the messenger from the circadian clock to the brain, telling it that it’s time to shut down and sleep.
After isolating the gene, Wu’s team determined that when working properly, Wake helps shut down clock neurons of the brain that control arousal by making them more responsive to signals from the inhibitory neurotransmitter called GABA. Wake does this specifically in the early evening, thus promoting sleep at the right time. Levels of Wake cycle during the day, peaking near dusk in good sleepers.
Flies with a mutated Wake gene that couldn’t get to sleep were not getting enough GABA signal to quiet their arousal circuits at night, keeping the flies agitated.
The researchers found the same gene in every animal they studied: humans, mice, rabbits, chickens, even worms.
Importantly, when Wu’s team looked to see where Wake was located in the mouse brain, they found that it was expressed in the suprachiasmatic nucleus (SCN), the master clock in mammals. Wu says the fact that the Wake protein was expressed in high concentrations in the SCN of mice is significant.
“Sometimes we discover things in flies that have no direct relevance in higher order animals,” Wu says. “In this case, because we found the protein in a location where it likely plays a role in circadian rhythms and sleep, we are encouraged that this protein may do the same thing in mice and people.”
The hope is that someday, by manipulating Wake, possibly with a medication, shift workers, military personnel and sleep-onset insomniacs could sleep better.
“This novel pathway may be a place where we can intervene,” Wu says.
(Source: hopkinsmedicine.org)
A sparse memory is a precise memory
Particular smells can be incredibly evocative and bring back very clear, vivid memories.
Maybe you find the smell of freshly baked apple pie is forever associated with warm memories of grandma’s kitchen. Perhaps cut grass means long school holidays and endless football kickabouts. Or maybe catching the scent of certain medicines sees you revisit a bout of childhood illness.
What’s remarkable about the power of these ‘associative memories’ – connecting sensory information and past experiences – is just how precise they are. How do we and other animals attach distinct memories to the millions of possible smells we encounter?
There’s a clear advantage in doing so: accurately discriminating smells indicating dangers while making no mistakes in following those that are advantageous. But it’s a huge information processing challenge.
Researchers at Oxford University’s Centre for Neural Circuits and Behaviour have discovered that a key to forming distinct associative memories lies in how information from the senses is encoded in the brain.
Their study in fruit flies for the first time gives experimental confirmation of a theory put forward in the 1960s which suggested sensory information is encoded ‘sparsely’ in the brain.
The idea is that we have a huge population of nerve cells in many of our higher brain centres. But only a very few neurons fire in response to any particular sensation – be it smell, sound or vision. This would allow the brain to discriminate accurately between even very similar smells and sensations.
'This “sparse” coding means that neurons that respond to one odour don't overlap much with neurons that respond to other odours, which makes it easier for the brain to tell odours apart even if they are very similar,' explains Dr Andrew Lin, the lead author of the study published in Nature Neuroscience.
While previous studies have indicated that sensory information is encoded sparsely in the brain, there’s been no evidence that this arrangement is beneficial to storing distinct memories and acting on them.
'Sparse coding has been observed in the brains of other organisms, and there are compelling theoretical arguments for its importance,' says Professor Gero Miesenböck, in whose laboratory the research was performed. 'But until now it hasn’t been possible experimentally to link sparse coding with behaviour.'
In their new work, the researchers demonstrated that if they interfered with the sparse coding in fruit flies – if they ‘de-sparsened’ odour representations in the neurons that store associative memories – the flies lost the ability to form distinct memories for similar smells.
The flies are normally able to discriminate between two very similar odours, learning to avoid one and head for the other. This is controlled by the neurons that store associative memories, called Kenyon cells. There’s a separate nerve cell that acts as a control system to dampen down the activity the Kenyon cells, preventing too many of them from firing for any particular odour.
Dr Lin and colleagues showed that if this single nerve cell is blocked, the odour coding in Kenyon cells becomes less sparse and less able to discriminate between smells. The flies end up attaching the same memory to similar, yet different, odours.
Sparse coding does turn out to be important for sensory memories and our ability to act on them. Although the research was carried out in fruit flies, the scientists say sparse coding is likely to play a similar role in human memory.
Although sparse coding in the brain would seem to require much greater numbers of nerve cells, that cost appears to be worth it in being able to form distinct associative memories and act on them – thankfully. A life of experiences and memories is so much more full as a result.
Scientists wake up to causes of sleep disruption in Alzheimer’s disease
Being awake at night and dozing during the day can be a distressing early symptom of Alzheimer’s disease, but how the disease disrupts our biological clocks to cause these symptoms has remained elusive.
Now, scientists from Cambridge have discovered that in fruit flies with Alzheimer’s the biological clock is still ticking but has become uncoupled from the sleep-wake cycle it usually regulates. The findings – published in Disease Models & Mechanisms – could help develop more effective ways to improve sleep patterns in people with the disease.
People with Alzheimer’s often have poor biological rhythms, something that is a burden for both patients and their carers. Periods of sleep become shorter and more fragmented, resulting in periods of wakefulness at night and snoozing during the day. They can also become restless and agitated in the late afternoon and early evening, something known as ‘sundowning’.
Biological clocks go hand in hand with life, and are found in everything from single celled organisms to fruit flies and humans. They are vital because they allow organisms to synchronise their biology to the day-night changes in their environments.
Until now, however, it has been unclear how Alzheimer’s disrupts the biological clock. According to Dr Damian Crowther of Cambridge’s Department of Genetics, one of the study’s authors: “We wanted to know whether people with Alzheimer’s disease have a poor behavioural rhythm because they have a clock that’s stopped ticking or they have stopped responding to the clock.”
The team worked with fruit flies – a key species for studying Alzheimer’s. Evidence suggests that the A-beta peptide, a protein, is behind at least the initial stages of the disease in humans. This has been replicated in fruit flies by introducing the human gene that produces this peptide.
Taking a group of healthy flies and a group with this feature of Alzheimer’s, the researchers studied sleep-wake patterns in the flies, and how well their biological clocks were working.
They measured sleep-wake patterns by fitting a small infrared beam, similar to movement sensors in burglar alarms, to the glass tubes housing the flies. When the flies were awake and moving, they broke the beam and these breaks in the beam were counted and recorded.
To study the flies’ biological clocks, the researchers attached the protein luciferase – an enzyme that emits light – to one of the proteins that forms part of the biological clock. Levels of the protein rise and fall during the night and day, and the glowing protein provided a way of tracing the flies’ internal clock.
"This lets us see the brain glowing brighter at night and less during the day, and that’s the biological clock shown as a glowing brain. It’s beautiful to be able to study first hand in the same organism the molecular working of the clock and the corresponding behaviours," Dr Crowther said.
They found that healthy flies were active during the day and slept at night, whereas those with Alzheimer’s sleep and wake randomly. Crucially, however, the diurnal patterns of the luciferase-tagged protein were the same in both healthy and diseased flies, showing that the biological clock still ticks in flies with Alzheimer’s.
"Until now, the prevailing view was that Alzheimer’s destroyed the biological clock," said Crowther.
"What we have shown in flies with Alzheimer’s is that the clock is still ticking but is being ignored by other parts of the brain and body that govern behaviour. If we can understand this, it could help us develop new therapies to tackle sleep disturbances in people with Alzheimer’s."
Dr Simon Ridley, Head of Research at Alzheimer’s Research UK, who helped to fund the study, said: “Understanding the biology behind distressing symptoms like sleep problems is important to guide the development of new approaches to manage or treat them. This study sheds more light on the how features of Alzheimer’s can affect the molecular mechanisms controlling sleep-wake cycles in flies.
"We hope these results can guide further studies in people to ensure that progress is made for the half a million people in the UK with the disease."
Watching how the brain works
University of Miami researchers develop a method to visualize protein interactions in a living organism’s brain
There are more than a trillion cells called neurons that form a labyrinth of connections in our brains. Each of these neurons contains millions of proteins that perform different functions. Exactly how individual proteins interact to form the complex networks of the brain still remains as a mystery that is just beginning to unravel.
For the first time, a group of scientists has been able to observe intact interactions between proteins, directly in the brain of a live animal. The new live imaging approach was developed by a team of researchers at the University of Miami (UM).
(Image caption: Photonic resonance energy transfer described by Förster, or FRET, occurs when two small proteins come within a very small distance of each other — eight nanometers or less. The fluorescence lifetime of the donor molecule will become shorter — from 3 nanosecond to, perhaps, 2.5 nanoseconds. We then interpret this as evidence that the two proteins of interest are physically interacting with each other — a molecular signaling event. Credit: Akira Chiba/University of Miami)
"Our ultimate goal is to create the systematic survey of protein interactions in the brain," says Akira Chiba, professor of Biology in the College of Arts and Sciences at UM and lead investigator of the project. "Now that the genome project is complete, the next step is to understand what the proteins coded by our genes do in our body."
The new technique will allow scientists to visualize the interactions of proteins in the brain of an animal, along different points throughout its development, explains Chiba, who likens protein interactions to the way organisms associate with each other.
"We know that proteins are one billionth of a human in size. Nevertheless, proteins make networks and interact with each other, like social networking humans do," Chiba says. "The scale is very different, but it’s the same behavior happening among the basic units of a given network."
The researchers chose embryos of the fruit fly (Drosophila melanogaster) as an ideal model for the study. Because of its compact and transparent body, it is possible to visualize processes inside the Drosophila cells using a fluorescence lifetime imaging microscope (FLIM). The results of the observations are applicable to other animal brains, including the human brain.
The Drosophila embryos in the study contained a pair of fluorescent labeled proteins: a developmentally essential and ubiquitously present protein called Rho GTPase Cdc42 (cell division control protein 42), labeled with green fluorescent tag and its alleged signaling partner, the regulatory protein WASp (Wiskot-Aldrich Syndrome protein), labeled with red fluorescent tag. Together, these specialized proteins are believed to help neurons grow during brain development. The proteins were selected because the same (homolog) proteins exist in the human brain as well.
Previous methods required chemical or physical treatments that most likely disturb or even kill the cells. That made it impossible to study the protein interactions in their natural environment.
(Image caption: FRET (Förster resonance energy transfer) between the two interacting protein partners occurs, Cdc42 and WASp, within neurons, during the time and space that coincides with the formation of new synapses in the brain of the baby insect. Synapses connect individual neurons in the brain. Credit: Akira Chiba / University of Miami)
The current study addresses these challenges by using the occurrence of a phenomenon called Förster resonance energy transfer, or FRET. It occurs when two small proteins come within a very small distance of each other, (eight nanometers). The event is interpreted as the time and place where the particular protein interaction occurs within the living animal.
(Image caption: Proteins are one billionth of a human in size. Nevertheless, proteins make networks and interact with each other, like social networking humans do,” says Akira Chiba, professor of Biology in the College of Arts and Sciences at the University of Miami. “The scale is very different, but it’s the same behavior happening among the basic units of a given network.” Credit: Akira Chiba / University of Miami)
The findings show that FRET between the two interacting protein partners occurs within neurons, during the time and space that coincides with the formation of new synapses in the brain of the baby insect. Synapses connect individual neurons in the brain.
"Previous studies have demonstrated that Cdc42 and WASp can directly bind to each other in a test-tube, but this is the first direct demonstration that these two proteins are interacting within the brain," Chiba says.
(Source: eurekalert.org)
Researchers provide standardized nomenclature for the architecture of insect brains
When you’re talking about something as complex as the brain, the task isn’t any easier if the vocabulary being used is just as complex. An international collaboration of neuroscientists has not only tripled the number of identified brain structures, but created a simple lexicon to talk about them, which will be enormously helpful for future research on brain function and disease.
Nick Strausfeld and Linda Restifo, both professors in the Department of Neuroscience at the University of Arizona, worked with colleagues in Japan who led the project, and colleagues in Germany and in the UK to produce a comprehensive atlas of neuroanatomical centers and computational centers of the insect brain. In the process, the team identified many previously unknown structures. By providing the research community with a unified system of terminology, they set the stage for a systematic effort to elucidate brain structures and functions that carry over to functions of the human brain.
An article about the work appears in the scientific journal Neuron, regarded by many as one of the flagship publications of neuroscience; the online version includes an 80-page data supplement. The data will be publicly available within 6 months and include hundreds of images and 3-D video animations – amounting to an invaluable resource that will enable neuroscientists to work more efficiently, compare their results and obtain more meaningful interpretations.
"This effort provides a three-dimensional road map for describing structures for all insect brains, and enables comparisons with other arthropods," said Strausfeld, director of the UA Center for Insect Science. "It has huge value in describing network relationships between computational centers in the brain."
Scientists identify the switch that says it’s time to sleep
The switch works by regulating the activity of a handful of sleep-promoting nerve cells, or neurons, in the brain. The neurons fire when we’re tired and need sleep, and dampen down when we’re fully rested.
‘When you’re tired, these neurons in the brain shout loud and they send you to sleep,’ says Professor Gero Miesenböck of Oxford University, in whose laboratory the new research was performed.
Although the research was carried out in fruit flies, or Drosophila, the scientists say the sleep mechanism is likely to be relevant to humans.
Dr Jeffrey Donlea, one of the lead authors of the study, explains: ‘There is a similar group of neurons in a region of the human brain. These neurons are also electrically active during sleep and, like the flies’ cells, are the targets of general anaesthetics that put us to sleep. It’s therefore likely that a molecular mechanism similar to the one we have discovered in flies also operates in humans.’
The researchers say that pinpointing the sleep switch might help us identify new targets for novel drugs – potentially to improve treatments for sleep disorders.
But there is much still to find out, and further research could give insight into the big unanswered question of why we need to sleep at all, they say.
‘The big question now is to figure out what internal signal the sleep switch responds to,’ says Dr Diogo Pimentel of Oxford University, the other lead author of the study. ‘What do these sleep-promoting cells monitor while we are awake?
‘If we knew what happens in the brain during waking that requires sleep to reset, we might get closer to solving the mystery of why all animals need to sleep.’
The findings are reported in the journal Neuron. The work of the Centre for Neural Circuits and Behaviour is funded by the Wellcome Trust and the Gatsby Charitable Foundation. This study was also supported by the UK Medical Research Council, the US National Institutes of Health, and the Human Frontier Science Program.
The body uses two mechanisms to regulate sleep. One is the body clock, which attunes humans and animals to the 24 hour cycle of day and night. The other mechanism is the sleep ‘homeostat’: a device in the brain that keeps track of your waking hours and puts you to sleep when you need to reset. This mechanism represents an internal nodding off point that is separate from external factors. When it is turned off or out of use, sleep deficits build up.
What makes us go to sleep at night is probably a combination of the two mechanisms,’ says Professor Miesenböck. ‘The body clock says it’s the right time, and the sleep switch has built up pressure during a long waking day.’
The work in fruit flies allowed the critical part of the sleep switch to be discovered. ‘We discovered mutant flies that couldn’t catch up on their lost sleep after they had been kept awake all night,’ says Dr Jeffrey Donlea.
Flies stop moving when they go to sleep and require more disturbance to get them up. Sleep-deprived flies are prone to nodding off and are cognitively impaired – they have severe learning and memory deficits, much as sleep loss in humans leads to problems.
Professor Miesenböck says: ‘The sleep homeostat is similar to the thermostat in your home. A thermostat measures temperature and switches on the heating if it’s too cold. The sleep homeostat measures how long a fly has been awake and switches on a small group of specialized cells in the brain if necessary. It’s the electrical output of these nerve cells that puts the fly to sleep.’
In the mutant flies, the researchers were able to show a key molecular component of the electrical activity switch is broken and the sleep-inducing neurons are always off, causing insomnia.
(Source: ox.ac.uk)