Guest Post By Sheena Faherty, graduate student in Biology
How do our neurons discriminate between a punch to the face or a kiss on the cheek? Between something potentially harmful, and something pleasant?
A new study published this week in Current Biology offers an answer by describing a previously uncharacterized gene required for pain sensing.
This work comes out of Dan Tracey’s lab at the Duke Institute for Brain Sciences. They named the gene balboa in honor of fictional prizefighter Rocky Balboa and his iconic immunity to pain.
Float like a drosophila, sting like a …oh, never mind.
The researchers found that the balboa gene is only active in pain-sensing neurons and is required for detection of painful touch responses. Without it, neurons can’t distinguish between something harmful and something pleasant.
Does the ultimate prize of naming of the gene inspire any boxing matches between lab mates?
“In the fly community, we are allowed to have these creative gene names, so discussions about the decision on naming are more fun than argumentative,” Tracey says.
Tracey’s lab is concerned with sensory neurobiology, the study of how neurons transform cues from the surrounding environment to signals that can be interpreted by the brain. Ultimately, the lab group hopes to identify the underlying molecular mechanisms that are involved in our sense of touch.
Pugilistic fly artwork designed by Jason Wu, a neurobiology graduate student in Jorg Grandl’s lab
“It’s unclear what happens during that moment of touch sensation when sensory neurons detect and convert a touch stimulus into a nerve impulse,” said graduate student Stephanie Mauthner, who is the lead author on the Rocky paper. “It’s also ambiguous how nerves are capable of discriminating the threshold of touch intensity.”
Although the fruit fly has a relatively simple central nervous system, Tracey’s group uses it as model because it has many of the same neural circuits that the human brain has.
“[Our goal was to figure out] what molecular components are required for pain neurons to detect harsh touch responses and what is the mechanism for performing this task,” Mauthner said.
Using fluorescent cells, their study also shows that balboa interacts with another protein of the same family named pickpocket. They’re hopeful that this gene duo can be a potential target for pain medications that could discriminate between different sites of pain throughout the body.
Pain relievers such as aspirin or ibuprofen work broadly throughout the whole body—with no discrimination to where the pain is actually occurring. But, by working towards the exact molecular mechanism of pain signaling, genes like balboa and pickpocket are potential candidates for more targeted therapeutics.
Grad student Stephanie Mauthner hangs out with one of her many vials of flies (courtesy of Stephanie Mauthner)
CITATION: “Balboa Binds to Pickpocket In Vivo and Is Required for Mechanical Nociception in Drosophila Larvae,” Stephanie E. Mauthner, Richard Y. Hwang, Amanda H. Lewis, Qi Xiao, Asako Tsubouchi, Yu Wang, Ken Honjo, J.H. Pate Skene, Jörg Grandl, W. Daniel Tracey Jr. Current Biology, Dec. 15, 2014. DOI: http://dx.doi.org/10.1016/j.cub.2014.10.038
A handful of bird species survived the K-T extinction. Chicken genomes have changed the least since that terrible day.
By Karl Leif Bates
In the beginning was the Chicken. Or something quite like it.
At that moment 66 million years ago when an asteroid impact caused the devastating Cretaceous–Tertiary (K-T) extinction, a handful of bird-like dinosaur species somehow managed to survive.
The cataclysm and its ensuing climate change wiped out much of Earth’s life and brought the dinosaurs’ 160-million-year reign to an end.
But this week, the genomes of modern birds are telling us that a few resourceful survivors somehow scratched out a living, reproduced (of course), and put forth heirs that evolved to adapt into all the ecological niches left vacant by the mass extinction. From that close call, birds blossomed into the more than 10,000 spectacularly diverse species we know today.
Erich Jarvis
Not all birds are descended from chickens, but it’s true that chicken genes have diverged the least from the dinosaur ancestors, says Erich Jarvis, an associate professor of neurobiology in the Duke Medical School and Howard Hughes Medical Institute Investigator.
He’s one of the leaders on a gigantic release of scientific data and papers that tells the story of the plucky K-T survivors and their descendants, redrawing many parts of the bird family tree.
From giant, flightless ostriches to tiny, miraculous hummingbirds, the descendants of those proto-birds now rule over the skies, the forests, the cliff-faces and prairies and even under water. While other birds were learning to reproduce songs and sounds, hover to drink nectar, dive on prey at 230 miles per hour, run across the land at 40 miles per hour, migrate from pole to pole or spend months at sea out of sight of land, the chickens just abided, apparently.
Sweet little chickadees had a very big, very scary cousin. “Parrots and songbirds and hawks and eagles had a common ancestor that was an apex predator,” Erich Jarvis says. “We think it was related to these giant ‘terror birds’ that lived in the South American continent millions of years ago.”
The new analyses released this week are based on complete-genome sequencing done mostly at BGI (formerly Beijing Genomics Institute). and DNA samples prepared mostly at Duke. The budgerigar, a parrot, was sequenced at Duke. There are 29 papers in this first release, but many more will tumble out for years to come.
“In the past, people have been using 1, 2, up to 20 genes, to try to infer species relationships over the last 100 million years or so,” Jarvis says. But whole-genome analysis drew a somewhat different tree and yielded important new insights.
More than 200 researchers at 80 institutions dove into this sea of big data like so many cormorants and pelicans, coming up with new insights about how flight developed and was lost several times, how penguins learned to be cold and wet and fly underwater and how color vision and bright plumage co-evolved.
The birds’ genomes were found to be pared down to eliminate repetitive sequences of DNA, but yet to still hold microchromosomal structures that link them to the dinosaurs and crocodiles.
The sequencing of still more birds continues apace as the Jarvis lab at Duke does most of the sample preparation to turn specimens of bird flesh into purified DNA for whole-genome sequencing at BGI. (More after the movie!)
As one of three ring-leaders for this massive effort, Erich Jarvis is on 20 papers in this first set of findings. Eight of those concern the development of song learning and speech, but the other ones are pretty cool too:
Evidence for a single loss of mineralized teeth in the common avian ancestor. Robert W. Meredith, et al.Science. Instead of teeth, modern birds have a horny beak to grab and a muscular gizzard to “chew” their food. This analysis shows birds lost the use of five genes related to making enamel and dentin just once about 116 million years ago.
Complex evolutionary trajectories of sex chromosomes across bird taxa. Qi Zhou, et al. Science. The chromosomes that determine sex in birds, the W and the Z, have a very complex history and more active genes than had been expected. They may hold the secret to why some birds have wildly different male and female forms.
Three crocodilians genomes reveal ancestral patterns of evolution among archosaurs. Richard E Green, et al Science. Three members of the crocodile lineage were sequenced revealing ‘an exceptionally slow rate of genome evolution’ and a reconstruction of a partial genome of the common ancestor to all crocs, birds, and dinosaurs.
Evidence for GC-biased gene conversion as a driver of between-lineage differences in avian base composition. Claudia C. Weber, et al, Genome Biology. The substitution of the DNA basepairs G and C was found to be higher in the genomes of birds with large populations and shorter generations, confirming a theoretical prediction that GC content is affected by life history of a species.
Low frequency of paleoviral infiltration across the avian phylogeny.Jie Cui, et al. Genome Biology. Genomes maintain a partial record of the viruses an organism’s family has encountered through history. The researchers found that birds don’t hold as much of these leftover bits of viral genes as other animals. They conclude birds are either less susceptible to viral infection, or better at purging viral genes.
Genomic signatures of near-extinction and rebirth of the Crested Ibis and other endangered bird species. Shengbin Li, et al Genome Biology. Genomes of several bird species that are recovering from near-extinction show clues to the susceptibilities to climate change, agrochemicals and overhunting that put them in peril. This effort has created better information for improving conservation and breeding these species back to health.
Dynamic evolution of the alpha (α) and beta (β) keratins has accompanied integument diversification and the adaptation of birds into novel lifestyles. Matthew J. Greenwold, et al. BMC Evolutionary Biology. Keratin, the structural protein that makes hair, fingernails and skin in mammals, also makes feathers. Beta-keratin genes have undergone widespread evolution to account for the many forms of feathers and claws among birds.
Comparative genomics reveals molecular features unique to the songbird lineage. Morgan Wirthlin, et al. BMC Genomics. Analysis of 48 complete bird genomes and 4 non-bird genomes identified 10 genes unique to the songbirds, which account for almost half of bird species today. Two of the genes are more active in the vocal learning centers of the songbird brain.
Reconstruction of gross avian genome structure, organization and evolution suggests that the chicken lineage most closely resembles the dinosaur avian ancestor. Michael N. Romanov, et al. BMC Biology. Of 21 bird species analyzed, the chicken lineage appears to have undergone the fewest changes compared to the dinosaur ancestor.
Two Antarctic penguin genomes reveal insights into their evolutionary history and molecular changes related to the cold aquatic environment. Cai Li, et al. Gigascience. The first penguins appeared 60 million years ago during a period of global warming. Comparisons of two Antarctic species show differences and commonalities in gene adaptations for extreme cold and underwater swimming.
Evolutionary genomics and adaptive evolution of the hedgehog gene family (SHH, IHH, and DHH) in vertebrates. Joana Pereira, et al. PLoS ONE. Whole-genome sequences for 45 bird species and 3 non-bird species allow a more detailed tracing of the evolutionary history of three genes important to embryo development.
A Duke lab led the effort to isolate bird DNA for sequencing at BGI: (L-R) Erich Jarvis, associate professor of neurobiology and Howard Hughes Medical Institute investigator, lab research analyst Carole Parent, undergraduate research assistant Nisarg Dabhi, and research scientist Jason Howard. (Duke Photo, Les Todd)
Walking’s healthier than driving, if you look both ways. (Karin Beate Nøsterud, norden.org via wikimedia commons)
Walking as you go to school, shopping or work is good for your health and it saves money and carbon emissions. But the way American cities are built, some of the folks who would benefit most from a little bipedalism live in the areas that make walking the hardest.
That’s the upshot of a complete analysis of the nation’s “built environment,” by a pair of researchers from Duke and the University of Michigan.
Katherine King, a visiting assistant professor in Community and Family Medicine at Duke, worked with Philippa Clarke, an associate research professor in epidemiology at U-M, to examine more than 63,000 census tracts in 48 states and the District of Columbia from the 2000 census.
They used linear regression analysis to look for relationships between five neighborhood characteristics (income, education, race/ethnic composition, age distribution and gender) and five factors that contribute to “walkability,” such as the presence of intersections and building density.
The poorest neighborhoods, and those with the highest education levels — downtown areas of cities –were found to be the most walkable. But census tracts with a higher proportion of children and older adults, the suburbs, were apparently less walkable, with fewer intersections and lower density of street segments.
The authors suggest that urban planners — make that SUB-urban planners — should give careful thought to the health implications of the living spaces they’re designing. King’s work was supported by the US EPA’s environmental public health division.
Citation – A Disadvantaged Advantage in Walkability: Findings From Socioeconomic and Geographical Analysis of National Built Environment Data in the United States Katherine King and Philippa Clarke. American Journal of Epidemiology, Online Nov. 19, 2014.
You wouldn’t know it from the war drums banging over at ESPN this week in advance of Thursday night’s football showdown, or the hairy eyeball the frat boys give you for wearing the wrong shirt in Chapel Hill, but our two fine institutions, Duke and UNC-Chapel Hill, are actually very good friends and close collaborators. …At the faculty level, at least.
It’s quite common for a major research paper coming out of either campus to include collaborators from the other Tier 1 research university just 10 miles away. It only makes sense. When the ARRA Stimulus funding was on the table a few years ago, the two pulled together on all sorts of projects to bring about $400 million in federal tax dollars back to the Triangle.
And now, a new program announced just a few weeks ago will actually pay researchers from both schools to be friends! Can you imagine?
A Chapel Hill taunt. (Not actually supported by the data, but whatever.)
Duke’s Translational Medicine Institute (DTMI) and the North Carolina Translational and Clinical Sciences Institute (NC TraCS) are awarding $50,000 grants to research projects that are trying to speed laboratory medical findings into the clinic or the population. (That’s what “translation” means.) The only catch is that the application has to include one co-investigator from each school.
“I think that although we come from different ends of Tobacco Road and our different shades of blue compete passionately in sports, when it comes to translating medical progress and health care to the community, we can be very collaborative,” Jennifer Li of the Duke Translational Medicine Institute told the DTMI newsletter.
Just look at those long faces! Poor kids. A Duke buzzer-beater will do that to you.
Naturally, the newsletter then had to quote a Tarheel: “On a scientific basis, collaborative teams are formed based on shared interests and complimentary resources, skills and experiences,” said John Buse, deputy director of the NC Translational and Clinical Sciences Institute. “The hope (is) that the sum is greater than the parts.”
Perhaps, Dr. Buse, perhaps. But what’s the fun in that?
Duke Forest director Sara Childs, left, got into the trees a ways with some of the annual gathering guests.
The map that Kelly Oten showed at the Duke Forest annual gathering Thursday night could have been a metaphor for the 7,000-acre research and teaching forest itself .
Her map showed the entire state with Duke Forest in the middle, and advancing legions of forest-killing pests approaching from all sides. In this case, Oten, a forest health monitoring coordinator for the North Carolina Forest Service, was talking about bugs that kill native trees in various horrible ways.
But it might just as well have been a map of encroaching development, rapacious deer, unleashed, freely pooping dogs or any of the dozens of other things that threaten to change the face of this forested oasis on a daily basis.
In a two-hour meeting with snacks and wine, forest director Sara Childs, her staff and Oten brought a room full of forest-lovers up to date on the current health of Duke’s forested reserve and the status of all kinds of invasive species. Things are going well, said Childs, who took over this year after the retirement of Judd Edeburn, but the challenges never go away.
Childs said the forest hosted 84 research projects from 23 institutions in the last year. More than 500 students attended class activities — probably a dramatic undercount — and 827 person-hours went into the ambitious overhaul of the heavily used trails and bridges in the Korstian Division.
The biggest blow of the year was the back-to-back ice storms in February and March that disturbed 187 acres in all, 22 of which simply had to be salvage-cut because they were beyond repair, Childs said.
Deer management seems to be helping, Childs said. Ideally, they’d like to see 15-20 of the giant herbivores per square mile, but the count was more like 80 per mile when they started fall culling operations five years ago. The cull is on right now, by the way, closing the Durham, Korstian and Blackwood Divisions Monday through Friday. That’s in effect until Dec. 19, so stay safely away.
Sara Childs presents Judd Edeburn with the plaque for a new division named in his honor. He doesn’t get to keep it; it’ll be bolted to a very big rock.
At the end of the evening, Childs and the Duke Forest staff showed Edeburn a handsome new brass plaque that will be installed at the entrance to the former Eno division to rename that section of the forest in his honor.
Guest Post by Ken Kingery, Pratt School of Engineering
If you think ordering a drink from Starbucks can be a tall order, try picking out the right material for a new product or experiment. An iced, half-caff, four-pump, sugar-free, venti cinnamon dolce soy skinny latte may be a mouthful, but there are hundreds of thousands of known—and unknown—compounds to choose from, each with their own set of characteristics.
Screenshot of the AFLOW library search interface. The software combs through four giant databases of chemical compounds.
For example, take the family of materials Bi2Sr2Can-1CunO2n+4+x, or bismuth strontium calcium copper oxide for short, if you can call it that. These compounds have the potential to change the world because of their ability to become superconducting at relatively high temperatures. But each sibling, cousin or distant relative has its own physical variations…so how to choose which to pursue?
Thanks to Stefano Curtarolo and his research group, now there’s an app for that.
Curtarolo leads a collection of research groups from seven universities specializing in something they call materials genomics. The group—called the AFLOW consortium—uses supercomputers to comb databases for similar structures and builds theoretical models atom-by-atom to predict how they might behave.
With help from several members of the consortium, Pratt School of Engineering postdocs Cormac Toher, Jose Javier Plata Ramos and Frisco Rose, along with Duke student Harvey Shi, have spent the past few months building a system that combs through four materials databases. Users can choose the elements and characteristics they want a material to have—or not to have—and the website will play matchmaker.
Want a two-element compound containing either silicon or germanium—but not gallium—that is stable enough to withstand high temperatures? Not a problem. How about an electric insulator made from transition metals with a certain crystal structure? AFLOW has you covered.
Stefano Curtarolo is a professor of mechanical engineering and materials science at Duke
One of the four databases searched by the program draws from an international collection of compounds with structures known from experimentation. The other three contain single- double- or triple-element compounds, and are not limited to previously explored materials. Through their molecule-building algorithms, the AFLOW consortium is constantly adding prospective materials to these four libraries.
The search engine currently can sort through more than 622,000 known and unknown compounds, and more than 1,000 new ones are added each week. Curtarolo, a professor of materials science and physics, hopes that the open-source program will continue to grow in materials and searchable characteristics to help scientists connect to their ideal material. To see how it works for yourself, take it for a test drive here.
As for an equivalent database of coffee drinks, that has yet to be built. So if you’re looking through AFLOW for a hot, lactose-free drink featuring 150 to 200 mg of caffeine and less than 200 calories made with beans from South America, you’re out of luck.
Grad school can seem like walking down a well-lit path in an otherwise dark forest. It’s easy to see the academic path, but who knows what might happen if you step off of it? (Illustration: Ted Stanek)
Guest post from Ted Stanek, PhD candidate in neurobiology
The Duke Institute for Brain Sciences’ Beyond Academia panel on Oct. 30 tried to illuminate the many career paths available to PhDs and spread hope rather than dread in the minds of Triangle area graduate students.
There has been a flood of articles recently about the increase in competition in the academic world for tenure-track faculty positions and federal funding. They all harped on the perils of staying in academia and the tragedy of being a PhD student or postdoc in such a climate.
Many of these stories focus on the terrifying choice that all PhDs and postdocs face at various points in their career: whether or not they want to stay on the academic track. The alternative feels like jumping off of a cliff, and many people complain that programs which accept more PhD students than there are academic jobs available are effectively pushing students towards that cliff.
Ted Stanek is a PhD student in neurobiology.
In the face of this negative outlook for PhDs, the Duke Institute for Brain Sciences recently provided welcome insight into the variety of non-academic careers that may lie in a PhD’s future. Beyond Academia was a day-long workshop consisting of five groups of 3-4 panelists discussing their own career trajectories, what their careers are like, and how they prepared to achieve such positions. Each panelist had a neuroscience or biomedical science PhD, and each had found a successful and fulfilling career outside of the academic niche.
“There are no ‘alternative careers’,” Katja Brose, Senior Editor of Neuron, emphasized in her keynote address. “There are just careers.”
Workshop panelists revealed just how many careers were available to PhDs. A major point reinforced during the event was that you are never “stuck” on the academic track. You have the option of changing careers every step of the way – even after you’ve reached the level of tenured faculty.
Switching career paths, however, is a daunting task – a common reason why many PhD students go straight into a postdoc. It’s easy to see how the skills that you learn as a graduate student will transfer to skills you can use as a postdoc, and then as a young faculty.
Elizabeth Brannon, a professor of psychology & neuroscience who organized the seminar, pointed out in her welcoming speech that PhD students have limited access to professionals outside of academia, making it difficult to even identify non-academic careers that may interest them, let alone prepare for them.
While many of these careers beyond academia do require some type of preparation, this preparation may simply consist of pursuing your interests while completing your PhD. Writing or editing for your lab, starting up a journal club, and participating in university or professional organizations are all great ways to boost your resume and develop your interests.
Perhaps the hardest part of preparing for any career, academic or otherwise, is undergoing that initial period of self-reflection necessary to identify what skills you possess in your current position, what interests you about your job, and how your life values might impact your career.
“The point at which your skills, interests, and values overlap determines your career sweet spot,” Brose said.
Do you especially enjoy the administrative aspects of academia? Maybe grant management is the way to go. How about actually conducting experiments to discover new biological mechanisms? Perhaps working in a pre-clinical lab for a pharmaceutical company is the place for you. What if you love writing – either the spinning of a story (science writer/freelancer), or writing down the scientific facts with precise and accurate language (medical writer)? Are you interested in new biological technology (intellectual property and patent law)? Or helping to change laws about science (science policy)? Maybe you just love reading papers and debating where they should be published (journal editor).
All of these positions highly value PhDs in particular, no matter what the specifics of your thesis are. Every PhD in the brain and behavioral sciences, whether molecular, systems, or behavioral, develops what career advisors call transferable skills. These highly valued “super powers” as one panelist put it, include being able to communicate technical topics to a diverse audience, working with team members, learning a large amount of information quickly and effectively, being resilient in the face of unexpected adversity, and thinking critically to solve complex problems. The overwhelming message from Beyond Academia was that no matter where you end up, after you get your PhD you can find a career that will make you happy and fulfilled.
To me, it seems like pursuing a PhD is a lot like walking down a well-lit path in an otherwise dark forest. It’s easy to see the next step along the path to academia, but who knows what might happen if you step off of it?
Thanks to Beyond Academia, that forest is now a little brighter.
The NIH’s mapping initiative called BRAIN has been likened to a moon shot.
By Kelly Rae Chi
The federal government’s BRAIN Initiative to chart the neural connections in the human brain and explain how its diverse and ever-changing cells make us who we are has been compared to landing a person on the moon.
Last summer the National Institutes of Health (NIH) described its vision as a 100-plus-item list of deliverables, proposed budgets and milestones. Last week, the NIH awarded the first round of seed money toward those goals — $46 million — some it for Duke scientists.
And this week, Gregory Farber, director of the National Institute of Mental Health’s Office of Technology Development and Coordination, visited Duke to talk about the timeline for the decade-long initiative.
Duke scientists in the audience peppered him with questions about how he sees it evolving.
“What I learned in Greg Farber’s talk is that the BRAIN Initiative offers a serious –and I mean serious — ten-year plan to catalyze game-changing discoveries in understanding the human brain, and in doing so, provide new treatments for disorders, like Alzheimer’s disease, that can rob us of our very humanity,” said Michael Platt, director of the Duke Institute for Brain Sciences.
BRAIN stands for ‘Brain Research through Advancing Innovative Neurotechnologies.’ It’s all about technology, and it will cost a pretty penny for its public and private partners. Fiscal Year 2014’s $46 will develop a “parts list” for the brain and probe neural circuitry in a variety of ways. And that’s only the start.
The initiative is expected to begin in earnest in 2016, take five years for tool development and five more to apply those tools to study humans wherever possible.
“We have a strong sense that we want to see these tools have clinical applications in the not-too-distant future, but I’m being careful not to define ‘not-too-distant’,” Farber told a room full of neuroscientists, many of them working on human brain imaging.
Allen Song is a professor of Radiology, Neurobiology, Psychiatry and Biomedical Engineering.
In the audience was Allen Song, professor and director of the Duke-UNC Brain Imaging Analysis Center and among the first scientists awarded NIH BRAIN funds. He is leading a team that will further develop and validate a human brain imaging technique dubbed ‘NEMO,’ for Neuro-Electro-Magnetic Oscillations.
The hope is that NEMO, and other ‘next-generation’ brain imaging advances supported with the initiative, will help solve some of the limitations of today’s technologies. Functional magnetic resonance imaging (fMRI), for example, measures changes in the levels of oxygenated blood in the brain. It’s an indirect way of seeing neural activity, and it comes with a several-second delay.
Used with traditional MRI scanners, NEMO will more directly tune into neurons, which naturally create waves of electrical activity in the brain at specific frequencies.
For example, “if this technology works, we can tune our machine to listen to the 10-Hertz oscillation in the brain as a result of neuron firing,” Song said. Then, by driving neurons into specific oscillations at different times and during different tasks, the scientists may be able to resolve the brain in better spatial and temporal detail.
Song said that although he’s excited and confident, he already feels the pressure of a tight timeline for the project. It won’t be possible to finish it in the three-year timeframe. Even with continued funding, at the end of 12 years, “we don’t know where we will be,” he said.
Still, Song and his colleagues were all smiles as they filed in for Farber’s talk. “It’s a thrill to see Allen Song and his colleagues win support in the first round of BRAIN grants to develop the next generation in human brain imaging technology,” Platt said. “I’m confident Duke neuroscience will figure prominently in the BRAIN Initiative, given our focus on interdisciplinary innovation and collaboration.”
No actual cartoon fish will be used in the NEMO project.
Duke brain scientists are shaking up their field’s understanding of a part of the brain called the basal ganglia that’s sort of a crossroads for many important functions.
A simplified map of the pathways dopamine (blue) and serotonin travel to the basal ganglia, the snail-shaped structure in the middle of the human brain.
Basal ganglia signaling is involved in movement, learning, language, attention, and motivation. But this centrality also makes it challenging to figure out how it works, said Henry Yin, an assistant professor of psychology and neuroscience at Duke, and a member of the Duke Institute for Brain Sciences.
As healthy mice collected food pellets delivered into a cup once per minute every minute for two hours. Yin’s team was recording the electrical activity of neurons projecting to and from the basal ganglia.
Henry Yin is an assistant professor in Psychology and Neuroscience.
Naturally, the mice picked up food less often as they became full and some of the cells that use dopamine to signal reward showed less activity.
But other dopamine cells became more active.
In a paper describing these experiments , Yin’s group proposed that the cells’ activity reflected not reward but what the animals are physically doing.
This was new and Yin became curious. Was there a direct relationship between movement and dopamine activity?
Using a different experimental setup with cameras and pressure pads, Yin’s group quantified mouse movements while recording neural activity. “What happens is that whenever there’s movement, (there are phases of) dopamine activity,” Yin said to a room full of fellow neuroscientists during a recent seminar at Duke.
Putting the mice on top of a “shaker,” a piece of lab equipment normally used to gently shake tubes and dishes full of liquids, they found individual dopamine neurons responded to specific directions the mouse was tilted on the shaker. The same was true for nearby neurons that signal using GABA, an inhibitory chemical in the brain.
Using additional methods for tracking motions of freely moving mice, the group has discovered specific sub-populations of neurons that respond to different aspects of movement, especially movement speed and acceleration.
The researchers have also created transgenic mice whose dopamine neurons can be stimulated using light. Turning on these neurons makes the mice move.
Yin is working on publishing these results, but he said there’s a lot of resistance in the field. His work appears to be directly challenging the dogma that dopamine is linked to reward. He says it might actually be involved in generating movements.
“Let’s say you’re drinking coffee and that’s a reward,” Yin said. “I record your neural activity, and it’s correlated with coffee. You might say it’s a coffee neuron. But that’s not true unless you can measure the movement kinematics and rule out other possible correlations. What we’re seeing is that, with no exceptions, the phasic activity of DA neurons is always correlated with movement.”
Yin’s work also challenges theories about why people with Parkinson’s disease, whose dopamine cells degenerate, often have trouble initiating movement, or they move more slowly than they mean to.
“If you’re a doctor, a neurologist, what you study is the rate model. That’s the textbook description,” Yin said. The gist of the rate model is that the basal ganglia is constantly putting the “brakes” on behavior, and when its neurons settle down, that allows for movement. Parkinson’s patients can’t initiate movements, it’s thought, because their basal ganglia output (more specifically, the rate of firing in the inhibitory output neurons) is too high, producing excessive braking.
In contrast, according to Yin’s work, at least four different types of basal ganglia output neurons are adjusting behavior dynamically and continuously, to shape the speed and direction of movement.
When the activity of these neurons is constant, it reflects a stable posture, Yin said. So he argues that the problem with Parkinson’s patients is not that their basal ganglia output is too high, but that this output is stuck in firing mode. The downstream brain areas required for postural control don’t get the right commands.
Nicole Calakos is an associate professor of neurology.
“Henry’s studies are really exciting because we’ve thought about this circuitry in one way for a very long time and his findings really cast a new light on those interpretations,” said Nicole Calakos, M.D., Ph.D., an associate professor of neurology. “I treat patients with Parkinson’s disease and other diseases that involve this circuitry. It is interesting to consider this alternate view to explain the problems my patients face in doing their day-to-day activities.”
Calakos’ own research focuses on how learning alters signal processing by the basal ganglia, and how the signaling goes awry in brain diseases such as obsessive-compulsive disorder. Duke researchers are finding compelling links between different behavioral states and specific long-lasting patterns of activity in the basal ganglia.
Jennifer Groh, a professor of psychology and neuroscience at Duke, is launching a Coursera course next week and a book next month — both devoted to the topic of the 2014 Nobel Prize in Physiology or Medicine which was awarded Monday.
This year’s Nobel went to three scientists who discovered the neurons responsible for our brain’s form of GPS, crucial for our ability to navigate a complex and changing world. And that’s the topic of Groh’s work, “Making Space: How the Brain Knows Where Things Are.”
The cover of Jennifer Groh’s new book.
In 1971, John O´Keefe of University College London had shown that certain neurons in the hippocampus — a brain area known for its role in memory — are active only when a rat is in certain spot in its environment. O’Keefe called these neurons ‘place cells.’
In 2005, May-Britt Moser and Edvard Moser, partners in both marriage and science at the Norwegian University of Science & Technology in Trondheim, described a region near the hippocampus in which cells became activated in a unique grid-like pattern as an animal moved through its environment. They dubbed them ‘grid cells.’
“O’Keefe and the Mosers made a discovery that I find endlessly fascinating — that a brain network closely tied with memory is extremely sensitive to one’s location in space,” Duke’s Groh said. “This suggests that our movements through the world play a role in helping us remember.”
Jennifer Groh is a professor of Psychology and Neuroscience.
“Once you know this, you see the implications everywhere,” said Groh who is also a member of the Duke Institute for Brain Sciences. “For example, when you go to a college reunion and are roaming your old haunts, long dormant memories come flooding back.”
Groh’s new book, Making Space: How the Brain Knows Where Things Are, explains more about how our brains convey a sense of location and direction. In it, Groh makes the case that such spatial processing is inextricably tied to our ability to think and remember.
Her openly available Coursera course based on the book, “The Brain and Space,” starts Monday, October 13. To celebrate the Mosers and O’Keefe winning the prize, she made her lecture on the place cells available on YouTube.
