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Neuroscience News Spring 2012
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Neuronal growth in a developing zebrafish, by Laura Yee, from the laboratory of Dr. Alvaro Sagasti.
Message from Chris Evans, Director of the Brain Research Institute
When Joseph Watson became the Brain Research Institute’s first Associate Director for Outreach in 2007, he was not starting a new job so much as he was receiving recognition for work he had already been doing for years. It was inevitable that someone of Joe’s energy, talent, and affability would not remain the BRI’s sole property forever. His appointment as an Associate Dean in the Graduate Division is an acknowledgement of his deep commitment to education, with which he has served the BRI and its students so well.
We congratulate Joe and wish him well in his new position, and also salute the Graduate Division for an astute choice for the job. The outreach efforts of the Brain Research Institute will continue, and in doing so we hope to build on the solid foundation that Joe established as the first Associate Director for Outreach.
Outreach has always been a part of the BRI’s mission, but Joe’s efforts in this area transformed our activities, focusing them on introducing younger students, especially those from disadvantaged schools, to the excitement of studying the brain.
The extent of Joe’s activities is difficult to describe in a limited space. Even prior to his appointment as Associate Director, he was a crucial player in the development of the Project Brainstorm (NS192B) course. He remained heavily involved in the class as a mentor, in which UCLA undergraduates develop and deliver neuroscience lessons for local K-12 students. He is also a big supporter of Interaxon, a student group with a related mandate.
His most recent project is NeuroCamp, in which Los Angeles-area high-school students come to UCLA to work in our labs to master high-level neuroscience techniques such as reading an MRI or making a DNA gel. Now in its third year, the three-week camp has provided hands-on instruction from UCLA professors to dozens of local students.
Joe has, in the five years as Associate Director for Outreach, been the friendly face of UCLA neuroscience for many aspiring young researchers. He has served as a judge at the Los Angeles Brain Bee, presented BRI Awards at the Los Angeles County and State Science Fairs, manned the Brain Research Institute’s booth at the annual alumni day, and much more.
In his new role, Joe’s commitment to teaching will be put to good use, as he will be helping to develop and implement policies to improve graduate student mentoring at UCLA. It is a good role for him, but he leaves big shoes to fill at the BRI.
|Dr. Harry Vinters.|
For a man who says that his involvement in medical history was “peripheral” to his medical interests, Dr. Harry Vinters’ recent foray into the past was fairly dramatic.
In the days following his talk at the Historical Clinicopathological Conference at the University of Maryland’s Medical School, Dr. Vinters’ findings were splashed across newspapers and cited in blog-posts the world over.
The reason? At the request of the conference organizers, the UCLA professor of neurology and neuropathology had reviewed the medical records of Vladmir Ilyich Lenin, founder of the Soviet Union. In his view, many of the circumstances of the communist leader’s death in 1924 were unusual enough that they could have been the result of poison. Vinters’ co-presenter – Russian historian Lev Lurie – said the most likely person behind such an act would have been Lenin’s successor, Josef Stalin.
Vinters had been suggested for the conference – which in previous years has re-evaluated the deaths of Edgar Allen Poe and Abraham Lincoln – for his expertise in vascular disease. He had not been familiar with much Russian history, but took to his assignment with gusto.
“When they described the exercise to me I was very intrigued by it, and very happy to get involved in the project,” he said.
Vinters was supplied with a clinical protocol that detailed Lenin’s medical history, particularly in the last two or three years of his life when the Chairman of the Council of People's Commissars was thought to have suffered a number of strokes. Vinters also had a translated copy of the autopsy report.
“I did some reading on my own, a biography of Lenin, and became quite intrigued by him as a political leader and the founder of the Soviet Union,” said Vinters.
“I was trying to get the context of this individual – a clinical history is a little bit dry. A biography fleshes out his inner circle of people that looked after him in his last days.”
According to these sources, Lenin had 4 to 5 strokes in the last two years of his life, partially losing the ability to speak after one and suffering partial paralysis after another. Eventually, he was entirely bed-ridden.
“What was striking was that he was a very young man to have that degree of vascular disease,” said Vinters. Lenin was 54 when he died, and had no known risk factors for stroke.
|Vladmir Lenin and Josef Stalin.|
Access to the Soviet leader was tightly controlled, but he did have several doctors attending to him. Lurie, the historian, believes that it is possible that one of these physicians was planted by Stalin. After all, people can recover from strokes, and Lenin always tried to give the appearance that he would recover from his illness. For Stalin, anxious for power, the temptation to hurry nature’s course might have been too great to resist.
“Lenin might have been poisoned, that will never be known,” said Vinters, adding “He probably would have died in a few weeks or months.”
Vinters did not venture any speculation as to what kind of poison might have been used, though Lurie said that Stalin backed the creation of a Cheka bureau (precursor to the KGB) for developing untraceable poisons. The series of convulsions suffered by Lenin in the hours before his death – unusual in stroke cases – are consistent with metabolic poisons.
Nearly ninety years on, there is no hope of proving the case one way or the other. Nonetheless, given the press the presentation attracted – Vinters was interviewed by media from as far away as Australia – the whiff of conspiracy will always be an attention grabber. Vinters is more philosophical.
“It’s interesting to look at disease in well known people, or historical contexts. My hypothesis was that the strokes were related to a lipid abnormality. [With modern medicines] that at least could be treated, as could his vascular disease. He could have gone on another 15 or 20 years,” said Vinters.
“For me, it is interesting because disease is really the great leveler of the playing field – no matter how famous you are, or how powerful you are, you really are at the mercy of your molecules and cells. Lenin just drew the short straw when it comes to vascular disease.”
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|Stephanie Groman, 2012 Samuel Eiduson Student Lecturer, delivered a talk entitled “Dopamine D2-Like Receptors: At the Nexus between Self Control and Addiction" on May 22nd.|
Through her studies of cognitive control and addiction, Stephanie Groman knows well the power of positive reinforcement. It is fitting that the PhD candidate has been the subject of the most positive of reinforcements the Brain Research Institute has to offer: Groman was selected to be the 2012 recipient of the Samuel Eiduson Student Lecture Award.
Groman admits to having been “completely shocked” when she was notified of the honor by BRI Associate Director for Education, Michael Levine.
“I love what I do. I think it’s a privilege to be a part of this group of neuroscientists here at UCLA, and to be giving this lecture is a huge honor. I’m very humbled,” she said.
Groman is a graduate student in the psychology department under the mentorship of Professor David Jentsch. Her graduate research focuses on cognitive control and how its underlying mechanisms pertain to addiction – particularly to methamphetamine.
“Cognitive control is the ability to use internal representations to guide future behaviors. You can imagine there’s a lot of input that we receive on a daily basis that influences what we’re going to do on the subsequent day or year,” explains Groman.
“Cognitive control” is an umbrella term that encompasses this and many related traits. Groman’s particular area of interest is inhibitory control: the ability to modify or change previously rewarding behavior when environmental factors require.
Groman explains that in the context of drug addiction, initial uses of addictive substances are very positive, with euphoric highs and, perhaps, no immediate negative effects.
“It is very rewarding, but over time it becomes detrimental to your health and your social well-being, and people are unable to stop. We think it is an impairment in inhibitory control that is making them unable to become sober and overcome a drug addiction,” she explained.
Determining the mechanism of inhibitory control and untangling its relationship with addiction has been Groman’s project for the past few years. The long-term goal is to develop pharmacological agents to help improve inhibitory control and thus provide a treatment for drug addicts.
The experiments to elucidate the nature of inhibitory control are fairly simple: animals are given three simple pictures to press (such as a green square, a purple triangle, and a yellow circle). Only one of those is reinforced with a food reward. The animals learn through trial and error how to get the snack.
In the next phase, the contingencies are changed – the purple triangle now delivers the food reward, when before it might have been the yellow circle. This requires the animal to give up a previously rewarding behavior for a new one.
How well the animals were able to adjust to these circumstances is a process called “reversal learning.” Groman found that the success of their reversal learning depended on the levels of dopamine receptors in their brains – specifically that of the D2-like receptor.
“This was the first sign that there was something specific about the D2-like receptor and inhibitory control function,” said Groman.
Many studies had already implicated the D2-like receptor to drug addiction. Nora Volkow, currently Director of the National Institute on Drug Abuse, and Dr. Edythe London, a professor in psychiatry at UCLA, demonstrated that individuals dependent upon cocaine and methamphetamine have lower D2 receptor levels in their brain than non-drug using individuals.
“We found evidence that more D2-like receptors means better reversal learning, and less D2 means worse reversal learning,” said Groman.
“Further, the density of D2-like receptors was specifically related to positive feedback – when you get a reward, there is dopamine release, and that acts on the D1 and D2 receptors. For whatever reason, the density of the D2 receptors determines how you’re going to respond to that feedback.”
D2 is distributed throughout the brain. While behaviors as complex as addiction and cognition are not constrained to one part of the brain, Groman noted that the important receptor activity within the striatum may be interacting with the orbital frontal cortex, a region of the brain important for decision-making and inhibitory control.
Groman found that animals exposed to methamphetamine not only demonstrated transient reversal-learning deficits, and reductions in D2-like receptors, but that the changes in these receptors correlated with the change in inhibitory control after drug exposure. These results indicate that drugs of abuse like methamphetamine are particularly pernicious – by down-regulating D2, they reduce the ability of the brain to learn and change behavior. This may be the mechanism by which inhibitory control deficits emerge in drug-dependent populations.
|Professor Daniel Geschwind believes that despite the disorder’s complexities, treatments for autism will continue to improve.|
Daniel Geschwind’s journey to becoming one of the world’s foremost researchers working in the field of autism was, in his telling, anything but inevitable. A series of near-chance encounters, and fortunate timing, led to a prominence in the field that has earned him, just in the past few months, induction into the prestigious Institute of Medicine of the National Academies and, closer to home, the recipient of the 2012 H.W. Magoun Lecture Award, honoring outstanding research by a BRI member.
Of course, as the saying goes, you have to be good to be lucky. Today, Geschwind is the Director of both the UCLA Center for Autism Research and Treatment (CART) and of the UCLA Neurogenetics Program and also Co-Director of the UCLA Center for Neurobehavioral Genetics Program. But in 1997, when he was a “newly hatched” academic recently arrived at UCLA, his interest lay more in brain development and neuro-asymmetry. A colleague introduced him to Portia Iverson, one of the founders of the Cure Autism Now foundation. Iverson persuaded Geschwind to serve on the foundation’s board of scientific advisers. He and his colleagues on the board – including UCLA Professors Stan Nelson and Rita Cantor – helped develop AGRE (the Autism Genetic Resource Exchange). Despite this involvement, Geschwind had intended to stay out of the field himself: “We knew we would be honest brokers… we felt that if we were using the resource a lot, it might prohibit others from using it because the others would see it as ours,” he explained.
Eventually, the temptation to enter the field to which he was already dedicating so much time became too great. He participated in a joint grant to expand the AGRE resource. That grant led to publications in the field. Those publications attracted students and other researchers looking to work with him on autism projects.
“It was a slippery slope – in a very, very positive way. All of that happenstance turned out to be one of the most fortunate things that happened in a way, because we were able to make significant contributions at the inflection point of the field when it really exploded. We happened to be in the right place at the right time.”
Until recent decades, autism has not received the depth and breadth of research and funding enjoyed by neurological disorders that have a similar prevalence in the populations (such as schizophrenia). Throughout the 60s and 70s the incidents of the disorder were often attributed to poor parenting. It only gained its own listing in the Diagnostics and Statistics Manual of Mental Disorders (DSM) in 1980. By the time Geschwind entered the field, the number of labs researching autism numbered in the dozens. Now there are hundreds, and the understanding of the disease is exploding.
One of the more significant components of that explosion included Geschwind’s discovery that the contactin associated protein-like 2 (CNTNAP2) gene was linked to some manifestations of autism. Significantly, Geschwind and his team were able to create a mouse model with a defective version of the same gene, which appears to mimic some of the behaviors typical of autism in humans. These include changes in social behavior and vocalizations. The mouse model also exhibited repetitive behaviors that respond to risperidone, a drug which is also used to treat similar symptoms in the autism spectrum disorder.
As a concrete advance, all of this sounds positive, but Geschwind cautions that the challenges of autism are considerable.
“If you take a nihilistic viewpoint, you can look at the genetics of autism and say it’s hopeless, because what the genetics have shown is that it isn’t just five or six genes that are linked to autism, but between 500 and 1000.” The Fragile X mutation accounts for the highest number of autism cases linked to a single gene, and even still these only represent one percent of all autism cases. “We’re talking about a disorder that has potentially thousands of different causes. How do you come up with a therapy for that?” asks Geschwind.
The most promising approach, in Geschwind’s view, is to identify where the genetic signals converge – targeting either molecular pathways or neural circuits. If the hundreds or thousands of potential genetic wellsprings of autism eventually flow into a few common channels, it might be possible to block or divert them further downstream, without having to address each gene individually.
“It is looking promising – I can’t tell you that there are going to be twenty different forms of autism or ten. But it is looking like there are common changes that occur in the brains of people with autism, and that’s pretty surprising,” said Geschwind.
As an MD/PhD, Geschwind is excited by the promise of such an approach, but realistic about its limits. A disorder like autism, affecting as it does social and cognitive functions, cannot be “cured” in the way that the flu might be. Social and cognitive deficits have the effect of snowballing over time – even if the underlying cause is addressed, children diagnosed with autism will still need to catch up to their peers.
“Let’s say we could cure 100 percent of the social cognition part of autism with medication. If a child is 12 years old when we give that drug to him, he’ll still have a lot of making up to do. Drugs are things that are likely to facilitate treatment, rather than cure,” said Geschwind, adding that he doesn’t foresee a treatment for autism that doesn’t have many component parts, including behavioral therapy.
While Geschwind cannot be certain what role his work will eventually play in improving the quality of life of autism patients and their families, his work with Cure Autism Now and Autism Speaks cannot help but inspire his work in the laboratory.
“Knowing people that have autism does add urgency. It’s often hard to know, in science, that what you’re doing is important – your colleagues will tell you that it is, and it might get published in big journals, but really knowing.... One of the easiest ways to measure the importance of a specific line of research is how relevant it is to a real human problem. Even if it is just baby steps, at least it’s something. I am optimistic about the future of treatments for neurologic and psychiatric diseases using targeted molecular therapy, combined with behavioral intervention.”
|Answers: 1) horseradish peroxidase 2) type 2 orexin receptorsdf|
The axons that suffuse our skin form a dense and incredibly complex pattern. But how the axons know where to grow, and how to avoid their neighbors, is not fully understood. A UCLA professor is searching for answers.
Headline Photo, Sandra Rieger
“The question we’re interested in is: how does the peripheral axon know to go to the skin, as opposed to, say, a muscle, which is innervated by a different kind of neuron, called a motor neuron? Once in the skin, how does it coordinate the placement of it’s axon territory with its neighbor?”
~ Associate Professor of Molecular, Cell, and Developmental Biology, Alvaro Sagasti
Alvaro Sagasti makes movies that, to the untrained eye, could be works of abstract art. Lines grow and branch to create intricate lattices of remarkable, yet ordered, complexity. The bright green filigrees that result trace the sensory axons of developing zebrafish.
That network is much like our own: a multitude of neurons, each projecting axons that branch throughout the skin, so that our bodies may sense pressure, heat and pain.
The resulting neural map is not just aesthetically pleasing. None of those millions of neural filaments crosses paths with one another, yet together they comprehensively innervate the skin. That property is key to their function – allowing us both to sense a stimulus and accurately determine its location on our body – but how it happens is a mystery.
“The human brain has something like a trillion connections – we only have about 50,000 genes in our genome. How can we encode such complexity? There isn’t a distinct gene that tells each neuron exactly where in the skin to send its axon. Instead there’s a set of simple instructions encoding a common strategy used by all neurons to coordinate their territories with one another," explains Sagasti, an Associate Professor of Molecular, Cell, and Developmental Biology.
Sagasti’s lab aims to unravel the nature of those instructions, and determine how axons assume their final shape, size and pattern. In practical terms, the work has important implications for human health, in that malformed axons cannot form functioning neural circuits. That is motivating, says Sagasti, but as a researcher he is energized by the sheer pleasure of trying to solve the problem.
“Basic research is fascinating and helps us understand how cells work, which in turn helps us understand disease, even if that was not the direct goal,” says Sagasti.
The cells that are of particular interest to Sagasti are called peripheral sensory neurons or somatosensory neurons.
A developing zebrafish expressing florescent proteins (Photo, Fang Wang).
“The question we’re interested in is: how does the peripheral axon know to go to the skin, as opposed to, say, a muscle, which is innervated by a different kind of neuron, called a motor neuron? Once in the skin, how does it coordinate the placement of it’s axon territory with its neighbor?”
Zebrafish are Sagasti’s means for exploring these questions. As in humans, their skin is thoroughly and evenly innervated. However, they offer advantages over mammalian models for developmental biology by virtue of being fertilized externally. Also, their bodies are nearly transparent in the early stages of development. When genetically modified to express florescent proteins, the process of axon outgrowth from a developing peripheral neuron can be observed in real time, with no invasive procedures required. Using a confocal microscope, Sagasti and his colleagues film the entire process, tracing each axon as it sprouts, grows, branches and interacts with its neighbors.
“If you watch these movies carefully, one thing you notice is that when two axons meet, they may interact with one another, but they don’t cross over each other. And this ‘repulsion’ happens when branches from two different cells, or branches from the same cell meet,” explains Sagasti.
Axons from a single neuron grow almost unchecked in a six-day old zebrafish (Photo, Alvaro Sagasti).
As an illustration of the effects of this behavior, Sagasti points to the axons from trigeminal neurons that originate on each side of a zebrafish’s head. In a normal fish, trigeminal axons from each side grow at the same rate, until each encounters the other at the midline of the head, which the axons do not cross. Sagasti believes that the axons are repelling one another, staking out their own space from which other axons are barred entry.
A simple test bore this theory out: when the trigeminal nerve from one side of the head was removed early in a fish’s development, the obverse axons extended far past the midline and into the unoccupied space.
That the axons grow into the space does not mean, however, that the signals it sends to the brain are useful. If touched on the left side of its head, a normal zebrafish will move to the right - away from the stimulus. A fish whose left-side was lacking trigeminal neurons and innervated by axons extended from the right side of the head processed a left-side touch as if coming from the right side – and thus moved towards the stimulus: “The axons were relaying information as if they were still confined to their own side of the head,” says Sagasti.
Sagasti then took the experiment to another extreme – removing all sensory neurons from the zebrafish, save one.
“That was not easy, but I did it. The question was, is there any limit to how it will grow? And the answer is, there isn’t. By day 3 it had a normal sized peripheral arbor, but it just kept growing and growing and by day seven it was huge: it took over the entire head and crossed over to the other side.”
Axons expressing a florescent protein branch out to suffuse a zebrafish’s body (Photo, Fang Wang).
A properly functioning nervous system, in which signals are accurately relayed and understood by the central nervous system, requires that this potentially runaway growth be managed and limited. Sagasti is trying to identify the molecular signals with which peripheral sensory axons inhibit one anothers’ growth. The best candidate so far was identified by fellow BRI member Larry Zipursky. He identified a molecule in fruit flies called DSCAM that appears to allow axons to recognize and avoid their own branches. Sagasti is looking for a zebrafish analogue.
Sagasti is confident of its existence, thanks to another series of experiments, performed by his graduate students Seanna Martin and Georgeann O’Brien, which tested axonal regeneration. Contrary to popular belief, nerves do have some ability to regrow after being severed, especially in the early developmental stages studied by Sagasti. He found that when a sensory axon is severed in a developing zebrafish, it does not simply grow to retrace its former route. In fact, its previously occupied pathways are a no-go zone for new axonal branches.
“They seem to specifically avoid their former territories, as if there is a ghost there that they are avoiding,” said Sagasti. This behavior may be the result of lingering repulsion signals left by the previous axon.
All of this is fascinating in its own right, but the implications for medicine are not hard to perceive: To successfully induce damaged nerves to regrow and recover normal function, it will be key that future scientists understand how axons determine their path and the signals that stop their growth.
Axons expressing a florescent protein branch out to suffuse a zebrafish’s body (Photo, Fang Wang).
Alan Robinson, Associate Vice-Chancellor, Medical Sciences and Senior Associate Dean of the David Geffen School of Medicine, chuckles at Carmine Clemente’s reminisces of arriving as a new professor at UCLA in the 1950s, as Clemente was being presented with the David Geffen School of Medicine Career Award for Excellence in Education.
Robinson introduced Clemente as “the name we all knew before we came here” and “a neuroanatomist that became a guru of total body anatomy.” Clemente was one of the earliest recruits to what became the Brain Research Institute and served as its Director from 1976 to 1987.
During the ceremony, Clemente recounted how he arrived in Los Angeles in 1953 at the invitation of BRI-founder Horace Magoun, with an offer of a professorship at UCLA’s new medical school in hand. He had driven the entire distance from Pennsylvania, but on arrival in Los Angeles was unable to find the medical school.
As Clemente recounts it, he first went to the old Veteran’s Hospital on Wilshire. He asked the woman at the information desk where the UCLA Medical Center was, only to be greeted with a baffled “The what?”
She in turn asked for help from a passing resident, who replied, “You know, I think they started a medical school over there by Bullock’s [department store].”
At this point, Clemente recalls that he started to worry: “I said to myself, ‘If a medical center has to be identified by a department store, what have I gotten into?’”
“I had traveled 3,000 miles to get here… and here was a Quonset hut across the street from Bullock’s!”
Clemente entered the corrugated metal building to meet with Magoun, who showed him his new offices. Clemente was not able to entirely mask his reaction to the unfinished state of the school, as Clemente related.
“Dr. Magoun recognized my disappointment because he took me out the back door of the Religious Conference Building and he showed me there was a great big hole in the ground and there were a few girders showing up through the concrete… and he said ‘Now, do you see that? We have got some space there!’”
"If we are literal about 'born this way,' we have to say that humans do not appear to be born with particular arousal patterns – babies aren't gay or straight."
"We used to teach in a way that demanded a tremendous amount of memorization, but now it’s more about cognitive ability and multi-tasking.”
"Did somebody do what they could to make sure this individual knew what his exposure was in terms of concussions?"
"There seems to be this sort of tipping point where patients go from having episodic headaches to having them really continuously and being in a state of constant sensory sensitivity."
The talking, hand-made brain
Brainstorm project made with duct tape, cans of Red Bull, and shoeboxes
Kevin Sweetwood, left, and Noah Lake pose with their creation
Noah Lake has made a great number of first-graders happy this year, and his landlord somewhat less happy. The recently graduated UCLA student, together with his class partner Kevin Sweetwood, is the creator of a giant model brain that has delighted and instructed elementary school children across Los Angeles.
Sweetwood and Lake were students in the Project Brainstorm course (NS192B) in which undergraduate students with an interest in neuroscience devise educational outreach projects for presentation in Los Angeles-area K-12 classrooms.
The pair decided to target early-year elementary students for their project.
“An academic presentation won’t work well for that age group, so you have to do an educational performance for them. We thought maybe we could have a brain that could talk, and then I found that Noah is really skilled at building weird stuff.”
Says Lake: “We wanted to go with the goal of having the kids learn by discovery, so I built a giant brain in my room. My landlords were ticked.”
With a mission to design and build a talking-brain puppet, Lake turned his apartment into an impromptu workshop, complete with landlord-irritating noise and fumes.
Starting with shoeboxes and duct-tape, and adding on water-bottles, Red Bull cans and fiberglas foam, Lake created an enormous model brain, complete with 500 LED lights color-coded to correspond with different lobes.
In presentations the duo performed a script largely written by Sweetwood – Lake played a doctor, and Sweetwood operated the brain-puppet. By eliciting responses from the audience, different parts of the brain are activated – loud noises light up the temporal lobe, while the frontal lobe glitters when solving a math problem.
Lake is considering building more models along the same lines for outreach purposes, with nominal resources from the BRI, but the prototype has already made an impact.
“We’re really impressed by what the kids remember afterwards – they knew at least a few lobes and their functions,” he said.
Professor Joseph Watson, who has served as the Brain Research Institute’s first Associate Director for Outreach since 2007, has been appointed the Associate Dean in the Graduate Division, effective July 1.
Watson will be relinquishing his responsibilities as Associate Director at the BRI. He points out that his new duties overlap with some of his motivating interests: the graduate division boasts its own outreach and diversity office.
“I’ll try to carry on with the same energy as I did here,” said Watson.
Watson is deeply grateful for his time at the BRI, and the resources he received for his projects.
“Great thanks to BRI Director Chris Evans for the support he gave to build the outreach program,” said Watson.
“We started out really small, and became quite big with our outreach efforts. It’s been great fun.”
One of Dr Watson’s highest profile endeavors was mentoring the Project Brainstorm (NS192) course, in which undergraduate students develop neuroscience-themed lessons for K-12 students.
Martina DeSalvo, a TA for that class, had warm words for his mentorship.
“He is great at connecting with the students and is genuinely interested in our concerns. Dr Watson is one of the few professors who will take the time to ask how you are doing and actually listen to your answer. I think he is a great choice for Associate Dean of the Graduate Division since he is so approachable and friendly,” she said.
Rafael Romero-Calderón, a lecturer in the Department of Molecular, Cell and Developmental Biology, helped design and establish the Project Brainstorm course with Dr Watson in 2006. Dr Watson was enthusiastic about the groundbreaking class, and gave it his full support.
“From the start Joe has been a pleasure to work with… Although it was a very new and experimental course, he never wavered and gave us complete freedom to develop the course,” said Romero-Calderón.
“Since then he has always been the faculty mentor for the course, 5 years running. It is fair to say that the course is what it is today in large part due to Joe’s support.”
BRI Director Chris Evans echoed that praise.
“Joe really was the heart and soul of BRI outreach for the last five years. He was brimming with energy and ideas, and there was almost no event – science fairs, Brain Bees, alumni days – where Joe wasn’t there. He was a fantastic resource for the BRI, and we wish him well in his new responsibilities.”
UCLA researchers map Phineas Gage's brain
Map is first for neuroscience’s most famous patient who suffered personality altering brain injury in 1848
By Mark Wheeler
Poor Phineas Gage. In 1848, the supervisor for the Rutland and Burlington Railroad in Vermont was using a 13-pound, 3-foot-7-inch rod to pack blasting powder into a rock when he triggered an explosion that drove the rod through his left cheek and out of the top of his head. As reported at the time, the rod was later found, "smeared with blood and brains."
Miraculously, Gage lived, becoming the most famous case in the history of neuroscience — not only because he survived a horrific accident that led to the destruction of much of his left frontal lobe but also because of the injury's reported effects on his personality and behavior, which were said to be profound. Gage went from being an affable 25-year-old to one that was fitful, irreverent and profane. His friends and acquaintances said he was "no longer Gage."
Over the years, various scientists have studied and argued about the exact location and degree of damage to Gage's cerebral cortex and the impact it had on his personality. Now, for the first time, researchers at UCLA, using brain-imaging data that was lost to science for a decade, have broadened the examination of Gage to look at the damage to the white matter "pathways" that connect various regions of the brain.
Reporting in the May 16 issue of the journal PLoS ONE, Jack Van Horn, a UCLA assistant professor of neurology, and colleagues note that while approximately 4 percent of the cerebral cortex was intersected by the rod's passage, more than 10 percent of Gage's total white matter was damaged. The passage of the tamping iron caused widespread damage to the white matter connections throughout Gage's brain, which likely was a major contributor to the behavioral changes he experienced.
Because white matter and its myelin sheath — the fatty coating around the nerve fibers that form the basic wiring of the brain — connect the billions of neurons that allow us to reason and remember, the research not only adds to the lore of Phineas Gage but may eventually lead to a better understanding of multiple brain disorders that are caused in part by similar damage to these connections.
"What we found was a significant loss of white matter connecting the left frontal regions and the rest of the brain," said Van Horn, who is a member of UCLA's Laboratory of Neuro Imaging (LONI). "We suggest that the disruption of the brain's 'network' considerably compromised it. This may have had an even greater impact on Mr. Gage than the damage to the cortex alone in terms of his purported personality change."
This is your brain on sugar: UCLA study shows high-fructose diet sabotages learning, memory
By Elaine Schmidt
Attention, college students cramming between midterms and finals: Binging on soda and sweets for as little as six weeks may make you stupid.
A new UCLA rat study is the first to show how a diet steadily high in fructose slows the brain, hampering memory and learning — and how omega-3 fatty acids can counteract the disruption. The peer-reviewed Journal of Physiology publishes the findings in its May 15 edition.
"Our findings illustrate that what you eat affects how you think," said Fernando Gomez-Pinilla, a professor of neurosurgery at the David Geffen School of Medicine at UCLA and a professor of integrative biology and physiology in the UCLA College of Letters and Science. "Eating a high-fructose diet over the long term alters your brain's ability to learn and remember information. But adding omega-3 fatty acids to your meals can help minimize the damage."
While earlier research has revealed how fructose harms the body through its role in diabetes, obesity and fatty liver, this study is the first to uncover how the sweetener influences the brain.
Scientists measure communication between stem cell-derived motor neurons, muscle cells
By Kim Irwin
UCLA researchers have developed a novel system to measure communication between stem cell–derived motor neurons and muscle cells in a Petri dish.
The study provides an important proof of principle that functional motor circuits can be created outside the body using these neurons and cells and that the level of communication between them can be accurately measured by stimulating the motor neurons with an electrode and then tracking the transfer of electrical activity into the muscle cells to which the neurons are connected. By measuring the strength of this activity, one can get a good estimation of the overall health of motor neurons.
That estimation could shed light on a variety of neurodegenerative diseases, such as spinal muscular atrophy and amyotrophic lateral sclerosis (Lou Gehrig's disease), in which communication between motor neurons and muscle cells is thought to unravel, said Bennett G. Novitch, an assistant professor of neurobiology and a scientist with the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.
The findings of the study appear May 4 in PLoS ONE, a peer-reviewed journal of the Public Library of Science.
Michele A Basso is a Professor in Residence in Psychiatry and Biobehavioral Sciences and joins the BRI from the University of Wisconsin School of Medicine and Public Health. She received her Ph.D. in behavioral neuroscience from Stony Brook University in New York. Her major area of research interest is in cognitive neuroscience and movement disorders.
“Knowing how the discharges of single neurons and groups of neurons give rise to our thoughts, feelings, decisions and choices of action lies at the fore of cognitive neuroscience. We know very little about how the activity of populations of neurons relate to behavioral choices, yet answers to such questions stand to reveal the fundamental mechanisms underlying neurological and psychiatric diseases ranging from Parkinson’s disease to addiction and schizophrenia. In my laboratory, we are exploring fundamental questions in cognitive neuroscience: 1) how are decisions represented in the sensorimotor networks of the basal ganglia and superior colliculus? 2) what are the computational principles that underlie decision-making? 3) how might these mechanisms go awry in disease? and 4) what are the cellular and synaptic mechanisms and dynamic properties of sensorimotor networks in the superior colliculus underlying decision-making?”
Andrew (Andy) C. Dean is an Assistant Professor in Residence in the Department of Psychiatry and Biobehavioral Sciences. He earned his Ph.D. from the University of Southern California. His major area of research interest is in the neuropsychology of methamphetamine dependence.
“I am a board-certified (ABPP-CN) clinical neuropsychologist, and have been investigating the neuropsychological consequences of substance abuse, particularly methamphetamine abuse, for the last 5 years. My research aims to disentangle cognitive deficits which may predispose individuals to use methamphetamine from cognitive deficits that are a consequence of methamphetamine consumption. In addition, I am the recipient of a K23 career award which aims to relate cognitive decline in methamphetamine-dependent individuals (as estimated from historical school records) to abnormalities in brain structure as assessed through structural MRI. I have published significantly on the neuropsychological function of methamphetamine-dependent individuals, and have assessed the potential benefits of cognitive-enhancing medications in this population.”
Brent Fogel is an Assistant Professor in Residence in the Department of Neurology. He earned his M.D. and Ph.D. degrees from the Medical College of Wisconsin. He studies the molecular pathogenesis of neurodegenerative and neurodevelopmental disease.
“My research is aimed at defining basic molecular mechanisms of neuronal function that can lead to neurodegenerative disorders such as spinocerebellar ataxia or neurodevelopmental conditions such as autism when disrupted. By understanding the molecular basis of these hereditary neurogenetic disorders we hope to improve current methods of diagnosis and treatment. Autistic spectrum disorders (ASDs) are severe neurodevelopmental conditions defined by variable degrees of impairment in socialization, language, and behavior which affect nearly one out of every 100 children. We are examining specific genes associated with rare forms of ASD to better identify critical molecular pathways and genetic programs in neurodevelopment whose disruption can contribute to autism. My primary clinical interest involves hereditary impairment of balance and coordination, known as ataxia. Although many genes have been identified which cause ataxia, up to 50% of families still remain unidentified. We are using genome-wide techniques, including exome sequencing, to identify novel and rare causes of genetic ataxia. We are also exploring the molecular mechanisms that cause the neurodegeneration seen in these insidiously progressive diseases.”
Peyman Golshani is an Assistant Professor in the Department of Neurology, interested in GABAergic network dysfunction in models of autism and developmental epilepsy. He earned his Ph.D. at the University of California, Davis and his M.D. at the University of California, Irvine.
“My laboratory is focused on discovering the role of different GABAergic neuronal types in the cerebral cortex and hippocampus during perception and learning in awake-behaving mice. We use in vivo two-photon calcium imaging, and in vivo whole-cell patch clamp recordings from identified interneurons and excitatory neurons in mice as they perform a perceptual learning task. We are also interested in understanding how distinct GABAergic interneuron networks malfunction in models of autism and developmental epilepsy. We are currently performing recordings in the neuroligin-3, PTEN and CNTNAP2 mutant mice, to understand how altered excitability or connectivity in cortical networks leads to abnormal network oscillations and ultimately abnormal behavior.”
Elissa Hallem is an Assistant Professor in the Department of Microbiology, Immunology, and Molecular Genetics focused on sensory neurobiology. She earned her doctorate from Yale University.
“We are interested in the function and organization of the neural circuitry that mediates odor-driven behaviors in free-living and parasitic animals. We use the free-living model nematode C. elegans as well as both insect-parasitic and mammalian-parasitic nematodes as model systems. The overall goals of our research are to understand the molecular and cellular basis of odor-driven behaviors, and to understand how olfactory systems evolve to enable species-specific behavioral repertoires. We are also interested in how parasitic nematodes use olfactory cues to locate hosts, and how the olfactory systems of parasitic animals differ from those of free-living animals.”
Sandra Loo is an Associate Professor in Residence in the Department of Psychiatry and Biobehavioral Sciences. She received her Ph.D. from the University of Hawaii in clinical psychology. She specializes in developmental neuropsychology, electrophysiology and molecular genetics.
“My research centers on the gene-brain-behavior pathways evident in childhood psychiatric disorders and translation of this work to improve treatments for these disorders. This fruitful line of research has resulted in successful funding of several federally-funded NIH grants as principal investigator (PI) and numerous collaborations where I serve as co-investigator on research projects, center grants, and pre- and post-doctoral training programs. I am the course instructor for NS240: Phenotypic Measurement of Complex Traits. This course links diverse approaches of examining phenotypic expression in genetic research to map out an integrative system of understanding the basis of complex human behavior. I also serve as training faculty for numerous post-doctoral training programs, including the Center for Neurobehavioral Genetics, Neuroimaging Training Program, and Child Mental Health Intervention Research Fellowship.”
Nader Pouratian is an Assistant Professor in the Department of Neurosurgery with particular interests in brain mapping, neuromodulation, and neural prosthetics. He completed both his medical and doctoral studies at UCLA.
“As director of the neurosurgical movement disorders program and the peripheral nerve surgery program, I specialize in surgeries to restore and preserve brain and neurological function, including deep brain stimulation for movement disorders and psychiatric disease, surgeries that require brain mapping, and peripheral nerve repairs. My research program builds upon my training in neuroimaging and signal analysis to develop restorative neurosurgical interventions and identify imaging and neurophysiological biomarkers to guide and monitor such interventions. Specific areas of research include: 1) Developing novel imaging and electrophysiological methods to personalize neuromodulatory therapies, including both fMRI, diffusion tractography based techniques, and field potential mapping; 2) Improving the accuracy and reliability of non-invasive communications systems for the neurologically impaired, including p300 speller technology; and 3) Developing EEG and ECoG based brain computer interfaces aimed at developing novel neuroprostheses to restore neurological function, including motor, visual and language function.”
The BRI is pleased to welcome its newest members.
Videographer Alex Hoang of the Department of Neurology (foreground) films Dr William Yang and students Erin Grenier (left) and Dyna Shirasaki (right) as part of a video abstract for a major paper that appeared in the July 12th edition of the journal Neuron. The paper, “Network Organization of the Huntingtin Proteomic Interactome in Mammalian Brain,” describes a system to identify proteins important to Huntington’s Disease based on the strength of their interactions with other identified Huntington’s-related proteins. It can be read on the Neuron website, while the video describing the paper can be viewed at http://bit.ly/MpZh5F
Farewell, Suzie Vader
Suzie – pictured here with Michael Levine, BRI Associate Director for Education – worked at UCLA for a remarkable 36 years, 18 of which were with the NSIDP. The program, and those who worked with her, will miss her greatly.
On June 15th the Brain Research Institute bade farewell to Graduate Neuroscience IDP Student Affairs Officer Suzie Vader. Suzie was, for hundreds of students in the Interdepartmental PhD Program for Neuroscience (NSIDP), their first contact with UCLA and a constant presence throughout their studies.
Undergraduate Neuroscience Poster SessionStudents, professors, and neuroscience enthusiasts gathered in the California NanoSystems Institute lobby for the 13th annual Neuroscience Undergraduate Poster Session. Participants browsed through 85 posters detailing the laboratory research of UCLA’s upper-year undergraduate neuroscience students. The event was held on the afternoon of May 15th.