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A publication of the Brain Research Institute University of California, Los Angeles Volume 22, Issue 2. Spring/Summer 2014 MODELING HUMAN BEHAVIOR invertebrate insights miracle mice & more

MODELING HUMAN BEHAVIOR invertebrate insights miracle mice

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Page 1: MODELING HUMAN BEHAVIOR invertebrate insights miracle mice

A publication of the Brain Research Institute

University of California, Los AngelesVolume 22, Issue 2. Spring/Summer 2014

MODELING HUMAN BEHAVIORinvertebrate insights

miracle mice & more

Page 2: MODELING HUMAN BEHAVIOR invertebrate insights miracle mice

CO

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INSIDE THIS ISSUE

PAGE TITLE

MODEL BEHAVIOR 2 Part 1 -- Insights from invertebrates 5 Part 2 -- William Yang and the mouse 7 Part 3 -- Sex differences in animal models

FEATURED EVENTS 8 The Eiduson Student Lecture The HW Magoun Lectureship

NEW MEMBERS10 Pamela Kennedy Andrew Fuligni11 Rajesh Kumar Benjamin Ellingson12 Gregory Miller Samantha Butler Alapakkam Sampath

AWARDS & ACKNOWLEDGEMENTS13 David Jentsch & Dario Ringach THE BIOMEDICAL RESEARCH LEADERSHIP AWARD Reggie Edgerton and Daniel Lu NIBIB AWARD Lara Ray RESEARCH SOCIETY ON ALCOHOLISM YOUNG INVESTIGATOR AWARD14 Ira Kurtz DONALD T. STERLING FOUNDATION GIFT Jesse Rissman FACULTY CAREER DEVELOPMENT AWARD Gary Small PRESIDENT-ELECT OF THE AMERICAN ASSOCIATION FOR GERIATRIC PSYCHIATRY Michele Basso, Peyman Golshani, Jason Hinman, Felix Schweizer BRI/INTEGRATIVE CENTER FOR NEURAL REPAIR/CTSI RESEARCH AWARDS

NEXT GENERATION NEUROSCIENTISTS15 Brain Awareness Week Los Angeles Brain Bee California State Science Fair16 Empow-Her STEM Day

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Summer 2014 approaches. With it comes a season of change in the leadership of the Brain Research Institute. I am pleased to announce that Felix Schweizer and Tom O’Dell will take the reins of the Interdepartmental Graduate Program in Neuroscience (NSIDP) as Chair and Co-Chair respectively. Felix, a Professor and Vice Chair for Education in Neurobiology, is an exceptional researcher. His insights into the molecular mechanisms through which neurons communicate are at the forefront of investigations into one of the “big” questions facing neuroscience. Likewise, Tom O’Dell, Professor and Interim Chair of Physiology, investigates these mechanisms in context of learning and memory formation. In addition, Baljit Khakh, Executive Vice Chair of Physiology and Professor of Physiology and Neurobiology, has been appointed as our Associate Director for Research. The importance of his work in interrogating astrocytes, particularly in context of neurological and psychiatric disorders, was acknowledged less than a year ago, when the NIH granted him one of 12 Pioneer Awards. Bal, Felix and Tom are equally well known for their strong commitment to education and mentorship, a key function of the BRI. They will be building from the solid foundation created by Mike Levine, the previous Chair of the NSIDP, and David Jentsch, the former Associate Director for Research. I cannot thank Mike and David enough for their contributions -- and both will continue to be valued and prominent members of BRI faculty. In fact, Mike, in his capacity as Associate Director for Education, is now tasked with the mission to create an Education Office facilitating pre- and postdoctoral training associated with T32s.

Summer also brings a wave of research accomplishments that have garnered international attention. It is great to see the recognition Reggie Edgerton’s breakthrough treatment for spinal cord injury is receiving. Hundreds of mainstream press outlets all over the world are paying attention. Other BRI faculty are affecting basic and clinical science practice at the policy level. I was gratified to hear Rhonda Voskuhl on NPR’s Morning Edition, as she eloquently explained the significance of the estrogen hormone, estriol, in alleviating symptoms of multiple sclerosis (MS) in women. Rhonda’s most recent clinical study observed a decrease in MS relapses in 47% of her subjects. In the interview, she characterized this as “quite remarkable”. I would characterize this as a major step towards a successful clinical intervention that will stop MS in its tracks. Her work also points to the significance of sex differences in neuroscience research, as has Art Arnold’s studies into sex differences in obesity. Both have been a major force in prompting the NIH to mandate that preclinical research study both male and female models. Historically, male models have dominated neuroscience research. I believe the new NIH policy will lead to widespread insights in a number of diseases, likely some as radical as Rhonda’s.

Scientific breakthroughs are hardly overnight occurrences. They are usually the result of career trajectories characterized by a steadfast dedication in the face of what may seemingly be insurmountable challenges. The BRI is currently working to cut through a similarly challenging problem in the culture of the neuroscientific community -- the gender imbalance in the makeup of our students, researchers, and faculty. At present, 51% of undergraduates at UCLA in Science, Technology, Engineering, Mathematics (STEM) fields (including psychology) are female. The graduate student statistics decrease to 30% female and as one proceeds up the tenure ladder, female participation drops even more dramatically. I believe the gender gap will eventually close, but it’s important to keep reaching out to K-12 female students and young women who might not consider neuroscience as a viable option. This is why we support programs like Martina DeSalvo’s inaugural “Empow-Her STEMday”, and why the event was oversubscribed with volunteers and participants. We are pleased to be part of this mission. The female faculty and students within the BRI, NSIDP, and undergraduate community provide a very good place to start.

Wishing you all the best for the summer ahead, Chris

A MESSAG

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Front cover: Upper: Fission defect in C. elegans. Mitochondrial outer membrane (green), matrix (red) in a worm muscle cell. The matrix is swollen, the outer membrane fails to divide. Image by Alexander van der BliekLower: GFP driven by the Islet-3 promoter in transgenic zebrafish larva at 78 hours post fertilization. The transgene labels all sensory neurons. Image by Sandra Rieger from the laboratory of Alvaro Sagasti.

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2 Neuroscience News 22(2)

MODELING behaviormissives from the forefront of experimental models at UCLA

- I -INSIGHTS FROM INVERTEBRATES

In many ways, the fact that neuroscience research is predicated on animal models seems counter-intuitive. After all, what can a worm actually have in common with a human being? Why is the memory of a sea slug remotely relevant to the intricacies of mammalian brains? Who can possibly benefit from studying the startle reflex of a fish? And how can the twitching of fly wings provide any insight into human behavior?

It is only during the last hundred years that neuroscience has progressed from a field reliant on philosophical and anatomical precepts, to a level capable of uncovering structures hidden from the naked human eye. Revolutionary advances in biotechnology have given neuro-disciplines a lens to the invisible, followed by new capacities to target and manipulate biological content. The result has been exponential increases in understanding the genetic, neuronal, and chemical functions and dysfunctions of the human organism.

Many of these mechanisms are common across species. Some of them have existed since the Cambrian explosion 542 million years ago. In fact, ancient organisms may be key to understanding human brain functions, because fundamental properties that enable survival are maintained across millenia. Mechanisms that are conserved over the course of evolution are important.

Evolution doesn’t get rid of things that work.

One of the species that crawled out of the Cambrian primordial ooze is the worm; more specifically the roundworm Caenorhabditis elegans (C. elegans). These transparent, tiny hermaphrodites lack circulation and respiration, yet these deficits serve to enhance the power of the C. elegans animal model. Simplicity. Alexander van der Bliek, PhD, is a Professor of Biological Chemistry. Dr. van der Bliek first started working with worms as a postdoctoral student in the 1990’s. “My first exposure to C. elegans came about because I was investigating the role of dynamin, a gene that, when mutated, causes paralysis,” he recalls. Not much work had been done on dynamin in worms at the time. “It was good to switch to such a simple, clear system.”

In fact, this worm is the only multi-cellular organism to have its connectome completely mapped out. With a total of 302 neurons in every C. elegans, research has a clarity that is impossible to duplicate in other organisms. This simplicity does not undercut the applicability of the worm model to mammals, Dr. van der Bliek says. “Usually, what we find in worms is equally applicable in mammalian cells. The homologies of basic processes translate, so neuronal functions are pretty much the same.”

Dr. van der Bliek’s research focuses on the fission and fusion processes of mitochondria -- the double-membrane-bound subcellular organelles that facilitate metabolic functions. “Mitochondrial division is much clearer in worms than in human cells. We can see fission defects, or problems in the outer membrane.” Fission is essential both in the formation of new mitochondria and removal of damaged mitochondria. “When fission is disrupted, damaged portions of mitochondria can poison the cell.”

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Spring/Summer 2014 3

At present, mitochondrial fission and fusion proteins have clear relationships both with blindness by causing optic nerve degeneration and with Charcot-Marie-Tooth disease (CMT), one of the most common inherited neurological diseases. CMT affects approximately 1 in 2,500 people, and is characterized by such symptoms as muscle weakness and decreased muscle size.

CMT mechanisms also provide insight to other major neurological diseases. The same fission- and fusion-inducing proteins active in Charcot-Marie-Tooth disease may be linked to the pathways of Parkinson’s disease. These proteins may even be at work in Alzheimer’s disease. In fact, Dr. van der Bliek says, after over a decade of work exploring mitochondrial fission, fusion and stress in the worm, “the implications in terms of human diseases keep broadening. The fission-fusion process causes a lot of problems. We don’t have to look very far to find disease connections. The diseases come to us.”

C. elegans has also been instrumental in the development of now ubiquitous genetic engineering technologies. Neuroscientists used the organism to develop RNA interference (RNAi), which allows reverse genetic engineering in the organism. This allows the functional study of a gene that begins with the genetic sequence rather than a mutant phenotype. In the case of the worm, in less than 24 hours RNAi can create a knockdown gene function without changing its DNA.

The BRI’s 25th Annual Poster Session Lecture was presented Dr. Martin Chalfie, the Novel Laureate who co-developed green fluorescent protein (GFP) in C. elegans. (For more information, see Neuroscience News Fall 2013.) In doing so, Dr. Chalfie and the worm gave researchers an invaluable tool to report gene expression in a variety of organisms, ranging from zebrafish to mammalian cells.

A fruit fly suspended in an electronic “virtual reality” flight simulator that allows analysis of motion in response to appetitive food odors and visual clues. Image by Scott Chandler from a study by Dawnis Chow in the laboratory of Mark Frye.

A developing zebrafish expressing fluorescent proteins. Image by Fang

Microtubules and actin structure in Aplysia sensory-motor neuron. Fluorescent protein Dendra-tagged tubulin (green) was overexpressed in Sensory neuron with F-Actin staining(red). Image by Sangmok Kim from the laboratory of Kelsey Martin.

Right: C. elegans express fluorescent

proteins.

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“We are likely to understand the behavior of C. elegans on a cellular and molecular level, before any other organism”....

So says David Glanzman, PhD, Professor of Integrative Biology & Physiology, and Neurobiology. Dr. Glanzman studies both Aplysia (or sea slug) and zebrafish. His primary interest is gaining insight into way memories are maintained. Dr. Glanzman started as a psychology graduate student at a time “that was characterized by the belief that we didn’t need to understand the brain to understand the mind,” he says. He quickly transitioned to neuroscience, with a particular focus on electrophysiological investigation of the rabbit cortex. In the course of these studies, though, he gradually became convinced that simpler models were better equipped to provide insight into the brain. “Since C. elegans aren’t amenable to electrophysiological techniques, I decided to investigate the sea slug.”

Like the worm, Aplysia is relatively simple, with an estimated 20,000 central nervous system neurons. These neurons are immense and, as one of the largest somatic cells in the animal kingdom, allow subcellular dissection, and easy DNA and antibody injection.

“A lot of people believe we know what we need to know about Aplysia, but I think there’s a great deal we don’t understand on a fundamental

level.”

With a primary research interest in memory maintenance, Dr. Glanzman uses Aplysia to explore the question of whether or not long-term memories can be altered. “This is a very important issue in our society. Think about post-traumatic stress disorder. How can we disassociate memories from the pain without erasing them?”

Dr. Glanzman’s recent work with Aplysia analyzed the effects of a protein synthesis inhibitor on an animal shortly after it is reminded of a prior experience. After a memory has gone through a period of protein synthesis dependency and is well consolidated, reactivating the long-term memory makes it once more vulnerable to disruption by inhibition of protein synthesis. This phenomenon, known as memory “reconsolidation”, suggests potential experimental avenues for developing effective treatments for post-traumatic stress disorder (PTSD).

In tandem with Aplysia, Dr. Glanzman works with a more complicated experimental model, zebrafish. He characterizes this complexity, “not in terms of the number of neurons in the animal, but in terms of the depth of our scientific understanding of the organism.” The major advantage of zebrafish over Aplysia is that the animal can be genetically manipulated.

Transgenic zebrafish can be engineered, and neurons can be transfected with calcium indicators or other optogenetic constructs. Zebrafish larvae are transparent, which allows researchers to place a calcium indicator dye in specific classes of neurons and study calcium signaling in intact behaving fish. The skin of fish is also permeable to drugs. Add a drug to water and it will be rapidly absorbed.

Dr. Glanzman’s zebrafish studies are focused on the simplest form of learning, habituation, which may be defined as the decline in responsiveness to the unchanging delivery of a specific stimulus. The process of habituation is highly adaptable and has maintained its function throughout evolutionary history. “If you wear a watch daily, yet aren’t consciously aware of it, it’s not because your sensory receptors aren’t transmitting signals. It’s because you have become habituated to the feeling of the watch on your wrist,” Dr. Glanzman explains.

In zebrafish, the habituation process manifests in the C-start, a reflex that contracts the animal’s body when it is startled, propelling it away from the intrusion in less than the blink of a human eye. The C-start is mediated by a pair of giant neurons in the brain stem of the fish. When these neurons fire, they activate motor neurons in the spinal cord, causing the C-start contraction.

After investigating this problem, Dr. Glanzman began to look at pre-pulse inhibition. “If you give someone a weaker stimulus before a stronger, startle-inducing stimulus, the strength of the startle reflex will be muted.” His most current experiment addresses this process by using transgenic touch-sensitive zebrafish mutants with a defective N-Methyl-D-aspartic acid (NMDA) receptor subunit to see if the animal exhibits impaired pre-pulse inhibition.

4 Neuroscience News 22(2)

The C-start reflex in zebrafish larvae. The white dot indicates

the initiation of the C-start reflex in response to an

auditory/vibrational pulse (counterclockwise). Image by

David Glanzman, edited by Roberts AC, Reichl J, et al PLoS

One 6: e29132, 2011.

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Since habituation is defective in schizophrenia and other psychiatric disorders, NMDA receptor function in this context could illuminate a pathway to possible treatments.

Dr. Glanzman doesn’t claim that his work with slugs and fish can be directly applied to humans. Rather, “Aplysia and zebrafish point the way to novel of approaches that you wouldn’t necessarily get with higher functioning organisms.”

“The human brain is the most complicated organism we know. It’s going to take a very long time to understand it. Ultimately, I am interested in the nervous systems of snails and fish because I think they offer the most direct paths to get us there.”

“The more proteins that we identify through transgenic animals, the more likely we are

to develop viable clinical treatments for humans.”

Dr. David Krantz, MD PhD, is a Professor in Residence in Psychiatry and Biobehavioral Sciences. At medical school his goal was to make a singular contribution to the understanding of mental illness. As a doctoral student at UCLA in the lab of Lawrence Zipursky, PhD, (now a Distinguished Professor of Biological Chemistry), he was exposed to the power of the experimental model, Drosophila, otherwise known as the fruit fly.

Like all animal models, Drosophila has its deficits. The fly has a larger number of neurons (~200,000) than Aplysia, but most fly neurons are tiny, with half of the fly brain equal in size to some individual Aplysia neurons. However, the fly model has been around since the early 1900s for a reason. It offers researchers unique research possibilities as well as a well-developed tool kit that has evolved over a century.

“At a cellular and molecular level, the animals are similar to humans. And the proteins I’ve been focusing on, neurotransmitter transporters, are very closely related to us.” In fact 70% of disease genes in mammals are present in flies. In addition, Dr. Krantz notes that, at the behavioral level, “despite the differences in anatomy, neurotransmitters in flies have remarkable functional evolutionary conservation.”

There is a large body of literature supporting the use of fly models to study neurodegenerative diseases. Dr. Krantz, however, is promoting the relatively new idea that fly models can yield valuable knowledge in the study of psychiatric illnesses.

“In Drosophila as well as mammals, animergic neurotransmitters such as dopamine and serotonin regulate behavior and mediate fast synaptic transmission, but we really don’t know how this works.” These processes have broad implications for a variety of mental illnesses, such as addiction. “When flies are on cocaine they run around, try to mate, and groom each other more. This behavior is surprisingly similar to humans on cocaine.”

In any basic science investigation related to mental illness, it will be critically important to understand how genes interact with each other, and to identify additional environmental contributions. Human patients harbor multiple risk alleles with small effect size, but scientists have no idea how these alleles interact with each other to cause the downstream effects that promote mental illness.

Flies are perfect for experiments in this context because they are easy to genetically manipulate. Researchers can quickly and cost-effectively express several genes in a fly to study complex genetic interaction. The model is also ideal for forward genetic screening, and it is relatively easy to screen thousands of animals. In addition, Drosophila’s relatively large number of neurons form a complex nervous system that generates behavioral traits

that are of a different order of magnitude than some simpler invertebrates.

Dr. Krantz is particularly determined to apply Drosophila to elucidate one of the most devastating illnesses facing the USA today. Fifteen percent of Americans grapple with depression, yet scientists don’t know

causality, don’t understand how anti-depressants work, and can’t define why it is that patients get better or worse. Dr. Krantz recognizes, though, that the fly model alone can’t provide the answers to such questions.

“It’s important to acknowledge that one particular cell type or system can be good for examining a specific question. However, it is not always obvious which system will be best suited to a particular question until you consider its specific biological characteristics. Conversely, just because there is one potentially insightful way to use a particular model doesn’t mean that we should study everything using that one model. This is certainly the case with worms, sea slugs, fish, and flies.”

“Every one of these systems can make an important contribution. It’s vital that we

develop them in parallel so that we have a multitude of different ways of looking at

difficult problems such as the way amines regulate behavior, or the genetics of mental

illness.”

Fly live imaging of aminergic neurons. Image by David Krantz

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Early in his career, X. William Yang, MD PhD, visited Lake Maracaibo, a poverty-stricken region of Venezuela that has been cursed, it seems, by an incidence of Huntington’s disease that is one hundred times higher than in other areas throughout the world. The disease (HD), which usually manifests in people in their 30s and 40s, is a neurodegenerative disorder characterized by progressive loss of movement, cognition, and other devastating psychiatric ailments. Because HD is genetic, many generations of the same families are affected. Young parents see their own health disintegrate with the knowledge that they have a 50/50 chance of being alive to see their children suffer the same fate. In the case of Lake Maracaibo, HD manifests in epidemic proportions.

Dr. Yang, Professor of Psychiatry & Biobehavioral Sciences at UCLA, visited Venezuela twice to spend time with the people of Maracaibo. The experience inspired him to embark on a career-long journey aimed at uncovering the mysteries of HD. In order to do this, he needed a key collaborator -- the transgenic mouse.

While invertebrates offer researchers an experimental model powered by clarity and simplicity, the mouse model provides opportunities to study an organism that is hundreds of millions years closer to humans on the evolutionary spectrum. The species shares clear homologies with humans. Mouse behavioral patterns, motor functions, and even certain cognitive processes have a fairly direct extrapolation to basic human functions. 30,000 of the 35,000 protein coding genes in the human genome are present in mice. And, also key to Dr. Yang’s work in HD, the model’s neurocircuitry is very similar to that in higher level mammals.

“The mouse model is one of the best mammalian genetic models that we

currently have.”Dr. Yang describes other major advantages. “A rigorous experiment is reliant on a sizable colony of subjects. Female mice breed very well, the animal grows quickly, and fathers don’t harm their young. Moreover, the mouse genome can be readily manipulated using modern molecular techniques to insert or delete a gene.”

These features facilitate the relatively speedy development of transgenic strains of mice.

When Dr. Yang first began to translate his observations from Maracaibo into directions for experimental design, he was quickly struck by the limitations of transgenic engineering at the time. “For any given gene in the genome to be accurately expressed, regulatory elements are essential. But in the 1990s, we could only use a small part of the DNA to generate transgenic mice. This meant that very often the transgenic mice could not confer accurate expression of the gene, and that we could only study a small portion of the gene.” Thus, studies at the time could not model human diseases in animals using the large DNA fragments that contain most, if not all, of the pivotal DNA elements similar to those in human patients.

In 1997, together with colleagues from Rockefeller University, Dr. Yang co-invented the first recombineering technology to modify large pieces of DNA -- bacterial artificial chromosomes (BACs), accompanied by the first protocol to insert BAC DNA into the mouse genome. BAC transgenic mice were born. Now one of the global standards for genetic engineering, this technology facilitates very accurate gene expression in transgenic mice.

With the invention of BACs, Dr. Yang now had a powerful weapon with which to begin untangling Huntington’s disease.

The huntingtin gene, discovered in 1993, is mutated to cause HD. “The protein is a huge gene and it’s expressed everywhere in the human body. So what causes the mutant huntingtin to be so toxic to the brain? And how does this disease protein cause age-dependent motor, cognitive and psychiatric symptoms in the patients?”

“Huntington’s disease is an enigma at a basic biological level.”

- II -WILLIAM YANG

&THE MOUSE

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In HD pathology the whole brain is shrinking, but the majority of neurons that are being lost reside in the striatum. For decades researchers assumed that the striatum was the sole operator in HD. Dr. Yang, however, took a fresh, unbiased approach to study the question of selective neuronal vulnerability in the disease. “I didn’t want to assume anything,” he says.

The striatum is part of the basal ganglia, which is in two-way communication with the cortex. “Why should we assume that the cortex is secondary to the disease?. Does mutant huntingtin affect the striatal neurons alone? Is it possible that other cells are giving these neurons toxic signals or withdrawing help?”

In 2002, these big questions prompted Dr. Yang to set up his lab at UCLA with the goal of using mouse models not just to recapitulate aspects of HD symptoms and pathology, but in a way that allowed him to study the distinctive roles of different cell types in the disease, particularly those in the striatum and cortex.

Together with lab colleague Dr. Xiaofeng Gu, Dr. Yang spent the next few years developing strains of mice with a fragment of the huntingtin gene switched on. The initial experiment analyzed whether it was intrinsic toxicities within mutant huntingtin cells or toxicities originating from other cells that could be the cause of HD disease phenotypes.

Drs. Yang and Gu discovered that mutant huntingtin in neighboring cells can elicit pathological cell-to-cell interactions that appear to impact both cortical and striatal neurons, activating the disease in their HD mice. This was a significant advance at the time, “but the experiment didn’t define where the toxicity originates. It was incomplete because we used a model that expressed only a small fragment of mutant huntingtin. We needed to express a full length protein in order to be genetically more homologous to humans.”

Almost ten years ago, Dr. Yang began this next chapter. “We wanted to develop BACHD -- a transgenic mouse model with a very large segment of human genomic DNA, one that contains the entire huntingtin gene. I knew it was going to be a long-term experiment, but I was also certain that it would be important to pursue. ” Dr. Yang and post-doctoral students Dr. Michelle Gray and Dr. Nan Wang successfully tailor-designed the BACHD model so that the disease gene could be switched off in different cell types. “With such a model, my lab now had the tools to gain new insights into whether mutant huntingtin is synthesized in the striatal neurons, the cortical neurons, or whether both play a role in eliciting the disease.” The BACHD model developed in Dr. Yang’s lab has since become one of the most widely used HD mouse models in the world.

The next stage of Dr. Yang’s investigation utilized Cre, a genetic scissor, to excise mutant huntingtin genes in Cre-expressing cells. By crossing BACHD with various Cre mouse lines, mutant proteins were removed from cortical neurons, striatal neurons, or both.

The mice were then analyzed at multiple ages to evaluate the effect of removal of mutant huntingtin expression in a specific set of neurons, while leaving the disease protein expressed elsewhere in the brain and body. Dr. Wang measured motor functions, depression-like behaviors and anxiety levels, comparing disease progression where mutant proteins were reduced in cortical and/or striatal neurons. The conclusions ran somewhat contrary to more traditional thinking that had assumed that HD was mostly a striatal disease.

“We were surprised to see that when we reduce huntingtin in the cortical region, there are large improvements in psychiatric-like symptoms and modest improvements in motor functions. When we reduce mutant huntingtin in the striatal neurons alone, the improvements are much more limited.” Most importantly though, “when we reduce mutant huntingtin in the striatal and cortical regions, there is a remarkable improvement in every disease phenotype measured in our BACHD model.”

“The transgenic mouse model has taught us, for the first time, that Huntington’s

disease is likely caused by neuronal miscommunication between the cortex,

and the striatum.”

In June 2012, the journal Neuron published an article co-written by Dr. Yang, in which he summarizes the promise of a therapeutic strategy to degrade huntingtin mRNA. This resulted in amelioration of symptoms in HD mice. At the time, he wrote that “we need to know when in the disease course and where in the brain such therapies should be delivered.”

This year, Dr. Yang and his team of scientists made the cover of Nature Medicine, with findings that provide some answers to where such therapies should be administered. Since his study suggests that these therapies may be optimized when delivered to the cortex and striatum, it is likely that this recent work will inform some upcoming clinical trials aiming to deliver mutant huntingtin-lowering therapeutics into the human brain.

“When I stayed in Lake Maracaibo and worked in a community that was suffering in such an unimaginable way, I become convinced the Huntington’s disease was a question that is scientifically solvable, and one that had to be solved.”

Due to Dr. Yang’s career-long mission accompanied by his transgenic mouse models, a solution may indeed be just around the corner.

Facing page: Image of the Huntington brain, courtesy of William Yang

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8 Neuroscience News 22(2)

-III- SEX DIFFERENCE IN ANIMAL MODELS

Thanks partly to the research of Rhonda Voskuhl, MD, and Art Arnold, PhD, the National Institutes of Health has announced a change in policy regarding the inclusion of both sexes in animal research. The NIH announcement, authored by Janine Clayton, Director of the US National Institutes of Health Office of Research on Women’s Health, and Francis Collins, Director of the NIH, was published in the May 2014 edition of Nature. Drs Clayton and Collins target convention as “a probable reason for reliance on the male-only models that have been typical in many research areas for decades. Lack of understanding about the potential magnitude of the effect of sex on the outcome being measured is likely to perpetuate this blind spot.” They warn that “the over-reliance on male animals and cells in preclinical research obscures key sex differences that could guide clinical studies. And it might be harmful: women experience higher rates of adverse drug reactions than men do.” In the article, the NIH leaders describe work in multiple sclerosis (MS) and obesity to exemplify the power and necessity of sex differentiation in animal models and clinical contexts. One third of the publications cited originated from the BRI’s Laboratory of Neuroendocrinology (LNE).

LNE Director, Art Arnold is a Distinguished Professor in Integrative Biology & Physiology. Dr. Arnold and his colleagues seek to elucidate the biological factors that cause the sexes to react differently to a variety of diseases including obesity. In doing so, the Arnold lab has become a standard bearer for the importance of sex difference in studies using animal models. The NIH announcement cites a recent publication from the Arnold lab in collaboration with the lab of Dr. Karen Reue, Professor of Human Genetics, reporting that the number of X chromosomes within cells contribute to sex dimorphism in body weight, fat distribution, and metabolic disease (Chen et al., PLoS Genet 8, 2012). Previous to this work, sex differences of this sort were attributed exclusively to effects of gonadal hormones.

Dr. Arnold explains, “The study of sex differences has undergone a major change in the last 20 years. Previously, sex differences were studied mostly in connection with reproduction, where the sexes differ dramatically. More recently it has become apparent that sex biasing factors, including hormones and the sex chromosomes themselves, act throughout the body differently in the two sexes to change physiology and alter the course of disease. The new NIH policy aims to reverse the long-standing over-emphasis on the study of males, and thereby improve the quality of basic biomedical science.”

Like Dr. Arnold, Dr. Voskuhl, Professor of Neurology and Director of the UCLA Multiple Sclerosis Program, has had a large impact on the new NIH focus on studying sex differences in animal models. Dr. Voskuhl first tested the hypothesis that pregnancy protects women from MS relapses using the rodent experimental encephalomyelitis animal model. Initial studies identified estriol, a hormone that spikes during pregnancy but is virtually undetectable otherwise, as a protective factor. This year, Dr. Voskuhl presented the preliminary results of a Phase II clinical trial that administered estriol with Copaxone (the current treatment for MS) to 158 women with relapsing-remitting MS. The result was dramatic: the relapse rate was reduced by nearly fifty percent during the first year of treatment.

“In the past, sex differences in physiology and disease were viewed by many as confounding variables to be eliminated or bypassed, often through the use of only one sex in basic experiments and clinical trials. The present NIH policy revision will pave the way for scientists to embrace and focus upon sex differences as helpful clues leading to a better understanding of physiology and disease,” Dr. Voskuhl says. “This is a paradigm shift in the research approach. It will likely not only provide better tailoring of disease treatments for each sex, but also lead to the discovery of novel treatments for disease.”

Because of work done by Drs. Voskuhl and Arnold and researchers like them, the NIH will now require sex and gender inclusion in all plans for preclinical research. By doing so, Drs. Clayton and Collins state, “the NIH will ensure that the health of the United States is being served by supporting science that meets the highest standards of rigor.”

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The Twenty-Second Annual Samuel Eiduson Student Lecture Award

This year, the Twenty-Second Annual Samuel Eiduson Student Lecture was presented by Saturo Miura, PhD, from the Department of Biological Chemistry PhD Program and the Zipursky lab.

Larry Zipursky, Distinguished Professor in Biological Chemistry, introduced Dr. Miura as “the kind of grad student that all thesis advisors love to have -- smart, creative, someone who challenged authority and worked tirelessly.” Saturo set out to understand a major challenge in the Zipursky lab -- how Down syndrome cell adhesion molecule (DSCAM) isoforms are regulated during splicing. “Saturo is a rigorous investigator. There were many times during this project that he could have taken a shortcut, but he was always set on doing experiments in the most comprehensive way to get answers that would thoroughly address the underlying questions.”

Dr. Miura, now a postdoctoral research fellow at the University of California, San Diego, presented, “No two neurons are the same: unique identities for neural circuit assembly,” to the neuroscience community on May 20, 2014.

Dr. Samuel Eiduson served as Chair of the Interdepartmental Graduate Program for Neuroscience from its inception in 1972 until 1985. He was an exceptional educator and mentor, and was instrumental in advancing the careers of many UCLA neuroscientists and graduates.

The Twenty-Fifth Annual H.W. Magoun Lecture

The 2014 H.W. Magoun Lecture was presented by Alcino Silva, PhD, Professor of Neurobiology, Psychiatry & Biobehavioral Sciences, and Psychology. Dr. Silva’s lecture, entitled “The exciting road from mechanisms of learning to the treatment of cognitive disorders” focused on the means by which mouse model studies have uncovered mechanisms and treatments for learning and memory disorders, that may lead to adult treatments for neurodevelopmental and other learning and memory disorders.

Horace “Tid” Magoun (1907-1991) founded the Brain Research Institute on the UCLA campus in 1959, driven by the goal of establishing an interdisciplinary research center. He was known for encouraging, facilitating, promoting, and disseminating the work of other researchers in order to advance the BRI mission.

FEATURED EVENTS

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THE BRI WELCOMES NEW MEMBERSPAMELA KENNEDY, PhD, ASSISTANT PROFESSOR OF PSYCHOLOGY

Pamela Kennedy, PhD, comes to the BRI from Mount Sinai School of Medicine. As a doctoral student, she studied how memory and motivational states interact to guide goal directed behavior. Near the end of her graduate school term, though, something happened to expand that focus.

“Neuroscience first attracted me because it can always relate somehow to what is happening in our own lives,” she says. “In this case, my grandmother had a fall, accompanied by a small ischemic event resulting in loss of memory. She’d always been a heavy smoker but, in the aftermath, she didn’t crave a cigarette and had no withdrawal symptoms. She asked for a cigarette only after her memory was almost fully restored. By then it was easy to convince her that since she hadn’t smoked for months, she didn’t need to light up again. She hasn’t touched a cigarette since.”

Dr. Kennedy became interested in the mechanisms of drug addiction and their interactions with learning and memory. As a postdoctoral researcher, she investigated the molecular changes that affect how neurons communicate. At UCLA, “I plan to research reward circuitry and memory systems, and the process through which a habit system versus an episodic system takes hold of behavior. This should shed light on how communication is altered between different parts of the brain during the process of addiction.”

By combining electrophysiological tools and molecular underpinnings, Dr. Kennedy hopes to pinpoint differences across structures in the brain in tandem with articulating differences in gene transcription and molecular changes within individual regions. “With the support of the learning and memory community and the addiction researchers, I know I’m in the right place. Communication between basic and clinical scientists here is very open compared to other institutions, and the possibilities for translational discoveries are strong.”

When Dr. Kennedy got the news that she was hired at UCLA, she was reminded of a family road trip across the country at age nine. “My mother didn’t say anything until the hire was official, but once it was, she told me that when we stopped to visit UCLA during that childhood road trip, I announced that I would go there one day.”

ANDREW J. FULIGNI, PhD, PROFESSOR OF PSYCHIATRY & BIOBEHAVIORAL SCIENCES

Dr. Fuligni received his Ph.D. in developmental psychology from the University of Michigan and was previously an Associate Professor in the Department of Psychology at New York University.

His major areas of interest are neural and biological mechanisms of the impact of social and cultural experience in health and development during adolescence. In collaboration with colleagues at the Semel Institute and in Psychology, he is conducting an NIH-supported longitudinal study of the impact of social experience on neural development and biological markers in health amongst adolescents from diverse ethnic and immigrant backgrounds.

Dr. Fuligni is currently Co-Director of the NIMH Family Research Consortium IV.

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THE BRI WELCOMES NEW MEMBERSRAJESH KUMAR, PhD, ASSISTANT PROFESSOR OF ANESTHESIOLOGY AND RADIOLOGICAL SCIENCES

Dr. Kumar received his PhD in radiology from the Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, UP, India. His current research involves the evaluation of neural tissue integrity, resulting from breathing or cardiovascular effects, in brain areas of patients with obstructive sleep apnea (OSA) and heart failure (HF). His goal is to understand the brain processes by which autonomic, memory, and mood regulations are affected in these conditions.

Dr. Kumar employs magnetic resonance spectroscopy (MRS) and various magnetic resonance imaging (MRI) procedures (including high-resolution T1-weighted imaging, T2-relaxometry, magnetization transfer imaging, diffusional kurtosis imaging, diffusion tensor imaging, arterial spin labeling, and functional magnetic resonance imaging) to assist in the localization of abnormal brain regions and assess neural activity in patients with OSA and HF. He has demonstrated that HF patients show brain injury in autonomic, mood, and cognitive regulatory areas, has differentiated different types of white matter injury (axonal or myelin injury), and showed that HF subjects exhibit more neural damage than OSA patients, particularly in brain areas that serve memory functions and which, if damaged, can contribute to depression. Dr. Kumar seeks to determine the onset of the neural damage in HF and OSA, the specific cardiovascular or breathing effects that the damage could exert, and the extent of progression as the syndrome continues. These findings could lead to preventative measures before the severe consequences, such as hypertension, stroke, and daytime hypersomnia in OSA patients, and autonomic, mood, and cognitive deficits including memory issues

in HF patients.

Dr. Kumar’s research aims to be of value for both early identification of problems, and to give greater understanding of the causes of HF and OSA.

BENJAMIN ELLINGSON, PhD, ASSISTANT PROFESSOR OF RADIOLOGICAL SCIENCES

Dr. Ellingson received his Ph.D. in functional imaging at Marquette University and Medical College of Wisconsin. He came to UCLA after a fellowship in Radiology at the latter institute.

Dr. Ellingson’s major areas of research include advanced MRI and positron emission tomography (PET) techniques for brain tumor treatment evaluation, characterization, visualization and quantification. He is involved in image protocol development, standardization, and quality control for multicenter clinical trials in a variety of brain tumor clinical trial consortiums. He is interested in the development and testing of new imaging biomarkers for novel brain tumor therapies as well as radiogenomics, high-dimensional imaging analyses, and voxelwise spatiotemporal modeling of regenerative and degenerative neuropathologies using advanced imaging techniques.

Dr. Ellingson is Chair of the Neuro-Imaging Committee of the Adult Brain Tumor Consortium, and Co-Chair, Neuro-Imaging, of the Ivy Foundation Clinical Trials Consortium. He is currently the Principal Investigator of the “Advanced imaging analysis for glioblastoma patients in the AVAglio trial”, funded by Genentech/Roche Inc.

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NEW MEMBERS... cont’dGREGORY A. MILLER, PhD, DISTINGUISHED PROFESSOR & CHAIR OF PSYCHOLOGY, DISTINGUISHED PROFESSOR OF PSYCHIATRY & BIOBEHAVIORAL SCIENCES

Dr. Miller received his PhD at the University of Wisconsin-Madison.

Dr. Miller’s research focuses on brain mechanisms relating cognitive, emotional, and physiological aspects of normal and abnormal human behavior, using methods of cognitive, affective and clinical psychophysiology, and neuroscience. Brain-region functional connectivity in disorders such as depression, anxiety and schizophrenia are of particular interest to him. Dr. Miller studies executive function, emotional dysregulation, and sensory processes, as well as development of multimodal neuroimaging methods. His research integrates sMRI, fMRI, and dense-array scalp event-related brain potential (EEG/ERP) and magnetoencephalography (MEG) measures as well as structured diagnostic interviews and neuropsychological testing.

SAMANTHA BUTLER, PhD, ASSISTANT PROFESSOR OF NEUROBIOLOGY

Dr. Butler received her PhD in molecular biology at Princeton University. Her underlying research interests are developmental neurogenetics and neural regeneration.

The extraordinarily diverse functions of the nervous system, from cognition to movement, are possible because neurons are assembled into precisely ordered networks that permit them to rapidly and accurately communicate with their synaptic targets. Dr. Butler aims to understand the mechanisms that establish these neuronal networks during development with the long-term goal of determining how this process may be co-opted to regenerate damaged circuits. Her research has shown that molecules previously identified as morphogens can act as axon guidance signals. She has also determined how neurons translate morphogens, specifically the bone morphogenetic protein family of growth factors over time, to mediate strikingly different processes in the generation of neural circuits.

During the course of these studies, Dr. Butler further identified a critical mechanism by which the rate of axon outgrowth is controlled during development. Her laboratory is currently using animal model systems to determine how this mechanism can be harnessed to accelerate axon growth in a regenerative context to stimulate the repair of neural circuits. The successful implementation of this technology could result in significantly improved recovery times for patients with nervous system damage.

ALAPAKKAM P. SAMPATH, PhD, ASSOCIATE PROFESSOR OF OPHTHALMOLOGY, JULES STEIN INSTITUTE

Dr. Sampath received his PhD at UCLA, followed by postdoctoral appointments at Stanford University and the University of Washington.

His research aims to understand how signals that are generated by retinal photoreceptor cells (rods and cones) are processed by retinal circuits which lead to visual experience. To study this relationship, Dr. Sampath records the light-evoked activity of mouse retinal cells using physiological methods. This approach facilitates the elucidation of mechanisms that influence the fidelity of light-evoked signals as they move through the circuitry to the retinal output. Behavioral experiments on control and transgenic mice subsequently allow for the determination of how these signals set visual thresholds. Dr. Sampath is currently pursuing several lines of experiments designed to determine the limiting noise in rod photoreceptors for seeing, and determining how the retinal circuitry switches from being rod-dominated to cone-dominated as light levels increase.

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AWARDS & ACKNOWLEDGMENTS

The Research Society on Alcoholism (RSA) has awarded Lara Ray, PhD, the 2014 Young Investigator Award, presented in recognition of her discoveries in the pharmacogenomics of alcohol response and alcoholism treatment. An Associate Professor of Psychology, Dr. Ray integrates psychopathology, behavioral genetics, pharmacology, and neuroimaging to study the etiology and treatment of substance abuse disorders.

In its award letter, the RSA describes Dr. Ray as “a role model for the new era of behavioral genetic research being applied by Clinical/Experimental Psychologists. (She is) a versatile, young scientist who employs a wide range of investigational techniques to study drinking and related phenomena in both controlled and naturalistic environments. (Her) work is highly translational and holds great promise for bridging clinical investigation with basic, preclinical research.”

The National Institute of Biomedical Imaging and Bioengineering has awarded Dr. Daniel Lu (right), Assistant Professor of Neurosurgery and Orthopedic Surgery, and Co-Director of the Spinal Cord Rehabilitation Center at UCLA (below), and Dr. V. Reggie Edgerton (left), Distinguished Professor of Neurobiology and Neurosurgery, a $6 million, five-year grant to explore new therapies for the approximately 273,000 Americans living with spinal-cord injuries. The research will focus on restoring hand function to patients paralyzed from the neck down. Cervical spinal-cord injuries — those involving the neck — make up more than half of the cases in the U.S. While seeking to help people with cervical spinal-cord injuries regain the use of their hands, the UCLA team is looking to build on findings from Edgerton’s earlier work, conducted with Russian scientist Yury Gerasimenko, on lumbar spinal-cord injuries.

David Jentsch, PhD, Professor of Psychiatry and Psychology, and Dario Ringach, PhD, Professor of Neurobiology and Psychology, have received the 2014 Biomedical Research Leadership Award from the California Biomedical Research Association.

Drs. Jentsch (upper right) and Ringach were selected in recognition of their dedicated work in the field of biomedical research and for the roles they have played nationally in calling attention to the need for public outreach, advocacy and education on the issue of the humane use of animals in biomedical research and discovery. They have spotlighted the challenges and illegal actions by extremists that researchers face daily, and the critical need for education and outreach to the general public, the media and amongst students.

The two professors were previously honored by the American Association for the Advancement of Science for bravery in the face of threats from extremists.

Dr. Jentsch’s research focuses on the neurobiological mechanisms that lead to the loss of self-control in addictive disorders. He and a colleague from Yale University proposed the view that the relapsing nature of drug and alcohol addictions may be best explained by a pathology within brain circuits involved in the inhibitory control of behavior.

Dr. Ringach’s research interests include visual neurophysiology and perception. He studies cortical dynamics, circuitry, function and mathematical modeling of receptive fields.

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Gary Small, MD, Professor of Psychiatry and Director of the UCLA Longevity Center, has been appointed President-Elect of the American Association for Geriatric Psychiatry, a national nonprofit organization that promotes the mental health and well-being of older adults through professional education, public advocacy, and support of career development in geriatric psychiatry and mental health.

Dr. Small’s team has developed neuroimaging technologies that detect the first signs of brain aging and Alzheimer’s disease years before patients show symptoms. In addition to testing medicines that might delay the onset of Alzheimer’s disease, Dr. Small has developed nationwide training programs that support a healthy aging lifestyle and memory.

Scientific American magazine named him one of the world’s top 50 innovators in science and technology

Jesse Rissman, PhD, is the recipient of a Faculty Career Development Award. Dr. Rissman, an Assistant Professor of Psychology, uses behavioral and neuroimaging techniques to study the mechanisms of human memory. One of his major interests is understanding how the brain flexibly regulates the formation, maintenance, and retrieval of memories depending on present circumstances and goals.

The award is one of twenty-seven announced by the UCLA Faculty Diversity & Development Office. Its goal is to support faculty members at a critical time in the pre-tenure period of their career.

AWARDS & ACKNOWLEDGMENTS cont’d

The BRI, the Integrative Center for Neural Repair and the CTSI have funded four projects as part of a pilot program for neurodegenerative disease-related research.

Michele Basso, PhD, a Professor of Psychiatry and Director of the Fuster Laboratory of Cognitive Neuroscience, will develop a new model of slowly progressing degeneration in Parkinson’s disease. Peyman Golshani, PhD, an Assistant Professor of Neurology, will image pathological network dynamics in Huntington’s disease. Jason Hinman, MD, PhD, an Assistant Professor of Neurology, will study the molecular synergism between white matter stroke and Alzheimer’s disease. Felix Schweizer, PhD, a Professor and Vice Chair for Education in Neurobiology and Chair of the Interdepartmental Graduate Program in Neuroscience, will investigate neuronal effects of PD related pesticides.

Ira Kurtz, MD, Professor of Medicine, has received a $3 million gift from the Donald T. Sterling Foundation to fund research on the structural properties of key proteins in the kidney that affect its function in health and disease. His ultimate aim is the discovery of new molecular approaches which will aid in the development of drugs to treat patients with kidney disorders. “This gift will play a key role in accelerating the success of ongoing research projects in my lab,” said Kurtz, who holds the Factor Chair in Nephrology and serves as Chief of the Division of Nephrology at UCLA. “There is a worldwide epidemic of kidney disease today. More than 500 million people worldwide have some form of kidney damage. Millions of people are affected and die each year.”

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Next-Generation NEUROS-THE BRI REACHES OUT-

BRAIN AWARENESS WEEK BRINGS TWEENS AND TEENS TO THE UCLA CAMPUS

Brain Awareness Week is an annual international event, inviting K-12 students to university campuses all over the world in order to experience the wonders and opportunities of neuroscience.

This year, UCLA Brain Awareness Week activities, which are sponsored by the BRI, brought over 300 students from underserved schools in the Los Angeles Unified School District.

Activities provided fun, interactive education about the brain and the central nervous system. Over 50 undergraduate and graduate student volunteers led educational activities, demonstrations, career and mentoring workshops, and lab and campus tours.

Each day began with a series of demonstrations designed to provide the students with inspiring information about brains, cells, and the senses. The days ended with guided lab and campus tours.

“We hope that the students left Brain Awareness Week with an appreciation for basic neuroscience concepts, and new excitement about the potential for a career in neuroscience at UCLA,” said BRI Director, Chris Evans.

RECORD TURNOUT OF MIDDLE AND HIGH SCHOOL STUDENTS COMPETE IN THE LOS ANGELES BRAIN BEE

The Los Angeles Brain Bee, coordinated by Interaxon, the Brain Research Institute, the University of California Irvine, the University of Southern California, and Los Angeles Community College, had a record number of attendees in 2014. Over eighty young people from all over Southern California came to campus to test their neuroscience knowledge, culminating in a Jeopardy-style competition for the finalists.

The Brain Bee is an international program aimed at motivating youth to pursue careers in neuroscience. The winner of the Los Angeles Brain Bee this year, Tustin District High School junior, Shyam Chandrasekar, said he enjoyed studying in preparation. “I like memorizing and understanding the concepts that go into action potentials and learning disorders,” he says.

Shyam Chandrasekar (center) with his mother and brother,

after winning the 2014 Los Angeles Brain Bee.

Shyam went on to place 12th in the National Brain Bee, which was held in Maryland. “It was great to see the many different avenues I can take in terms of my educational future. I’m definitely going to be a neuro-something.”

BRI AWARDS SPECIAL PRIZES FOR BRAIN RESEARCH AT THE CALIFORNIA STATE SCIENCE FAIR

Dr. Chris Evans and BRI Associate Director for Outreach, Dr. Ellen Carpenter, were on-site to award several prizes recognizing outstanding science projects in all areas of neuroscience from molecules to mind. The BRI State Fair Award was given to Pravin Ravishanker, from Santa Clara County, for his project, “Genetics or Gender? Effect of the APOE-e4 and Gender on Age-Related Brain Atrophy and Cognitive Decline in Alzheimer’s”. Junior division winner, Mythri Ambatipudi, also from Santa Clara, went on to become the division winner for the whole Science Fair. Her project, “Break the AGE Barrier! Inhibit Advanced Glycation End-products to Combat Atherosclerosis, Cancer, and Diabetic Disorders”, was a State Fair standout.

After winning on the Los Angeles County Science Fair, twelve year-old Portia Osuch also competed in the State Fair. Her mother, Nancy Osuch, Media Coordinator for the Easton Center for Alzheimer’s Disease Research at UCLA, credits Portia’s exposure to UCLA neuroscience for inspiring her to pursue a career in the medical field. Portia’s project, “Kicking It”, measured which tae kwan do moves generate the most force.

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Above: During Brain Awareness Week, a middle schooler tries on a real human brain for size, during a student demonstration.

UCLA HOSTS THE FIRST EVER EMPOW-HER STEM DAY

Eighty female middle school students from low-income, underserved schools in Los Angeles visited UCLA for the first-ever “Empow-Her STEM Day,” where they received hands-on exposure to research in science and technology — from launching a rocket to touching a human brain — while learning about career opportunities for women in a range of fields, from neuroscience to physics.

The one-day event in May was co-sponsored by UCLA’s Business of Science Center, the Brain Research Institute, California NanoSystems Institute, Campus Programs Committee and the Graduate Student Association. It featured 16 interactive informational stations manned by UCLA graduate students, who demonstrated basic concepts in human brain research, computer science, nanoscience, physics, environmental science and more. The activities were followed by a campus tour.

The organizers used the event to inspire the students to pursue higher education and a career in STEM (science, technology, engineering and mathematics) fields.

In addition, the event brought together graduate students from a variety of STEM disciplines to help foster outreach collaborations and raise awareness about careers in the sciences.

“Empow-Her STEM Day” was organized by Advancing Women in Science and Engineering and the EmpowHer Institute, a nonprofit focused on empowering women and girls. Above: An Empower-Her volunteer shows middle-schoolers how to

extract their own DNA.

Below: Chris Evans emcees the Brain Bee’s semi-final round.Below: Students launch a rocket, while being filmed by a CBS

camera operator, during Empow-Her STEM Day.

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NSIDP graduate student Ryan Jones (left), and undergraduate Austin Jewison demonstrate the

structure of a neuron during Brain Awareness Week.

Brain Awareness Week activities included a vision control test. Students try to throw a ball into a hoop while wearing goggles that simulate effects of a

concussion.Back cover: The faulty disposal picture shows mitochondria (green) and faulty disposal (aberrant autophagosomes) (red) in a worm muscle cell. Image by Alexander van der Bliek.

High school students attend the Los Angeles Brain Bee for the first time.

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Neuroscience News is published by the Brain Research Institute of the

University of California, Los AngelesCorrespondence may be directed to:

[email protected] orNeuroscience News, Brain Research Institute UCLA,

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