the publication of the neurosciences institute

T H E P U B L I C A T I O N O F T H E N E U R O S C I E N C E S I N S T I T U T E

BrainMattersF a l l / W i n t e r 2 0 0 6

I t is often said that it is more rewarding tobuild bridges than walls. This is especiallytrue when studying the brain, which

involves so many disparate scientific disciplines.Elisabeth Walcott, Ph.D., is a scientist whosework at The Neurosciences Institute involvesbuilding and strengthening bridges that canlead to discoveries. Walcott’s most recentefforts have led to the novel use of a hybridtechnology that connects computer modelingwith living cells in lab experiments. The application of this new technology allowsobservations of real brain cells within a computer-generated synaptic environment to simulate what occurs in the brains ofbehaving animals.

Elisabeth Walcott:Building Bridges

2 BrainMatters Fall/Winter

As she pursues her groundbreakinginvestigation of brain function atthe level of synapses and smallgroups of neurons, ElisabethWalcott is simultaneously engagedin an equally fascinating and

much more personal experiment: to balance thechallenging dual roles of professional neuroscientistand dedicated mom. Her daughter Lila just turnedtwo years old.

“The demands of science and motherhood are both so great that balancing the two requiresplanning and discipline, as well as being flexibleand willing to modify my expectations,” saysWalcott. She is quick to give credit to her husband,Dr. Stephan Miller, and to the Institute for enablingher to attempt this juggling act. “I’ve been very fortunate,” Walcott says. “My husband has a busycareer as a medical writer, but he shares a lot of the childrearing and household duties, includingserving as the family chef. His contribution hasbeen crucial, especially during those frequent periodswhen I need to concentrate on my research. TheInstitute has also been tremendously understandingand supportive in every way possible. They’veallowed me to work part-time, which amounts to a four-day week, to accommodate my familyresponsibilities,” explains Walcott.

Walcott maximizes her productivity in thosefour days. As a Research Fellow in ExperimentalNeurobiology, she is an integral part of theInstitute’s cellular electrophysiology group. The primary focus of her work is to understand the

physiology of the microcircuitry in the cerebral cortex by recording the electrical activity of braincells in real time, under different physiological andpharmacological conditions. Walcott studiesrodent brain slices which can stay alive for up to12 hours outside the animal. Inserting them intoan apparatus that combines electrical recordingtools with various microscopy modes to visualizeindividual neurons, she can peer into the innerworkings of complex cortical circuits.

Walcott’s early interest in neuroscience, combinedwith her intense curiosity about the world, led herto major in psychobiology at Harvard. Later, as shedeveloped an interest in neurobiology, she enteredthe doctoral program in biology at the Universityof California, Irvine. There she dove into molecularbiochemistry, including assisting with a key studyon the effects of nicotine at the cellular level. “Atthe end of graduate school I felt as though I hadswung too far from my interests in the brain. I hadshifted from behavioral psychology to studyingneurotransmitter receptors in frog eggs, not evenneurons,” says Walcott.

The seeds of Walcott’s future were planted ayear before she got her Ph.D. when she visited The Neurosciences Institute. She was recruited by Ronald Langdon, a former Senior Fellow inExperimental Neurobiology, to help him study neuronal electrophysiology.

Her early contributions involved examininghow synaptic plasticity—communication betweenneurons at the level of synaptic connections—occurs in the neocortex. The neocortex is involved

“My goal is to understand howthe brain changes at the cellularlevel as a result of experience,and I hope to one day get ahandle on the altered brainfunctions that lead to behavioraldisorders.”

— Elisabeth Walcott

Phot

o: G

reg

O'L

ough

lin, w

ww

.Gre

gO.c

om

in higher functions such as sensory perception,conscious thought, generation of motor com-mands, and spatial reasoning. Synaptic plasticity isthe ability of the connection, or synapse, betweentwo neurons to change in strength. Memories arethought to be stored in synapses of the brain.Therefore, synaptic plasticity plays an importantrole in the process of learning and development of memory.

One important question was whether all brainsynapses were the same in their capacity to becomestrengthened or weakened with use. Walcottdemonstrated that unlike some other synapses, several types of neocortical synapses got weakervery quickly during a strong burst of stimulation.This type of short-term plasticity is temporary, but it is thought to be especially important in the neocortex for preventing runaway excitation, orepileptic-like activity, since the cortex is such ahighly interconnected structure.

Like many post-docs, Walcott envisioned staying at the Institute for two or three years.However, she was encouraged to stay on. As shetook on more responsibility and gained the respectand confidence of her fellow scientists, Walcottrealized she had found a home.

Currently, Walcott has been working with Niraj Desai, an Associate Fellow in ExperimentalNeurobiology, to make measurements in singleneurons that act like those found in the brain ofawake, behaving animals. To do this they tookadvantage of a system that combines real neuronsin a brain slice with computer-simulated eventsthat modify the neurons’ electrical and chemicalenvironment. This is a big step forward, as manystudies of synaptic communication have been conducted either in neuronal cultures that lackappropriate neuroanatomy or in “quiet” slices thatdo not have normal levels of neuronal activity. Theability to record from neurons in a more realisticenvironment will help provide detailed mechanismsfor behavioral changes observed in live animals andcould even be used to improve the types of testingavailable for potentially therapeutic drugs.

The two scientists used this hybrid method tostudy the effects of the potent brain chemicalacetylcholine on excitability of neurons in themotor region of the neocortex. Acetylcholine is a chemical released into the neocortex during periods of wakefulness, and it has been shown tobe required for certain types of learning. Notably, it is the acetylcholine-producing neurons that

Three neurons growing in culture stained to show cellular processes (color enhanced).


deteriorate in Alzheimer’s disease, so understandinghow they operate is of great interest. Walcott andDesai showed that acetylcholine increases theexcitability of neurons in the motor cortex. Thisincreased sensitivity might just be the thing thatallows plasticity and learning to occur.

Walcott believes that the work she is doingserves as an important bridge for many group projects at the Institute. In addition to her ownwork in the neocortex, she is eager to get involvedand learn about her colleagues’ projects. She hasrecorded from brainstem neurons as part of a modeling project with Eugene Izhikevich, fromlarge networks of neurons in cultures exposed tocaffeine with Fred Jones, and from developing neural precursor cells with Kathryn Crossin, allFellows at The Neurosciences Institute. However,she feels strongly that cellular neurophysiology ismore than a bridge. “It is a field unto itself withvast potential for generating breakthroughs of itsown,” says Walcott. She explains that our ability to observe how chemicals affect single neurons in a simulated “live system” can lead to technologythat will allow for better testing of the beneficialand harmful properties of new drugs.

The ultimate goal for Walcott, however, is oneshe acknowledges may take a few more years totrack down. “Wouldn’t it be amazing to see whatan abnormal brain circuit looks like in real time, ina human? Right now, there’s no way to do it. Onething that we can study is how synaptic activitylevels influence and shape responses of neurons indifferent brain regions. My goal is to understandhow the brain changes at the cellular level as aresult of experience, and I hope to one day get ahandle on the altered brain functions that lead tobehavioral disorders,” explains Walcott.

“The brain is vastly complicated and malleable,with circuitry that is puzzlingly adaptable. It’sgoing to take a lot of hard work to uncover thebrain’s underlying processes. I’m definitely onewho takes the long-range view of science. This fieldis so promising, and the technology is improvingso rapidly, that I know we’ll get there, even if ittakes a decade or more. When we do, I think we’llsee the development of some sophisticated

diagnostic and surgical tools that will turn the tideagainst many diseases,” says Walcott.

Despite the hectic schedule, Walcott actuallyseems to relish straddling her two worlds. “I lovegoing to the lab and really miss it when I’m notthere,” she says. “The thought of discovering something that no one has ever seen and whichmight benefit mankind is incredibly exciting. I alsolove being a mom. I’m committed to our familyand raising a healthy and happy child. WatchingLila develop and learn about the world at such anastonishing rate reminds me of how incredible thehuman body is, especially the brain. It makes merealize that my two lives aren’t really that separate.Right now, I’m enjoying the challenges of doingboth,” says Walcott.

“I am constantly searching for female rolemodels who have continued to work at the highestlevels of science while raising a family,” says Walcott.Ironically, while searching for the ideal role models,Walcott has become a strong role model herself, bybuilding bridges both in her cooperative work andbetween motherhood and a professional career inscience. Clearly, she has now joined the ranks of the many professionals who manage the challengesof raising their families while working towardsimportant scientific goals.

5BrainMatters Fall/Winter

T he rushing sound of the freeway traffic isa steady companion for the highway worker.

The waitress knows her busy restaurant is noisy,but she hardly notices as she races around fillingcustomer orders. Young people walk about withtheir iPods plugged into their ears and evenmake claims that they can study while listening tomusic. Our lives are well intertwined with manytypes of pleasurable and unpleasant sounds.

How is our brain changed, for better or worse,by sound? And when we listen, what factors influencewhat we actually hear? Different people listening to the same sounds might have completely differentperceptions, because our brain is not like a taperecorder, but instead it is actively interpreting theworld around us.

Two innovative scientists at The NeurosciencesInstitute, Drs. Weimin Zheng and John Iversen,focus on these fundamental questions about auditoryperception. Using complementary levels of analysis,they both look at how the brain responds or changesbased on our sound-related experiences. Zheng’sresearch is at the cellular level and focuses on howthe properties of individual neurons in the auditoryprocessing centers of the brain can change under avariety of sound exposure conditions. Iversen usesnon-invasive brain imaging to examine the activity

of many thousands of neurons to understand thefundamental brain mechanisms that enable us toperceive rhythm, music, and language. The twomay work on different projects, but they have agreat deal to talk about during their lunch hours at the Institute’s daily Fellows Symposium, wherethe Fellows gather to discuss their research andshare insights and new ideas.

Zheng, who is an Associate Fellow in ExperimentalNeurobiology, has carried out groundbreaking researchwhich shows that, in rats, continual exposure toseemingly harmless ambient noise can lead to arewiring of the brain’s auditory circuitry. Such a rewiring could impair our normal abilities to distinguish between sounds, to understand language,or to enjoy music. He was recently awarded $65,000by The San Diego Foundation’s Blasker-Rose-MiahScience & Technology Fund. This grant will allowhim to continue and expand his studies of changesin the brain’s hearing centers induced by long-termexposure to noise at intensity levels similar to thoseof human conversation, traffic noise, and manyworkplace environments.

Iversen, Karp Foundation Fellow in TheoreticalNeurobiology, studies how our mind shapes ourperception of the world. Perception is not simplythe passive recording of events in the world—ourminds are active participants in shaping what we

Do YouHear

What IHear?


perceive. He focuses especially on how we experiencecomplex patterns of sound as they unfold in time,a process that is the foundation of our capability tofind meaning in speech, music, and other soundsthat are central to our lives as humans.

In a recent study, he examined how we “hearthe beat” of music. The beat—what we clap or tapour foot to when listening to music—is actually aproduct of our mind as it interprets and organizesthe sonic rhythms. Using measurements of brainactivity in human volunteers listening to rhythmicsounds, Iversen is seeking to understand just howthe imagination influences perception in the brain.

Iversen and Zheng each bring their own specialapproaches to examine how the brain processesvarious types of sound.

“John is working in a higher, much more theoretical realm of auditory processing, whereasI’m working at a very basic level—looking at howthe neurons in the auditory system of the brainidentify and make sense of what the animal is hearing. But both of our investigations are showingthat the brain is remarkably plastic in its ability toprocess and adapt to changes in response to alltypes of auditory stimuli,” says Zheng.

“Normally, there is a well-organized map, calledthe tonotopic map, in the primary hearing centerof our brains that represents the pitch of sounds inan orderly way. This map is crucial in our daily lifefor understanding the spoken word, enjoyingmusic, and detecting and recognizing all sorts of sounds.”

Zheng’s findings showed that the regular map of the auditory cortex region (tonotopic map as shownabove, left) of the rat gets rearranged as a result ofexposure to noise (above, right). The different colorsindicate the regions that respond to the lowest tohighest frequencies of sound. The map in the noise-exposed rats showed a significantly disrupted pattern.The insets show the location of the auditory regionon the surface of the rat brain.

Zheng’s many years of research on experience-dependent neuroplasticity—the brain’s ability toreorganize itself based on an individual’s experience—has led him to theorize that the hearing problemsof millions of Americans may result not from eardamage caused solely by high sound levels or bynormal aging, but from alterations in the brain’sauditory circuitry resulting from its ongoing effortsto adapt to sounds in our environment.

Zheng is particularly interested in the brain’sresponse to “white” noise (sound containing a very

A Neural Plasticity Model

“Weimin Zheng thinks that hearing problems ofmillions of Americans may result not from eardamage caused solely by high sound levels or byaging, but from alterations in the brain’s auditory circuitry resulting from its effort toadapt to ordinary sounds in our environment.”

Low-Level

Noise Exposure

Hearing Center in Normal Rat

Hearing Center in Noise-Exposed Rat

Low High Low High


broad spectrum of frequencies) that is a normalpart of so many work environments. He exposedlaboratory rats for a month to continuous, low-level“white” noise that was no louder than the level ofnormal conversation. Mapping of the animal’s primaryauditory cortex before and after the experimentshowed that, even in that short period, a dramaticreorganization of the animal’s tonotopic map hadoccurred. Zheng then showed, using behavioraltests, that the animals had lost their ability to discriminate small pitch differences, suggesting that the map shift actually had a detrimental effecton the animal’s hearing.

“Discovering that the animals had lost some oftheir ability to distinguish between certain soundswas the critical finding, and it’s the one that hasme so concerned that people in all types of jobswith prevalent white noise may be suffering fromthese adaptive changes that may lead to significantbrain alteration,” says Zheng.

“Unlike the proven damaging effects of workingaround jet aircraft or playing in a rock band, thenoise level I used in my experiment was well withinthe safe workplace decibel limits established by thefederal Occupational Safety and Health Adminis-tration (OSHA),” Zheng adds. “This could meanthat millions of workers are unknowingly at risk for potential sound-induced changes that couldseverely affect their hearing abilities.”

Zheng hopes that publication of his researchwill spur government, consumer, and health groupsto take a closer look at the effects of ambient noise.

In the meantime, his own concern is so deep thathe has already begun a series of new experiments.

“Now that I know that sound-induced reorgan-ization in the brain is a reality, I’m testing whetherthe tonotopic map can be restored when the animalis returned to a normal sound environment,” Zhengsays. “If not, I’m going to test whether the brainmight have the ability to develop a new and differentmap that would enable the animal to go back andforth between the two environments and processsound properly in both.”

Zheng’s long-term goal for his research is evenmore ambitious. “Ultimately, what I want to showis how experience-dependent brain plasticityworks,” he says. “It’s this plasticity that forms thebasis of learning and memory. If we can betterunderstand the mechanisms, there’s an excellentchance we’ll be able to harness this plasticity tohelp people recover from brain damage or diseaseand perhaps to rejuvenate the brains of our agingpopulation.”

Iversen’s goal is to achieve a basic understandingof how the brain processes sounds. In his researchhe has been able to combine a lifelong passion fordrumming, which he learned to do before he everwalked, with a deep interest in how the brain functions.

“I’m fascinated with rhythm and how what wehear—or think we hear—influences brain activity,”Iversen says. “In particular, I’m intrigued by theconcept that our perceptions of the world are notjust a passive recording of stimuli, but rather they

“John Iversen, who has had a lifelong interestin Japanese taiko drumming, is looking toachieve a deeper understanding of how thebrain processes rhythmic sound.”


reflect constructive mental processes in which ourinterpretation shapes what we perceive.

“When we hear music, for example, the perceptualexperience of a rhythm depends on how the listenerinterprets the meter—where in the sequence ofnotes they hear the downbeat. While the locationof the beat is often implied and supported by the music, it is in fact subject to our control,” says Iversen.

In his recent work on the mechanisms ofrhythm perception, Iversen works with volunteerswho sit in a magnetoencephalography (MEG)machine that measures, in real time, the minutemagnetic fields produced by electrical activity inthe brain. During the experiment, the volunteerfirst listens to repeated pairs of two identical tonesthat have no inherent beat. After brain responsesare measured during that baseline session, the subjectis then asked to imagine the beat on the first tone,and then, in a separate series, on the second tone.Where they imagine the beat to fall dramaticallychanges the perception of the rhythm.

“Because the actual tone stimulus remainedunchanged in this experiment, and the only thingthat changed was the individual’s own experienceinternally, the experiment really allowed us toexamine how a listener’s imagination—‘marching to the beat of one’s own drum’—can change what’shappening in our brain,” Iversen explains.

The fascinating result was that the brain respondedmore strongly to the tone with the imagined beat,although the tones were not different in loudness.Iversen has also shown that listening to a tone that is louder has just the sameboosting effect.

“The brain responses appearto originate in the auditory cortex,suggesting that imagining thedownbeat actually modifiesbrain responses to sound at anearly stage, maybe even changingperception,” Iversen says. “Asecond interpretation, based onthe known role of these brainsignals in motor processing andlong-distance coupling in thebrain, suggests that the motor

system is an essential component of a purely perceptual act.”

For Iversen, this opens up an entirely newworld to research. “I’m excited about where this isgoing to lead. Discovering this connection betweenthe brain’s auditory and motor systems has trulywide-ranging implications for the integration ofperception and action,” he says. Finding a brainresponse that is sensitive to a listener’s imaginationopens up possibilities not only for understandinghow we create our perceptions, but also it couldlead to new kinds of brain-computer interfacesallowing people to control a computer by “justthinking.” It also has implications for new thera-pies using rhythm to help people suffering frommovement disorders, such as Parkinson’s disease.

What will be next for the two? Iversen andZheng will continue to pursue their questions intheir immediate research areas. However, possibilitiesfor their collaboration at the Institute, whichencourages creativity and flexible interactionsamong researchers, are endless. By combiningforces, they could begin to approach fundamentalquestions about the links between mind and brain.How does our rich perception of the world arisefrom the activity of neurons? Does noise exposurealso affect the perception of the timing of sounds,as well as the frequency? Will rhythm and musictherapy reorganize sensory maps in the brain, perhaps leading to the development of treatmentmethods for serious neurodegenerative disorders?These are just a few examples of the possibilitiesthat these two colleagues might explore.

How do we study the brain?

Time(seconds)

Am

plitu

de(p

ico

Tesl

a)

Method: MEG scannermeasures brain activity

in real time

Map of auditoryresponse

The brain’s responseto sound

MEG Scanner Photo: 4-D Neuroimaging

The Neurosciences Institute celebrated 25 years of pioneering brain research on Saturday, September 30.

Dr. Gerald Edelman, the Founder and Director of theInstitute, described some of the Institute’s major researchdiscoveries and advances along with a historical review ofactivities from 1981-2006. Several of the Senior Fellows presented their recent research. Jeffrey Krichmar highlightedthe latest on brain-based devices; Eugene Izhikevich showedhow computers can be used to simulate the brain; RalphGreenspan gave an account of how genes influence behaviorin fruit flies; Fred Jones related how genes in nerve cells areaffected by caffeine; and Ani Patel spoke about the advancesin studies relating music, language, and the brain. The eventbrought together over 250 community members interestedin learning about the Institute’s research innovations andtheir potential for future applications. After the presentations,guests celebrated this landmark birthday at a reception inthe Institute’s plaza.

&F A L L / W I N T E R 2 0 0 6

NewsEvents

Minding the Brain – Celebrating 25 Years of Advances in Brain Research

Minding the Brain Celebration from top down and left to right:

Patti Cooprider and Lou Alpinieri,Lewis Cullman and Gerald Edelman,

Lucy Killea, Reena Horowitz,Reception in the Plaza.



Fifth Annual Minding the Arts Gala

The Institute’s fifth annual Minding the Arts benefitto support our performing arts program was held

on Sunday, September 17. Chaired once again byLinda Satz, with Lael and Jay Kovtun as HonoraryChairs, the event raised funds so that the Institute cancontinue to make its acoustically superb auditoriumavailable at no charge to local nonprofit arts and educational organizations. Dr. Nicolas Reveles, theGeisel Director of Education at the San Diego Opera,was the Master of Ceremonies.

The event included an outdoor cocktail receptionamidst the stunning architecture of the Institute’s campus, followed by a concert in the auditorium. The concert featured operatic vocal performances fromDaniel Hendrick and Elliott Wulff of The Hendrick-Montaño Artist Foundation, classical Persian music of The Darvak Ensemble, presented by The Center forWorld Music and Persian Cultural Center, and a Haydnpiano sonata by Anne-Marie McDermott, presented byMainly Mozart. In addition to the artists, who donatedtheir efforts, many local vendors generously donatedfood and beverage stations. Our thanks go to A.R.Valentien at The Lodge at Torrey Pines, Best BeverageCatering Company, Elegant Events Catering Company,the Fish Market, FRESH Seafood Restaurant and Bar,Girard Gourmet, Gourmet Group Catering, OrfilaVineyard & Winery, Sammy’s Woodfired Pizza, St.Tropez Bakery & Bistro, Sydney Frank Importing – JCCognac, TK&A Custom Catering, Top of the Cove,Greene Music, and Sharrie Woods Floral Design.

We are truly grateful to our Minding the Artssponsors: Audrey Geisel/San Diego Foundation’s Dr. Seuss Fund, San Diego Foundation’s Isabella Fund,Sempra Energy, The Mandell Weiss Charitable Trust,The San Diego Foundation’s Weingart-Price Fund,Pfizer, Inc., and Merck Research Laboratories.

All the event proceeds will be used to defray thecosts associated with lending the auditorium, includingmaintenance, security, energy, and staff support.Through the “Performing Arts at The NeurosciencesInstitute” program, the Institute effectively saves SanDiego’s arts community more than $300,000 per year,by lending our facility for nearly 100 concerts annually.Over twenty thousand people attended events in theauditorium last year.

Gordon and Annika Kovtun, with Lael and Jay Kovtun,Honorary Chairs (left to right)

Event gathering with Theory Center in background

Jeff Enslin and Jennifer Satz, with Event Chair Linda Satz, and Joe Satz (left to right)

Educating the Community through our Library Roundtable Presentations

“Mainly Mozart is proud to have called the acousticallysuperb Auditorium at The Neurosciences Institute“home” since 1995. Dr. Gerald Edelman’s remarkablevision and passion for the arts has turned this localtreasure into one of the top concert halls in the region.The magnitude of The Neurosciences Institute’s gift toarts organizations and patrons over the past elevenyears is staggering. We at Mainly Mozart are profoundlyand eternally grateful.”

Nancy Laturno BojanicExecutive Director, Mainly Mozart

The Neurosciences Institute presents its own community lecture series, the Library Roundtable

program. It is offered several times each year at nocharge to the public. These lectures, delivered by leading figures in science and technology as well asother fields that pertain to neuroscience, are followedby a discussion session.

On November 16, Robert Malenka, M.D., Ph.D.,spoke about “Experience, Memory, and Addiction” at the latest presentation in the Library Roundtableseries. Dr. Malenka received his professional degreesfrom Stanford University and then completed a residency in psychiatry at Stanford. He is a worldleader in elucidating the mechanisms underlying theaction of neurotransmitters in the mammalian brainand in revealing the molecular mechanisms by whichneural circuits are reorganized by experience.

Dr. Malenka discussed the progress, to which hehas been a key contributor, over the last 25 years inunderstanding the mechanisms of neuronal communi-cation through synapses and of the adaptations insynaptic function that underlie all forms of normaland pathological behavior, such as addiction. Becauseof his training as both a cellular neurobiologist and aclinical psychiatrist, he has been at the forefront ofhelping to apply the knowledge gained from basicneuroscience research to the treatment and preventionof major psychiatric disorders. For information aboutour next Library Roundtable presentation, visit ourwebsite at www.nsi.edu.

Drs. Einar Gall, Robert Malenka, and Bill McColl

Miriam Goldberg and Jeanette Stevens

Daniel Hendrick at the piano, and the young and talented Elliott Wulff at the Minding the Arts Gala performance.


The results of the Institute’sresearch are made available

to the world-wide scientific com-munity by publication in variousmedia. The following items are asampling of recent work that maybe of particular interest to thegeneral public.

EDELMAN, G.M. (2006) SecondNature: Brain Science andHuman Knowledge, YaleUniversity Press.

This book offers a new theoryof knowledge based on strikingscientific findings about how thebrain works. It also addresses therelated question: Does the latestresearch imply that all knowledgecan be reduced to scientificdescription? Edelman’s brain-based approach to knowledge hasimplications for our understand-ing of the connections amongthe different ways we have ofknowing, as well as for dissolvingthe differences between scienceand the humanities. He foresees a day when brain-based deviceswill be conscious and reflects onthis and other fascinating ideasabout how we come to know theworld and ourselves.

DIERICK, H. AND R.J. GREENSPAN(2006) Molecular analysis offlies selected for aggressivebehavior. Nature Genetics38(9):1023-1031.

This study shows that flies can be made more aggressive byselective breeding, and it identifiesa gene likely to be involved infighting behavior. It represents animportant step in learning moreabout the gene networks underlyinga particular behavior.

IZHIKEVICH, E.M. (2006)Dynamical Systems inNeuroscience: The Geometryof Excitability and Bursting, MIT Press.

This book provides a compre-hensive introduction to nonlineardynamical systems theory anddescribes many novel applicationsof the theory to neuroscience. It is likely to become a key resourcefor advanced computational neuroscience courses in many universities worldwide.

MCKINSTRY, J.L., G.M. EDELMAN,AND J.L. KRICHMAR (2006) Acerebellar model for predictivemotor control tested in a brain-based device. Proceedings of theNational Academy of SciencesUSA 103(9):3387-3392.

This paper investigates theproposal that the cerebellum is a general purpose controller foradaptive control and motor learning.A model of the cerebellum basedon this principle was incorporatedinto a real-world brain-based device,which successfully learned to adaptits motor outputs to different cir-cumstances. The system describedmay be useful for developingintelligent machines.

DESAI, N.J. AND E.C. WALCOTT(2006) Synaptic bombardmentmodulates muscarinic effects inforelimb motor cortex. Journal of Neuroscience 26(8):2215-2226.

This paper examines the effectof complex synaptic backgroundactivity on how neuronal responseproperties are altered by the neuro-modulator acetylcholine. To do this,the authors made novel use of ahybrid methodology that combinesbiological recordings with computersimulations. The findings haveimportant general implications forthe study of other neuromodulatorsand drugs.

NITZ, D.A. (2006) Tracking routeprogression in the posterior parietal cortex. Neuron49(5):747-756.

This work’s importance lies inthe identification of a novel waythat spatial relationships in theworld are registered by brain activity.It appears that the parietal cortex is capable of assembling activity patterns which register the spatialrelationships between any arbitrarypair of objects or places.

SETH, A.K., E.M. IZHIKEVICH, G.N. REEKE, AND G.M. EDELMAN(2006) Theories and measures of consciousness: An extendedframework. Proceedings of theNational Academy of Sciences USA 103(28):10799-10804.

This paper distinguishes keyaspects of consciousness that can be measured. It then compares thestrengths and weaknesses of threequantitative measures of dynamicalcomplexity that have been appliedto consciousness: neural complexity,information integration, and causaldensity.

Selected Recent Publications

Hot Off the Press!

The Institute is committed to sharing the knowl-edge that we gain through our research with the

community at large. Aside from publishing articlesin scientific journals, we reach out to the publicthrough our Library Roundtable lecture series and by various presentations to community groups. We hold monthly educational lectures at Casa deMañana residence in La Jolla, and many of theInstitute’s Fellows frequently speak to various community groups about their latest research. Some of the recent presentations our fellows havemade include:n Dr. Jeffrey Krichmar, Senior Fellow in Theoretical

Neurobiology, gave a lecture on the technologyof brain-based devices at UCSD’s California StateSummer School for Mathematics & ScienceProgram (COSMOS). This program provides residential academic experience for gifted highschool students interested in careers in mathand science.

The Institute’s New WebsiteThe new design of The Neurosciences Institute’s website

(www.nsi.edu) premiered on September 30 in celebration of our25th anniversary. The new site offers a great deal of informationabout our scientific programs, campus architecture, and history. Our ongoing scientific research is presented in simplified summariesalong with downloadable files of our technical scientific reports. Inaddition, look for electronic copies of our BrainMatters newsletters,press releases, a schedule of performing arts and other upcomingevents at the Institute, and more. Please visit the website and findout about the many ways you can support the Institute’s programs.

n Dr. Aniruddh Patel, Esther J. Burnham SeniorFellow in Theoretical Neurobiology and anexpert in studies of music and the brain, presented a lecture for UCSD’s Grey Mattersseries, which has been broadcast by UCSD television. In addition, Patel has recently spoken about his research to the NationalAssociation of Teachers of Singing, theWednesday Club of San Diego, and the Osher Lifelong Learning group.

n In the series “Discussing the Mind and ItsComplexities” at Casa de Mañana, recentspeakers were Drs. Eugene Izhikevich, ElisabethWalcott, and Fred Jones. These short lectureshave become very popular with the residents,and they have been followed by lively discussionsabout topics such as computational models ofthe brain, cellular mechanisms of communication,and the effects of drugs like caffeine on the brain.

The Neurosciences Institute Reaching Out to the Community

www.nsi.edu

“Without the brain you can nothave sensation, perception, memory,consciousness, happiness, remorse,etc.,…and you wouldn’t be able toread a novel.” – Dr. Edelman

Deciphering how the brainworks in the state of health is thekey to understanding the processesthat lead to diseases like Parkinson’sand Alzheimer’s and for the devel-opment of potential treatments forsuch diseases. The outstandingresearch programs of TheNeurosciences Institute depend onthe financial support of individualsand private foundations. The

Institute has many opportunitiesfor donors to get involved. Forinformation about how to supportthe Institute and help advancebrain research, visit our website atwww.nsi.edu, or contact RachelJonte at [email protected], or 858-626-2018. All membership benefits arelisted on the website. Contributionsare tax-deductible to the extentallowed by law. The NeurosciencesInstitute is a nonprofit partnerwith the Endow San Diego programat The San Diego Foundation (seewww.endowsandiego.org).

On May 4, The Neurosciences Institute honored Lewis B. and Dorothy Cullman for

their invaluable support and visionary generosity.Mr. Cullman is Vice Chairman of the Institute’sBoard of Trustees. Mr. and Mrs. Cullman havedonated over $10 million to the Institute, largelythrough a challenge grant, that stimulatedanother $15 million in gifts from other donors.Their generosity has been recognized by namingRalph Greenspan and Joseph Gally as the LewisB. and Dorothy Cullman Senior Fellows.

The event honoring the Cullmans was heldat the newly renovated Museum of Modern Artin New York City, where the Cullmans are alsomajor benefactors. Many of the Institute’sTrustees and a number of community leadersattended the dinner, joining together to thankMr. and Mrs. Cullman for their combined imag-ination, foresight, generosity, and leadership.Dr. Edelman shared some of the Institute’s mainscientific accomplishments that were realized as a result of the Cullman’s support. The dinnerand festivities concluded with a song in tributeto Mr. and Mrs. Cullman.

Help Solve the Most Important Puzzle of Science:Become a Member of The Neurosciences Institute

Become a Member and Make a

Difference!

Friends..............................$250-999

Patrons.......................$1,000-4,999

Founders Circle....$5,000 and above

Celebrating the Generosity of

Lewis and DorothyCullman

Nerve Cell in Culture

From the Director

The celebration of the 25th

anniversary of theInstitute’s foundingprompted me to consider what haschanged and whathas remained constant over theyears. What has

remained unchanged includes our resolute commitment to understandinghow the human brain works and ourmode of organization as a scientificmonastery. What has changed most significantly is the flowering of new discoveries and the flood of new talentwhich it has been our good fortune to attract.

We remain committed to supporting nomore than forty remarkable young scientists inan atmosphere that encourages the sharpeningof critical research questions and the choice ofkey problems in brain science. We continue towelcome Visiting Fellows from a wide range offields to allow our young scientists to see acrosswider horizons. In this way, our interests remaindiverse, but not too diverse.

What has been achieved in the last twenty-five years? First, we have trained and cultivated 52former Fellows, who have gone on to distinguished,independent careers at research institutions hereand abroad. Second, we have made a series ofseminal discoveries ranging from innovation inembryonic brain transplants and the molecularbiology of sleep to a number of theoreticalachievements, culminating in the design for thefirst time of brain-based devices. These devicesprovide new ways of understanding brain actionand promise to open up new applications in thedesign of intelligent machines.

One might ask how our organizationalstructure prompts such discoveries. In part, theanswer rests in our style of funding research.Instead of judging a young person’s work by

how many grants he or she has obtained, weuse a larger set of more flexible criteria—choiceof problem, innovation, and, above all, imagi-nation. Of course, we expect skill to dominatethe design and execution of experiments, butbeyond skill we judge the marks of taste inanalyzing a problem and judgment in executingits solution.

Success in brain science (and in biology ingeneral) rests in picking the right example of a target for research. The great variety and complexity of animal systems cannot be examined by any one institution or approach.Unlike physics, where a general problem can beexpressed in mathematical form, the generalitiesof biology are best revealed by the inspiredchoice of animal species, tissues, and moleculesto serve as exemplars of deep principles. Ofcourse, as in physics, new methods and tech-nologies play a major role. We strive to keepabreast of such advances from day to day.

While experimentation is our foundation,we realize that studying the brain, which is perhaps the most complicated object in theknown universe, requires a global theoreticalapproach. We have steadfastly supported theorymaking and computer simulations of a varietyof key brain systems, and our Fellows havemade major contributions in this domain.

Clearly our efforts have grown and changedwith the passage of time. Over the years, wehave striven to make our work and facilitiesavailable to the community at large. We are particularly pleased by the response and supportof the San Diego community upon hearingabout our work. The philanthropic support ofthe community gives us a key impetus for ournext period of accomplishment.

In sum, what has changed over the lasttwo-and-a-half decades is the building of newconcepts of understanding the brain as the center of human concern. What has remainedconstant is our mode of organization along with our steadfast dedication to understandingthe human brain.

Gerald M. Edelman, M.D., Ph.D.Director

T H E P U B L I C A T I O N O F T H E N E U R O S C I E N C E S I N S T I T U T E

F a l l / W i n t e r 2 0 0 6Neurosciences Research Foundation, Inc.10640 John Jay Hopkins DriveSan Diego, CA 92121

ADDRESS SERVICE REQUESTED

Non-Profit Org

U.S.Postage

P A I D3373

San Diego, CA

BrainMatters

The Neurosciences Institute salutes Elisabeth “Jinx”Kenney Ecke, our long-time benefactor and dedicated

volunteer, for lighting the way to tomorrow through herinvolvement and investment in the Institute today. Jinxhas been serving on the Board of Trustees of the Institutesince 2002. She was instrumental in the planning and creation of our very first Minding the Arts gala event toraise funds for the Institute’s Performing Arts program.Her efforts have increased community awareness for thisimportant program, through which the Institute’sAuditorium is made available to local nonprofit organiza-tions at no charge for arts and culture events whichenhance the community of San Diego. Minding the Artswas so successful that it has become an annual event forfive years running, and Jinx remains actively involved on the Honorary Committee and as a sponsor.

A native of Bloomington, Indiana, and a graduate of San Diego State University, where she studied speechpathology, Jinx was married for 40 years to the late PaulEcke, Jr. of Ecke Poinsettia Ranch in Encinitas. She hasthree children and seven grandchildren. Jinx has beenvery active along with her family in promoting and supporting the California 4-H Youth DevelopmentProgram, which emphasizes citizenship, leadership, and life skills.

Jinx is an advocate of women’s civil rights andhas been a devoted supporter of Planned Parenthood,serving on their Board of Trustees for six years. Shehas been very active in helping to elect pro-choicecandidates to public office, and she is a foundingmember of the San Diego Women’s Foundation. Jinxcares deeply about children, arts, culture, and theenvironment, and she has funded many grants tolocal community organizations through her fund atThe San Diego Foundation. She has also been activelysupporting the San Diego Zoological Society. In 2005she was honored as the distinguished alumna of theyear by the San Diego State Alumni Association.Currently, she serves as Vice President of the Friendsof the Library at San Diego State University.

Jinx became involved as an advocate for theInstitute because she believes that its unique structure,leadership, capable scientists, and focus on fundamentalbrain research make it ideally positioned to makeimportant headway in understanding the mysterioushuman brain. She is excited about where this newunderstanding may lead in treating illness and disease. The Institute is deeply grateful for her dedication, generosity, and wisdom.

“Years ago when I was the leader of my daughter’s CampFire group, I came across this line in the leaders’ manual:‘Teach the girls to leave the campsite better than theyfound it.’ I’ve always thought of that as pretty goodadvice, and my involvement with The NeurosciencesInstitute is my attempt to do just that.”

“Light tomorrow with today!”

— Elizabeth Barrett Browning

DONOR PROFILE

Einar Gall, Jinx Ecke, and Gerald Edelman

the publication of the neurosciences institute

Documents