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Minds Wide Open

Posted By craigc1 On March 22, 2012 @ 2:03 pm In Featured, Issue, Spring 2012 | No Comments

MINDOPEN-450In a suite of laboratories atop a gleaming glass-walled tower, researchers at Vanderbilt University Medical Center are designing radical new treatments for Parkinson’s disease, schizophrenia, and an inherited form of autism. A block away in a steel-shielded basement, children read aloud while their brains are being scanned in a doughnut-shaped MRI machine. This study of how the brain acquires language one day may benefit people with dyslexia and learning disabilities.

Vanderbilt has emerged as one of the nation’s leading academic centers in neuroscience, the study of the nervous system and the brain. By exploring how the brain perceives, decides, remembers and reacts, researchers are revealing how, in the words of Vanderbilt neuroscientist René Marois, “this piece of flesh could yield such a complex thing as the mind.”

Since 2000 the university has spent more than $60 million on neuroscience facilities, programs and faculty, while the amount in neuroscience grants awarded by the National Institutes of Health (NIH) has nearly doubled, reaching more than $44 million last year.

Vanderbilt’s neuroscience “community” today approaches 500 faculty members, students and staff in five schools and colleges, 22 departments, and 27 centers and institutes.

The commitment to bring neuroscience from the laboratory to the clinic, the operating room, the pharmacy and the classroom “is something that’s really important,” says Dr. Jeff Balser, MD’90, PhD’90, vice chancellor for health affairs and dean of the School of Medicine. “It should be an important part of our culture to do, because it moves our science and discoveries into the hands of the public.”

Vanderbilt’s approach is to invest in people, in cutting-edge facilities and technologies, and in a collegial atmosphere that encourages collaboration across far-flung disciplines, from biology, pharmacology and engineering to education, psychology and neurosurgery.

From the undergraduate level to the most advanced research, “our university’s commitment to research and training in neuroscience requires that we bring together our remarkable faculty from across campus to tackle the challenges of interdisciplinary research on brain and behavior,” says Vanderbilt Provost Richard McCarty. “Never has our ‘one university’ philosophy been more critical in advancing discovery in laboratories and training in the classroom.”

“The physical proximity of all the schools (everything is within a 15-minute walk from end to end) … allows for effortless interactions,” says Sohee Park, the Gertrude Conaway Vanderbilt Professor of Psychology and professor of psychiatry, whose work has helped define the cognitive deficits of schizophrenia.

Brain Matters

Among Vanderbilt researchers exploring the complex wiring of the brain, René Marois studies the neural bases of attention and information processing. His work has helped attract more pre-eminent scientists to Vanderbilt.

Among Vanderbilt researchers exploring the complex wiring of the brain, René Marois studies the neural bases of attention and information processing. His work has helped attract more pre-eminent scientists to Vanderbilt.

Vanderbilt engineers and neurosurgeons, for example, have joined forces to develop navigation systems that can guide the scalpel during brain operations. Neurosurgeons are partnering with chemists to develop fluorescent “labels” that can pinpoint the location of cancerous cells in the brain.

Working with neurologists and psychiatrists, neurosurgeons also are studying deep brain stimulation as a treatment for Parkinson’s disease and obsessive-compulsive disorder. The technique involves inserting a thin wire deep into the brain, then applying an electrical current.

“Hubs” of collaboration include the Vanderbilt Kennedy Center, the Vanderbilt Vision Research Center, the Center for Integrative and Cognitive Neuroscience, and the Vanderbilt University Institute of Imaging Sciences.

Coordinating many of these efforts is the Vanderbilt Brain Institute (VBI). The VBI links together “the enormously diverse and interdisciplinary community that is Vanderbilt neuroscience, with the ultimate goal of fostering the highest caliber of neuroscience discovery and training,” says VBI Director Mark Wallace, who is also a professor of hearing and speech sciences and professor of psychiatry.

Established in 1999 to promote neuroscience education and training as well as research, the VBI administers the Neuroscience Graduate Program, one of the leading programs of its kind in the country. Vanderbilt also sponsors a popular interdisciplinary neuroscience program for undergraduates that encourages students to participate directly in research.

Drug Discovery

P. Jeffrey Conn is director of the new Vanderbilt Center for Neuroscience Drug Discovery, which is creating new models for drug discovery at a time when pharmaceutical companies are investing less in research.

P. Jeffrey Conn is director of the new Vanderbilt Center for Neuroscience Drug Discovery, which is creating new models for drug discovery at a time when pharmaceutical companies are investing less in research.

Certainly, one of the most significant recent developments has been the establishment last year of the Vanderbilt Center for Neuroscience Drug Discovery, which supports and expands efforts to find novel treatments for brain disorders.

The center is directed by P. Jeffrey Conn, PhD’86, the Lee E. Limbird Professor of Pharmacology. Craig Lindsley, professor of pharmacology and chemistry, is the center’s director of medicinal chemistry as well as director of the Vanderbilt Specialized Chemistry Center.

Conn, Lindsley and their colleagues have developed compounds called “allosteric modulators” that can “tune” neurotransmitter receptors like dimmer switches in an electrical circuit—a departure from traditional drugs that “turn on” or “turn off” these receptors. The hope is that this more subtle approach will control symptoms better with fewer side effects.

Several compounds have shown promise in animal models of three different brain disorders.

Parkinson’s disease, a progressive disorder characterized by uncontrollable muscle tremors and rigidity, is caused by the death of dopamine-producing neurons in the brain. Dopamine replacement therapy can relieve symptoms, but over time it becomes less effective and causes debilitating side effects.

“We are very excited to reach this major milestone and are eager to fully understand the extent of benefit that this new treatment strategy will have in patients suffering from Parkinson’s disease”

—P. Jeffrey Conn

With support from NIH and the Michael J. Fox Foundation for Parkinson’s Research, Vanderbilt researchers are developing compounds that, by tuning a receptor for the neurotransmitter glutamate, may relieve the rigidity and “freezing” of certain muscles.

A second project seeks to improve treatment of schizophrenia. Current medications can reduce hallucinations and delusions, but they are less effective in relieving cognitive symptoms and social withdrawal. With funding from NIH and private industry, the researchers have identified compounds that work in two fundamentally different ways, and which they hope will alleviate all schizophrenia symptoms.

A third endeavor is raising hopes for the first drug treatment to relieve learning, memory, social and behavioral problems associated with fragile X syndrome, a genetic condition that shares features with autism.

Vanderbilt’s corporate partners are now completing animal tests of the schizophrenia and fragile X compounds required before they can be tried in humans. Early clinical trials could begin next year, Conn says.

“The combination of cutting-edge basic research in the context of an academic drug discovery program provides Vanderbilt with a tremendous capacity to both identify and treat complex brain disorders,” says Randy Blakely, the Allan D. Bass Chair in Pharmacology and a professor of psychiatry.

As they uncover the secrets that will lead to better drugs, Vanderbilt researchers are keenly aware that they stand on the shoulders of pioneering researchers. Vanderbilt neuroscience was built in part by psychopharmacologists who helped define—at the molecular level—the effects of drugs on the brain and nervous system.

They include Dr. Fridolin Sulser, professor of psychiatry and pharmacology, emeritus, who helped develop the tricyclic antidepressants; Elaine Sanders-Bush, PhD’67, professor of pharmacology, emerita, whose lab made several important discoveries about the neurotransmitter serotonin and its receptors; and Blakely, nationally known for his work on transporters, which sweep up neurotransmitters from the synaptic gap between nerve cells.

Blakely is program director of the Silvio O. Conte Neuroscience Research Center at Vanderbilt, established in 2007 with a $10 million grant from the National Institute of Mental Health, as well as the Vanderbilt Postdoctoral Training Program in Neurogenomics.

Early in his career, he discovered the genes for numerous transporters, including the serotonin transporter, target of the SSRI (selective serotonin reuptake inhibitor) antidepressants such as Prozac. Since then he and his colleagues have identified transporter gene variations that contribute to autism, depression, and attention deficit hyperactivity disorder.

Magnets in the Brain

John Gore’s 2002 arrival ushered in a new level of expertise in brain imaging for Vanderbilt. Gore brought along more than a dozen of his Yale colleagues to establish the Vanderbilt University Institute of Imaging Science.

John Gore’s 2002 arrival ushered in a new level of expertise in brain imaging for Vanderbilt. Gore brought along more than a dozen of his Yale colleagues to establish the Vanderbilt University Institute of Imaging Science.

As each area of neuroscience research grows and flourishes, it attracts top-level scientists in related fields. An example is Vanderbilt’s strength in functional magnetic resonance imaging, or fMRI. The technique measures changes in the magnetic properties of blood as it transports oxygen to brain tissue in response to increased activity. It can thus create “pictures” of brain areas that engage in reading, language and other cognitive functions.

As postdoctoral fellows at Yale University, Isabel Gauthier and her husband, René Marois, were “early adopters” of fMRI. In 1999 they joined the Department of Psychology in Vanderbilt’s College of Arts and Science—Gauthier to explore how the brain develops face-recognition “expertise,” and Marois to pursue the neural bases of attention and information processing.

Three years later one of their Yale mentors, John C. Gore, arrived with more than a dozen colleagues to establish and direct the Vanderbilt University Institute of Imaging Science. A leader in brain imaging since the late 1970s, Gore—the University Professor of Radiology and Radiological Sciences and Hertha Ramsey Cress Chair in Medicine—was among the first to use fMRI to evaluate reading disabilities in children.

The institute has become a “magnet” for other scientists, including Stephan Heckers, the William P. and Henry B. Test Chair in Schizophrenia Research. He arrived from the famed McLean Hospital in Boston in 2006 to chair Vanderbilt School of Medicine’s Department of Psychiatry and to continue his studies of the mechanism of psychosis.

“Neuroimaging has led us to realize that the major psychiatric illnesses are associated with structural brain changes,” says Associate Professor of Psychiatry Ronald Cowan, who directs the department’s Psychiatric Neuroimaging program. “The implication of this simple message for the diagnosis and treatment of mental illness is profound.”

For researchers like Peabody College’s Bruce McCandliss, the Patricia and Rodes Hart Professor of Psychology and Human Development, access to colleagues across the campus in neuroimaging and other disciplines is crucial. McCandliss is trying to identify educational interventions that can “reshape” the brain and bolster cognitive skills such as paying attention and reading.

“Vanderbilt has state-of-the-art neuroimaging facilities and a highly collaborative community, including Peabody College, which is leading the nation in research on education and human development,” he says. “This makes Vanderbilt an ideal place to bring these two strengths together into new research on educational neuroscience.”

The brain, as is now clear, is much more than networks of nerves and bursts of chemical and electrical energy. Thanks to recent advances in genetics, neuroimaging and computer science, researchers can track the complex wiring of the brain as never before.

It will take the concerted effort of many to understand how this remarkable organ regulates body temperature and circadian rhythms, controls movement, stores memories, acquires language and—perhaps most important—makes each individual unique.


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