Neuroscientists at Vanderbilt University are stepping into the national limelight with the establishment of a Silvio O. Conte Center for Neuroscience Research. The new center, funded by a $10 million grant from the National Institute of Mental Health (NIMH), will support interdisciplinary studies aimed at understanding the gene networks that control serotonin systems in the brain.
The neurotransmitter serotonin is central to brain biology: it participates in systems that control sleep, aggression, sexual drive, satiety, reward and mood. Serotonin has been implicated in a range of disorders including depression, obsessive-compulsive disorder, schizophrenia and autism, and medications that affect serotonin signaling, such as the SSRI (selective serotonin reuptake inhibitor) antidepressants, are widely prescribed.
The Vanderbilt Conte Center investigators are focusing their efforts on the raphe nuclei, a cluster of serotonin neurons that reside in the brain stem and receive input from and send messages to neurons throughout the rest of the brain.
“This is one of the most medically important cell groups in the nervous system, and the genes that control these neurons and their output are particularly key to our understanding of mental illness risk,” said Randy Blakely, Ph.D., director of the new Conte Center.
“Dr. Blakely has assembled the right team for the job of understanding how genetic variability affects neurotransmitter systems in the developing brain,” said Thomas Insel, M.D., director of the NIMH. “The new Center holds promise for hastening the day when discoveries in the lab will be translated into improved treatments for people with mental illnesses, from mood disorders to autism.”
Conte Centers for Neuroscience Research are a centerpiece of NIMH funding, said Beth-Anne Sieber, Ph.D., chief of the Developmental Biology Program at NIMH. “With these centers, NIMH is looking to the investigators to push their hypotheses forward, create new hypotheses, and find answers relevant to mental health.”
“The Vanderbilt center is the epitome of a Conte Center,” she said. “It really captures the spirit of integration and synergy between investigators.”
The centers are named for the late U.S. Rep. Silvio O. Conte, a longtime advocate for scientific research and organizer of the 1990s “Decade of the Brain” efforts. There are approximately 10 Conte Centers for Neuroscience Research and 10 Conte Centers for the Neuroscience of Mental Disorders — centers with a translational-clinical research emphasis.Blakely said the new center reflects Vanderbilt’s commitment to and investments in neuroscience programming, evident in the growth in research and education here over the last decade.
“This is a defining moment for the neurosciences at Vanderbilt,” said Jeffrey Balser, M.D., Ph.D., associate vice chancellor for Research. “Over the last few years, we have received several forms of external validation that affirm neuroscience at Vanderbilt has become absolutely top tier. An NIH Conte award makes that excellence even more visible to the national and international research community, and at the same time will provide crucial resources for making fundamental progress in mental health research.”
The Vanderbilt Conte Center includes scientists from the School of Medicine and the College of Arts and Science as well as researchers at other institutions. The center investigators will probe the workings of serotonin neurons in the raphe complex from their earliest stages of development to their function in mature animals. The operating hypothesis of the group, Blakely said, is that a rich network of genes establishes and maintains serotonin signaling in the brain and that deficits in the formation or stability of this network in humans underlies risk for mental illness.
The projects make extensive use of specialized mouse models, including mice in which serotonin neurons have been specifically tagged with fluorescent marker proteins or have had selective changes to their serotonin signaling molecules.
“We know that serotonin networks — broadly, all the genes that cooperate to control serotonin assembly and signaling — can be identified and manipulated in the mouse,” Blakely said, “and we feel strongly that the conservation of these networks in humans will allow us to formulate new hypotheses regarding disease-associated genetic variation.”
The Conte Center will also support multiple core facilities that “rest upon the significant technological framework that has been established at Vanderbilt through its shared resources program,” Blakely added.
In addition to its core facilities that will benefit the wider Vanderbilt research community, the Conte Center will administer a pilot grant program targeted to young investigators or established investigators who wish to enter the field of serotonin biology. The center will also host an annual symposium centered on the themes of the Conte program, and Conte Center members will participate in outreach activities that convey to a broader audience the “why” behind the research.
Vanderbilt Conte Center projects and leaders:
- Evan Deneris, Ph.D., Case Western Reserve University, “Genetic networks establishing serotonergic neuronal identity”
- Pat Levitt, Ph.D., Vanderbilt, “Serotonin modulation of axon guidance during brain development”
- Randy Blakely, Ph.D., Vanderbilt, “Signaling networks sustaining serotonin transport”
- Elaine Sanders-Bush, Ph.D., Vanderbilt, “Genetic variation of murine serotonergic phenotypes”
- Ronald Emeson, Ph.D., Vanderbilt, “Modulation and function of serotonin-2C receptors”
- Douglas McMahon, Ph.D., Vanderbilt, “Interactions of serotonin and circadian signaling networks”