August 30, 2012

Conte Center receives grant to study serotonin

The Silvio O. Conte Center for Neuroscience Research at Vanderbilt has received a $10.5 million federal grant to continue its groundbreaking research on serotonin signaling in the brain for another five years.

Randy Blakely, Ph.D

The Silvio O. Conte Center for Neuroscience Research at Vanderbilt has received a $10.5 million federal grant to continue its groundbreaking research on serotonin signaling in the brain for another five years.

The funding from the National Institute of Mental Health (NIMH), part of the National Institutes of Health (NIH), is not a renewal of the grant that established the center in 2007 but is a completely new award, officials said.

“NIMH wants to see that their center grants are scored on the basis of what you will do in the future, not what you did in the past,” explained Conte Center director Randy Blakely, Ph.D., the Allan D. Bass Professor of Pharmacology and Psychiatry at Vanderbilt.

The award will support four major studies in mouse models of how “perturbed” serotonin signaling during early development can have lifelong consequences on brain function and behavior.

“This center comprises a team of top investigators with a great track record of collaborations doing some of the most exciting and innovative work in the world in the area of serotonin in neuronal development,” said Chiiko Asanuma, Ph.D., program chief, Signal Transduction Program at NIMH.

“The new round of funding for this grant is a reflection of these investigators’ leadership in neuroscience research, education and outreach,” said Susan Wente, Ph.D., associate vice chancellor for Research and senior associate dean for Biomedical Sciences. “It is exciting to see their discoveries in model systems impacting our understanding of human brain function and disease.”

Serotonin is a neurotransmitter, or chemical messenger, that transmits signals between certain neurons — nerve cells — in the brain. It plays an important role in mood, sleep and cognition.

For example, antidepressants called selective serotonin reuptake inhibitors (SSRIs) are thought to elevate mood by increasing the supply of serotonin in the synapse, or gap between neurons. They do this by blocking serotonin transporters, which normally sweep serotonin out of the synapse between signals.

“Serotonin signaling is also one of the key determinants of whether early environmental stress will produce later-life mental illness,” Blakely said.

During the past five years, Conte Center investigators developed new mouse models that have already shed light on how serotonin neurons are born and differentiate, the role of peripheral serotonin in early brain development, how antidepressants act to alter behavior, and the role of serotonin in autism and Prader-Willi syndrome, two developmental disorders.

Last year Blakely and Conte Center co-investigators Pat Levitt, Ph.D., at the University of Southern California, and Evan Deneris, Ph.D., at Case Western Reserve University, jointly reported in the journal Nature that the placenta produces serotonin during a critical stage in fetal brain maturation.

The four major studies supported by the current Conte Center grant are led by:

  • Deneris, who is investigating epigenetic and environmental factors that may impact early decisions of serotonin-using neurons as they wire the brain;
  • Levitt, who will investigate how genes that control serotonin production in the placenta impact brain development and have enduring effects on behavior;
  • Blakely, who is studying how the serotonin transporter that is expressed in the immune system can lead to changes in immune function that can affect brain development and autism; and
  • Ron Emeson, Ph.D., the Joel G. Hardman Chair in Pharmacology at Vanderbilt, who is examining how changes in RNA of a specific serotonin receptor, the protein to which serotonin binds after crossing the synapse, can alter how the environment impacts brain function and behavior.

Other Conte Center investigators and their primary Vanderbilt departments are Paul Gresch, Ph.D., and Gregg Stanwood, Ph.D., (Pharmacology), Doug McMahon, Ph.D., (Biological Sciences), Jeremy Veenstra-VanderWeele, M.D., (Psychiatry) and Bing Zhang, Ph.D. (Biomedical Informatics).

Mark Wallace, Ph.D., director of the Vanderbilt Brain Institute and professor of Hearing and Speech Sciences, serves as the associate director of the Conte Center with responsibility for education and outreach.

Wallace helped lead development of an interactive “BrainMatters” exhibit, with funding from Vanderbilt’s original Conte Center grant. The interactive exhibit on brain science and research opened last year at Vanderbilt Health One Hundred Oaks.

The new grant will support a summer research program for undergraduates and provide parallel track training for graduate students in research and community outreach, Blakely said.

The awarding of the initial Conte Center grant also was an impetus for Vanderbilt University to fund construction of the Laboratory for Neurobehavior. The institutional core facility for behavioral assessments of rats and mice opened in 2009.

The Silvio O. Conte Center for Neuroscience Research at Vanderbilt is supported by NIH grant P50MH096972.