WASHINGTON (July 25, 2014)—The link between autism and disrupted brain development is an essential part of the puzzle of the disease, and is largely unknown. However, thanks to funding from the Simons Foundation Autism Research Initiative (SFARI), George Washington University (GW) researcher Anthony-Samuel LaMantia, Ph.D. may be able to offer truly integrative and in-depth answers to these key questions in the field of autism research.
LaMantia, director of the GW Institute for Neuroscience and professor of pharmacology and physiology at the GW School of Medicine and Health Sciences (SMHS), was awarded $739K from SFARI for his promising research on a key class of nerve cells found in the cerebral cortex, which is the part of the brain that performs many key functions disrupted in autism, particularly social interaction, communication, and cognition.
SFARI is a leading funder of autism research in the U.S. The prestigious SFARI research grants support cutting edge research at several research institutions. The SFARI research grant received by LaMantia and colleagues is the first such award at GW.
LaMantia and his research team, which includes interdisciplinary collaborators from GW and the University of Pennsylvania School of Medicine, will first look at how these nerve cells are generated from cortical stem cells during prenatal development. They will then look at connections made between these nerve cells in one cortical area with nerve cells in other cortical areas. The connections between these nerve cells have been suggested to be either diminished or increased based on imaging studies in patients with autism spectrum disorders (ASD). There is no clear indication, however, what cortical neurons make the abnormal connections, and whether under- or over-connectivity is related to autism pathology.
“Everybody agrees that sometime during development, the way the cerebral cortex is wired gets disrupted in autistic patients and that this is a key reason for the difficulties in behavioral regulation that these patients encounter,” said LaMantia. “But no one really knows how that happens and what the end point is. We have the capacity to actually work out a key part of that question in a valid animal model.”
The research team has found a valid animal model with a genetic mutation highly associated with autism. Over the next three years, they will use a combination of genetic techniques that allow the developmental history of neurons in the cortex to be traced, anatomical techniques that allow the number of connections made by these neurons to be defined, and electrophysiological techniques that assess the capacity of these neurons to receive, process, and relay information. Critically, LaMantia and colleagues will also be able to evaluate behaviors related to autism in the same animals, giving insight into the relationship between development, connectivity, and behavioral pathology in ASD.
“This funding gives GW real credibility as an institution that is doing serious autism research,” said LaMantia. “We have a truly integrative group that can look at the developmental, cellular, biological, behavioral, and physiological issues of the question of under versus over connectivity — which remains a central issue in clinical ASD research — and how it arises during development. We are pleased to have the opportunity to answer these questions.”
Collaborators on this research include LaMantia, Thomas Maynard, Ph.D., associate research professor of pharmacology and physiology, Anastas Popratiloff, M.D., Ph.D., adjunct associate professor of anatomy and regenerative biology, both at GW SMHS, Lawrence Rothblat, Ph.D., professor of psychology and cognitive neuroscience at the GW Columbian College of Arts and Sciences, and Diego Contreras, M.D., Ph.D., professor of neuroscience at the University of Pennsylvania School of Medicine.
