One way to begin to understand the causes and effects of psychiatric illnesses is to examine the brain on the cellular level. More specifically, scientists look at how cells function on an individual level and how they interact with other cells in the brain. The Integrative Neurobiology Laboratory at McLean is dedicated exclusively to this approach.
Led by Chris Cowan, PhD, the lab is investigating the role that a function called “synaptic pruning” plays in disorders ranging from autism to substance use disorders. Synaptic pruning is an essential process in brain development by which certain neuron connections are eliminated so that others can strengthen.
Cowan’s team transferred to McLean from the University of Texas Southwestern Medical Center in 2012, and is the newest addition to the Center of Excellence in Basic Neuroscience. The recruitment was made possible by a generous gift from National Council members Stephen and Cathy Graham, who appreciate the importance of basic neuroscience in transforming how we treat disorders of the brain.
“There is tremendous potential in neuroscience today, and the best way to maximize discoveries is to engage the brightest researchers side-by-side where they can collaborate and work in the context of the problems they study,” Stephen Graham said. “McLean is an ideal place for that, and we are delighted to play a role in supporting Dr. Cowan.”
Synaptic Pruning – A Key to Brain Health
Neuroscience may be our best hope for understanding one of the most puzzling mental health issues of today—autism spectrum disorder (ASD), a developmental disability that causes varying degrees of social, communication, and behavioral challenges. ASD has become increasingly common in recent years, affecting one in every 88 children. Cowan and his team are investigating its causes.
A major clue, says Cowan, might be genetics. “When certain mutated genes are introduced to mice, the mice demonstrate behaviors that fit the diagnostic criteria for autism, including repetitive motor patterns, reductions in social interactions, and profound deficits in rodent language,” Cowan explained.
“Many of the genes implicated in ASD are involved in synapse function,” says Cowan. His studies have confirmed that rodents with autistic behaviors have too many synapses in their brains. His working theory is that without proper synapse pruning, the brain lacks the efficiency and specialization to master complex tasks like communication and social interaction.
The next question Cowan and his collaborators seek to answer is where exactly in the brain individual autistic behaviors arise. “If you can identify the cellular mechanism and its critical interacting partners, you can generate drug targets that could reverse symptoms,” said Cowan. He hopes that his work could someday lead to medication that effectively treats ASD.
Seeing the Big Picture
While the Integrative Neurobiology Lab focuses on microscopic elements that play a role in ASD, Cowan’s theories and approach are large scale. To understand ASD and many other illnesses, he said, we must consider both biological and environmental factors. Cowan explains brain development by likening it to the creation of a vessel on a potter’s wheel. If the potter’s fingers squeeze a little too tightly, there may be a subtle thinning on one section of the wall.
“If the pot is shipped across the country in a crate that’s not well padded, the vulnerable spot is weakened by the stress of travel, and the pot breaks,” explained Cowan. “I am interested in that intersection between environmental influences and underlying genetic vulnerability.”
To explore that intersection, Cowan’s lab is collaborating with fellow McLean researcher Bill Carlezon, PhD, who is interested in those external factors. Carlezon investigates how something like a viral infection contracted by a pregnant woman may contribute to her child’s later development of ASD.
The environment at McLean, which integrates clinical work, research, and education, is conducive to scientific discovery, said Cowan. “McLean offers a unique opportunity. I can look out my window and see a treatment center for substance abuse disorders and a school for individuals with autism spectrum disorders. It’s impossible for neuroscientists here to lose touch with what mental illness really means for patients,” explained Cowan. “Clinicians, clinical researchers, and basic neuroscientists here are working in synergy.”
The value that Cowan, in turn, brings to McLean is immeasurable. Joseph Coyle, MD, McLean’s chief scientific officer and chief of the Center of Excellence in Basic Neuroscience, said the hospital was very fortunate to attract a researcher of Cowan’s caliber and one who is also interested in nurturing the next generation of scientists.
“In a neuroscience program, you want your tool box to be full,” said Dr. Coyle. “At McLean, we have outstanding scientists specializing in molecular biology, electrophysiology, developmental neurobiology, and behavioral analysis. Dr. Cowan’s expertise in developmental molecular neurobiology enables him to see things that aren’t apparent—specifically, genes involved in autism and in addiction. He’s a very creative scientist, working at the leading edge of his field.”
The work of Cowan and the Center of Excellence in Basic Neuroscience plays an important role in the advancement of patient care, enhancing McLean’s capacity to improve lives.
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