Gavin Rumbaugh Explores the Workings of Memory

By Eric Sauter

When Gavin Rumbaugh, an assistant professor in the Scripps Research Institute Department of Neuroscience, was a senior in high school, the forward trajectory of his life came to a sudden halt.

He'd grown up on a dairy farm some 40 miles southeast of Pittsburgh, PA. The farm belonged to his grandfather, but his father had built a house in one corner of it, so Rumbaugh worked on the farm until he was 12. The work and his athletic bent made him, he said, the strongest kid in his school—and one of the better basketball players.

So good, in fact, that he was recruited in his junior year by the Air Force Academy to play basketball.

Then he hit a wall that he never even knew was there.

It turned out that Rumbaugh had Wolff-Parkinson-White syndrome, a rare birth defect that affects between one and three percent of the population. Those who suffer from it have an extra electrical pathway in the heart that results in tachycardia or rapid heartbeat. Though it can be a life-threatening condition in young males (Rumbaugh had assumed the episodes were something everybody felt), the syndrome can be treated through ablation, a catheter-based procedure that destroys the troublesome area of the heart.

"I got it fixed at the University of Pittsburgh," Rumbaugh said. "But the Air Force won't take anybody who has had a catheterization. If it wasn't for that, I would probably be working in aeronautics."

A New Path

The shock of it fundamentally altered his life, Rumbaugh said. Rather than the Air Force Academy in Colorado Springs, he found himself at a small school north of Pittsburgh—Westminster College—where he received a full scholarship to play basketball.

Rumbaugh, who was a biology major and chemistry minor, was still uncertain of what he was going to do after he graduated. His physiology professor offered a suggestion: if Rumbaugh didn't want to get a job, why not apply to graduate school? He took the graduate record exam in January of his senior year, did well, faxed off his applications, and got accepted at Georgetown.

Originally focused on cardiovascular medicine, he took a course in neuroscience his first year at Georgetown and ended up in the professor's laboratory. It took Rumbaugh just three and a half years to get his doctorate.

"As it turned out, I was pretty good at science," Rumbaugh said. "I graduated very fast, perhaps too fast. I did not deeply understand what I had learned in graduate school."

After four or five years of a postdoctoral fellowship at Johns Hopkins, Rumbaugh said he finally began to understand neurobiology on a level that he felt he should. That's when he got interested in synaptic plasticity and memory.

"Then I found a unique set of synaptic proteins and knew what I wanted to study," he said.

Moving Forward

After Rumbaugh finished his postdoctoral work at Johns Hopkins, he looked for a university where he could study how synaptic plasticity contributed to memory, which led him to a faculty position at the University of Alabama. It was also where he met his wife, Courtney Miller, who is also an assistant professor at Scripps Florida, in the Department of Metabolism and Aging. There was no hesitation whatsoever.

"Courtney was the very first person I saw when I got there," he said. "We were engaged five months later."

So, after some time spent finding his footing, Rumbaugh has settled into what has become a comfortable yet demanding professional and personal life at Scripps Florida, one where he can focus on memory formation, a very specific part of it.

"Your neurons fire when you experience something," he said. "Your brain encodes that experience through changes in many synapses—strengthening some, weakening others. We study how brain activity caused by learning can produce growth at individual synapses."

The synapse, the space separating individual neurons, is necessary for neurons to communicate; one neuron releases a neurotransmitter into the synapse that either activates or inhibits the other neuron. According to Rumbaugh, the growth of synapses is similar to the way a cell migrates, a process that involves actin, a major component of the cell cytoskeleton, and myosin, a protein involved in cell movement.

Actin is the substrate by which neurons grow, and synapses have one of the highest densities of actin anywhere. Myosin creates forces within these actin networks that can cause synapses to grow in one part of the brain or be destroyed in yet another.

"What my generation of neuroscientists is doing is trying to understand how actin is mobilized, because the changes in actin are key to synapse growth, which is a physical substrate of our memories," he said.

The Fight Against Aging

By the time humans reach their twenties, the number of synapses remains remarkably stable—if you learn something new, synapses grow, while others are degraded. This lasts until people reach their mid-forties. Then the number of synapses begins to decrease, first through aging and then often through various diseases of cognition such as Alzheimer's and Parkinson's diseases.

Rumbaugh wants to give those fading synapses a fighting chance, a way to cure or at least inhibit the loss that accompanies not only those diseases but aging itself.

Clinically, there's nothing available to actually help you learn or remember better, said Rumbaugh

"We know we can increase cognitive focus with drugs like methamphetamine, but those drugs don't work with Alzheimer's patients," he said. "We want to mechanically make information encoding and storage in the brain more efficient in an attempt to treat patients with memory disorders."

Common Links

Rumbaugh's work isn't focused entirely on myosin, actin, and synapse structure. The plasticity that allows humans to store memories, that strengthening and weakening of synapses, also occurs during brain development through molecular processes surprisingly similar to those of adult memory formation.

"When I came to myosin, I also found another protein that is critical to proper brain development—SynGAP," he said. "If you lose one copy of this gene, you will end up with Intellectual Disability (ID)."

As it turns out, SynGAP translates information from one neuron into biochemical impulses read by the next, directing signaling mechanisms far upstream from myosin, which, to Rumbaugh, indicates that SynGAP may, in fact, be essential to development of circuits that encode memories.

Right now, he's looking for a molecular link between SynGAP-mediated Intellectual Disability and other common forms mental retardation, such as Fragile X syndrome. He believes that dysfunction of myosin and actin may be a key pathological feature of neurodevelopmental disorders in general and would mark a convergence of his two major lines of research.

Which, in some ways, is very much how things have worked out for Rumbaugh—a convergence of the professional and personal in such a way that he seems to already know what is important and what isn't, what works and what doesn't.

"This is an all-consuming profession, and both Courtney and I have all-consuming careers," he said. "So we've had to work hard to figure out how to do it. We can be scientists and we can be husband and wife."

Rumbaugh loves to cook, for example, and the cooking is done through an interesting kind of teamwork: Miller invents dishes, and he figures out how to cook them. It puts everything in perspective, both family and career.

"Science may be all-consuming, but it has been very rewarding working at Scripps Research," he said. "Of course, you get setbacks; it's hard, but at the end of the day, I enjoy research and I have a great relationship, and that's what makes me happy."

Send comments to: mikaono[at]scripps.edu

"We study how brain activity caused by learning can produce growth at individual synapses," says Assistant Professor Gavin Rumbaugh. (Photo by James McEntee.)