Of Mice, Men and Molecular Neurobehavior

CINDY SANDERS
Posted: Wednesday, February 25, 2009 4:33 pm

Of Mice, Men and Molecular Neurobehavior | Ronald Emeson, neurobehavior, animal model, Vanderbilt University Medical Center, Vanderbilt Laboratory for Neurobehavior, mice, rats, genome, brain disorders

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Vanderbilt Opens Brain Disorders Research Lab

In mid-January, Vanderbilt University Medical Center opened a one-of-a-kind animal laboratory dedicated to the advancement of brain disorder research.

The 9,000 square feet of space devoted to the study of mouse and rat behavior is believed to be among the largest in academia. Situated on the ninth floor of the Vanderbilt Institute for Imaging Sciences, the Vanderbilt Laboratory for Neurobehavior represents more than two years of planning and design as researchers move to the next steps in understanding the complex role genes and genetic variation play on emotion, behavior, learning, attention and memory.

Ronald Emeson, PhD, is deputy director of the Vanderbilt Center for Molecular Neuroscience, which oversees the new research facility. He noted the completion of the human genome … followed closely by completion of mouse and rat genomes … represented a beginning for researchers rather than an endpoint.

"Just because we can identify all of the pieces, it doesn't mean we know what all the pieces do," he said. Like a disassembled bike, he continued, the individual parts are somewhat overwhelming when scattered across the floor. "It's not until it all gets assembled that you go, 'Oh, I see.'"

The hope is that the new lab will enable Vanderbilt researchers to have their own "ah ha" moments when it comes to a diverse spectrum of brain disorders including ADHD, autism, schizophrenia, Alzheimer's, addiction and obsessive-compulsive disorder, among others.

"Because we're looking at complex behavior, we want to use experimental model systems that are closer and closer to human beings," Emeson noted. "You can't do behavior in a tissue culture dish … complex behavior can't be seen in a single cell. You ultimately have to work at the whole animal level."

Although Vanderbilt has had a neurobehavior facility for about 10 years, Emeson said the former space had been retrofitted from previous animal rooms and was never ideal for the complicated world of studying animal behavior. Poor sound attenuation and venting led researchers to be concerned over how noises and smells impacted outcomes.

"We believed if we could design it from the ground up, we could design the perfect space... or the more nearly perfect space," Emeson said of the planning that went into the new facility.

The laboratory represents approximately $7 million in construction cost to house and study mice and rats. The university has also heavily invested in state-of-the-art equipment for measuring results in both species that will allow researchers to conduct more types of tests and with greater sensitivity. Emeson said the ongoing maintenance of the new space will be funded through the Center for Molecular Neuroscience, the Vanderbilt Kennedy Center for Research on Human Development and through a five year, $10 million Conte Center for Neuroscience Research grant from the National Institute of Mental Health.

"That may have been the final catalyst for making the whole thing come about," Emeson said of the NIMH funding. "The six investigators involved in the Conte Center all had mouse behavior as part of their research."

The new facility eliminates many variables that existed in the previous space.

"Of the $7 million spent, a large percentage of that was just on making sure the air flow was right," said Emeson. "In our previous facility, we had little control of that."

Proper ventilation and sound control also represented a significant portion of construction cost.

"Out in the wild, rats are predators for mice so there's a predator/prey relationship," Emeson explained. "Rats and mice rely on their sense of smell, which is very keen, so it's important they can't smell each other during measurements of their behavior."

He added that when mice are frightened or anxious, they give off specific pheromones and emit ultrasonic sound. "So now mice you haven't even tested yet are anxious because they're hearing and smelling others," Emeson said. He added that this problem has been eliminated in the setup of the new facility, which has sound-attenuated anterooms, testing rooms and a dedicated holding room. "Before they are moved into a room, the air is cleaned so there is no residual smell."

Grateful trainees also welcome the addition of the latest generation of video surveillance technology. Emeson said in the "old days," graduate students sat for hours and hours observing the animals and scoring behaviors. With the advent of video cameras, the students didn't have to physically sit in the room, but all the footage still had to be watched and scored.

"Now, we have the instrumentation so the computer actually recognizes certain movements and behaviors and can score itself," Emeson said.

Having the elaborately designed facility and highly sensitive instrumentation allows researchers to take their science even further.

"We have the ability to genetically modify mice … change individual letters in that genome … and then see how this changes behavior," Emeson said.

Although the research is being conducted on rodents, Emeson noted the many investigators using the new facility are aware that the end goal is to improve the quality of human health. Indeed, multiple animal models used in the facility carry genetic alterations found in humans with disorders such as autism or Alzheimer's Disease.

"Ultimately, we'd like to identify changes in gene structure and function that also influence human behavior and set risk for psychiatric disorders. You can't come up with treatments without knowing the targets. You have to know how the system works," he concluded.