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Of Mice and Memory
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| It’s difficult to know what mice remember, let alone how. But mice can and do tell us a great deal about memory — through neurogenetics. |
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With the help of his students, postdoctoral researchers, research associates, and hundreds of mice, Assistant Professor of Psychology Cliff Kentros is learning how the cells that relay information in the brain encode memories—by “eavesdropping” on these neurons in mice, recording their brain waves more than sixty times per second.
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| Assistant Professor Cliff Kentros believes his research can provide a window on the neural mechanisms of memory. |
“It’s like putting a bunch of microphones in there,” he says. “We hope to see what changes in that part of the brain while they learn something.”
Placed in new environments with asymmetrical cues on the walls, each mouse must learn how to turn off negative stimuli (bright lights and loud noises) by remembering the unmarked place that will do so. Kentros and his students use car alarm parts to create these mouse environments and thus have dubbed the new technique the “Brooklyn Maze.”
A former resident of New York City himself, Kentros has held research appointments at both the New York State Psychiatric Institute and Columbia University’s medical school. At Colum-bia, he worked with 2000 Nobel prizewinner Dr. Eric Kandel, who taught Kentros that the molecular basis of complex processes, such as learning, must first be considered in simpler systems.
“There’s more anatomical specificity in the brain than there is in all the rest of the body combined—by at least a factor of ten,” says Kentros, who taught neuro-anatomy at Columbia.
Kentros’ unique combination of scientific training in both cell and molecular biology and systems neurophysiology has led him to establish a UO lab in the Institute of Neuroscience that is equally unique. His lab is one of the few in the world that combines systems-level neuroscience with molecular biology.
We can start to work on molecules only after we’ve figured out the circuits, says Kentros. “It’s difficult to talk about how molecules affect a neural circuit before you understand what the circuit does.”
To do that, he and his research team, which includes collaborators at Rockefeller University and Cold Spring Harbor, genetically modify the neural circuits of mice. Their mice have “silencer” transgenes that can be “turned off” and “turned on” through the use of antibiotics. As a result, the scientists can see the before and after effects of silencing a defined part of the neural circuit.
Kentros draws sample circuits on the white board in his office, where his overarching questions are also writ large: Can rats imagine being somewhere? What are the neural processes we call attention?
“Understanding the basic process by which memories happen will, of course, give us new insight into how various pathological states occur at the cellular level,” says Kentros. “It’s these parts of the brain that go wrong in people with Alzheimers.”
Kentros’ research has relevance to clinical neuropsychiatry for its applications to studies of dementia, depression and neurological disorders such as ADHD and epilepsy. Though his research also has potential to reveal new knowledge about diabetes, drug abuse, alcoholism, strokes, and communication disorders, the clearest link is to dementia, the loss of memory and other cognitive functions in diseases like Alzheimers.
“If we lose memories of ourselves, we lose who we are,” says Kentros.
So what could Kentros’ studies reveal about memory loss? One answer to the question may come in the form of “non-performing” mice, those who fail to pay attention to the spatial cues of the task environment. Finding out what prevents them from making a stable representation of their environment could possibly tell us something about cognitive decline, Kentros says.
The University of Oregon has established a Mammalian Genetics Research Center (MGRC) to continue to explore these biological and psychological questions, and build upon its reputation as an institution that is at the forefront of attention and memory research. A key component of the MGRC is the Lewis Center for Neuroimaging, one of a handful of fMRI facilities located on a university campus without a medical center. Through the Brain, Biology, Machine Initiative, mouse researchers will share findings with colleagues who are simultaneously imaging human brain function, and will be able to easily compare data with the help of a huge computer network established to handle the vast amounts of biological information that their research generates.
Kentros, who has never worked outside of a medical school, says that it’s nice to be working at a research university like UO. He seems to enjoy working with the students who, he says, can get very creative in making the mouse environments. The latest is a black and white striped model. “It’s very avant garde,” he says with a smile.
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1245 University of Oregon • Eugene, OR • 97403-1245
(541) 346.3950 • FAX (541) 346.3282 • alumnidev@cas.uoregon.edu
Copyright © 2005 University of Oregon
Updated May 25, 2005
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