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Picower researchers talk of mice and memory

Learning-disabled mice, disease-modeling flies, genes that boost brain power and ways to coax out new neurons in adults were among the topics presented at MIT's Picower Institute for Learning and Memory's annual retreat, held June 6-8 in Hyannis, Mass.

Keynote speaker Richard Morris of the University of Edinburgh's Laboratory for Cognitive Neuroscience described how he pushes the boundaries of animal behaviorial research to gain insights into the workings of the hippocampus, widely believed to play a critical role in learning and memory.

A member of the Picower visiting committee, Morris, a former experimental psychologist, devises studies that test whether mice have anything approaching the innate human ability to transport themselves mentally to another place and time. Probably not, he said, but they are able to develop a complex internal map of a chamber containing a buried treasure of enticing flavors: chocolate, coconut, cherry and banana among them. Then, prompted with a flavor, they can find which taste treat is buried where, and even determine with surprising speed where a new flavor is buried.

Morris also showed that if mice are presented with a novel experience--the ability to freely explore the test environment before they are put to work--they perform better at memory tasks. This may be related to the common human experience of remembering minute details of where we were and what we were doing when we experienced emotionally charged , dramatic events such as learning about the Sept. 11 terrorist attacks.

Morris said that in researchers' continuing quest to explain memory and the hippocampus, they are placing more emphasis on the specific roles of subregions within the tiny, seahorse-shaped brain area. "We're arriving at a point that some of the classical conceptions of the way the hippocampus is organized are in the process of being overturned," he said.

Among the 17 other talks and 40 poster presentations at the three-day event, Picower postdoctoral associate Bongjune Yoon described the use of peptides to block the synaptic weakening that occurs when neurons are deprived of stimuli; MIT biology graduate student Wyan-Ching Lee reported successfully creating mutant fruit flies that are a good model for Huntington's disease; Picower postdoctoral associate David Foster relayed the latest findings on what goes through the minds of rats that have just run a maze; and Picower postdoctoral associate Tadahiro Fujino described experiments showing that mice missing a certain gene displayed unusual learning impairments.

Carlos Lois, assistant professor of neuroscience in MIT's Department of Brain and Cognitive Sciences, described his laboratory's exploration of newly developing brain cells. The fact that neurons do not replace themselves in the adult forebrain is the main cause of symptoms and failed treatments for almost all neurodegenerative diseases, he said. "Mammals got the short end of the stick," he said, because other vertebrates, including reptiles and birds, are able to grow new brain cells in adulthood.

Yet it's not completely true that mammalian brains don't generate new cells. They do, but the undeveloped stem cells stay glued together in tightly packed clumps and don't migrate to where they might be needed to repair damaged tissue.

Only in the olfactory bulb and the hippocampus do newly formed brain cells have the ability to disperse. Lois has identified a growth factor that induces neuroblasts to migrate into the cortex and the striatum, holding out the hope that someday this may lead to a way to coerce adult stem cells in the brain to travel to areas that need repair, develop into full-fledged neurons and make connections among neighboring cells.

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