Mice in the Ivory Tower

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Focusing on 10 years of research carried out in mice, Yong-Seok Lee and Alcino Silva in a Nature Reviews Neuroscience article discuss how some mutations (and there are a surprising number of them) heighten cognitive function. Lee and Silva, from the Departments of Neurobiology, Psychology, Psychiatry and the Brain Research Institute at UCLA, call it “the beginning of a fundamental new approach in the study of enhanced cognition.”

The way the paradigm generally works: scientists mutate, delete or add to the mouse genomic milieu, then note the affect. The results, much of the time, are either unapparent or (as in the case of last week’s posting about ankyrins and muscles) deleterious.

Testing the intellect of a mouse requires its own level of higher thinking. Scientists have devised all sorts of exams to evaluate different aspects of learning and memory in mice. Aside from behavioral changes, like improved scores on maze tasks, most brainiac mice also show increased strength in connectivity between neurons, a phenomenon called long-term potentiation. Screening mice of many genetic backgrounds (i.e., lots of mutants) for high scores in nearly a dozen categories is revealing specific pathways pivotal to learning and memory.

While the research relies on intricate genetic manipulation that can be accomplished in the mouse, the authors believe the results could impact millions of people; people suffering from such disorders as autism, Alzheimer’s disease, schizophrenia and the list goes on. Lee and Silva argue that trying to find a treatment specific for each disorder is impractical. Honing in, however, on core molecular events that gate learning and memory is a promising strategy. Using available or finding new pharmacological agents to manipulate these key events is, in fact, underway.

Many of the mutations influence specific receptors involved with neurotransmitter binding and ion flow across cell membranes. The first mouse to gain attention for such ‘brilliance’ was reported 1998. Soon thereafter, a mouse dubbed doogie, after a child genius character in the TV drama Doogie Houser, M.D., acquired something akin to celebrity status. Lee and Silva compile a list of over 30 mutant mice with competing intellect that have been developed since.

The authors conclude with a tone of optimistic caution, acknowledging that such manipulations have the possibility of psychiatric/neurological backlash. Ultimately, however, they believe this approach has “tremendous potential.”

Perhaps in another 10 years, the doogie progeny will be authoring Today in Mice.

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