Watching Mice Think

Karel Svoboda at the Cold Spring Harbor Laboratories on Long Island is doing something no one else has ever done before. He is watching how mice think. He doesnt sit and watch a mouse in a maze with a puzzled expression on its face no, he watches the brain of a mouse react to new experiences. How does he do this? With GFP of course. Joshua Sanes, a collaborator of his from the Washington University School of Medicine in St. Louis, created a transgenic mouse strain that expresses GFP in some of the neurons in the cortex. Then together with some of his students and collaborators, Svoboda has replaced sections of the skulls of these transgenic young mice with transparent windows, so that they can watch what happens to the region of their cortices, which processes sensory information derived from their whiskers. The mice can live out their entire lives with the windows in place, allowing Svoboda the opportunity to monitor the changes occurring over many weeks. He observed tiny spines along the dendrites rising and receding. The rate of spine turnover increased as the mice were exposed to new experiences. The figure below shows YFP and GFP labeled cerebral neurons in two lines of transgenically modified mice. Karel is now continuing his work at the HHMI Janelia Farm.

 Fluorescent protein expression in the cerebral neurons in two different lines of transgenic mice. In the one line, GFP is expressed sparsely; in the other YFP is expressed abundantly. Both pictures were taken through a glass window embedded in live mice. (Photocredit: Brian Chen and Karel Svoboda, Howard Hughes Medical Institute, Cold Spring Harbor Laboratory)

Using similar methods Kuan Hong Wang, a researcher at MIT’s Picower Institute for Learning and Memory, was able to monitor protein expression in the primary visual cortex of living mice. He and his co-workers labeled a protein named, ARC, which acts as a molecular filter enhancing the brains ability to respond to visual stimuli. In a study reported in Cell 2006, 126, pg. 329 they examined the expression of ARC in the brain of mice that were exposed to cylinders with vertical and horizontal stripes. They found that if they repeatedly exposed the infant mice to the same visual stimulus the amount of ARC produced decreased. The Arc protein was training the brain to interpret the visual signals. One of the ways it does this is by blocking the activity of less efficient neurons.