Targeted Gene Disruption in the CNS to Study Learning and Behavior
Until recently, the mouse was rarely used to study the biology of learning and memory. With advancements in gene-targeting technology, which now allow the structure and expression of a specific protein to be controlled in the intact animal, the mouse provides a powerful new tool to explore cognitive function. In mice, in contrast to other organisms, it is now possible to regulate the expression of a protein in the same neurons that are electrophysiologically and biochemically manipulable and are in a circuit involved in a defined learned behavior. Mouse mutants have been described that alter synaptic physiology, neuroanatomy, neurochemistry, and behavior. The mutants provide the first opportunity to correlate these phenotypes within animals engineered with defined molecular alterations. This review will discuss a range of methodologies that are required to describe the phenotype of mice with synaptic and behavioral abnormalities and focus on the interpretative difficulties of integrating these techniques.
Grant
SGN
Centre for Genome Research and Centre for Neuroscience, University of Edinburgh, West Mains Road, Edinburgh, EH9-3JQ, United Kingdom