Memory and behavior: a second generation of genetically modified mice.

The use of standard genetic techniques, such as gene targeting and transgenesis, to study cognitive function in adult animals suffers from the limitations that the gene under study is often altered in many brain regions, and that this alteration is present during the entire developmental history of the animal. Furthermore, to relate cognitive defects to neuronal mechanisms of memory, studies have relied on examining long-term potentiation - an artificially induced form of synaptic plasticity. Recent technical advances allow the expression of a genetic alteration in mice to be restricted both anatomically and temporally, making possible a more precise examination of the role of various forms of synaptic plasticity, such as long-term potentiation and long-term depression, in memory formation. Recordings from so-called 'place cells' -hippocampal cells that encode spatial location -in freely moving, genetically modified mice have further advanced our understanding of how the actual cellular representation of space is influenced by genetic alterations that affect long-term potentiation.