The use of genetically engineered mice has been a major development in neuroscience research. Genetic engineering is an undoubtedly powerful technique; however, the value of this approach has been debated, particularly in relation to its use to probe the underlying bases of complex behaviors, such as memory. A recent new development of the technique is the ability to target a specific gene knockout to a particular subregion or even to specific and limited cell types of the mouse brain. An example of this approach is the knockout of the NMDARI gene in only CAI-pyramidal cells of the hippocampus. The resulting animals can be tested by several methods, including in vivo multielectrode recording during behavioral tasks. The data provide strong evidence in favor of the notion that NMDA receptor-dependent synaptic plasticity at CAI synapses is required for both the acquisition of spatial memory and the formation of normal CAI place fields. This relationship suggests that robust place fields may be essential for spatial memory.