Leadership In Controlled Gene Expression

Kandel and colleagues generated mouse lines, expressing tTA or rtTA, respectively, under the control of the CamKIIa promoter restricting tTA/rtTA expression to defined regions of the forebrain, particularly the hippocampus (Mayford et al., 1996, Mansuy et al., 1998a). Breeding these mice with another Tx mouse line expressing dominant negative versions of a CamKII or calcineurin (Mansuy et al., 1998b) under Tet-control, respectively, yielded double Tx animals to study synaptic plasticity. Kandel and colleagues showed that animals could not master a spatial learning task when the dominant negative version of the CamKIIa gene was expressed. However, animals which had first acquired the spatial learning program lost their memory after the dominant-negative proteins were induced. Surprisingly, these animals regained their spatial memory when the dominant proteins where turned off by supplying Dox in the drinking water. These data suggest that CamKIIa is not only required for learning and memory formation but also for the retrieval of information from memory.