Imaging spatial learning in the brain using immediate early genes: insights, opportunities and limitations

Immediate early gene (IEG) imaging offers a sophisticated approach to study the neural basis of learning in the brain. Demonstrating a high degree of spatial resolution, the activation of entire neuronal ensembles at multiple time-points can be observed. IEG imaging techniques have revealed a high level of responsiveness to spatial exploration within the hippocampus and other brain regions. The pattern of IEG activation is tightly linked with specific environments and appears to be involved in the subsequent consolidation of spatial information. This incidental learning is a potential confounding factor in studies investigating the neural correlates of spatial learning in both the radial arm maze and water maze. Although both these tasks increase hippocampal IEG expression from baseline levels, where control groups have fully explored the apparatus in the absence of task demands, or where animals are performing a non-spatial task, IEG expression in this region is comparable to spatially trained groups. However, the relationship between IEG expression and task performance, as well as the pattern of brain activation has been shown to differentiate between experimental and control groups. Inconsistencies between training protocols appear to contribute to the discrepancies between reported findings, and the role of IEG expression in the retention of spatial memory tasks remains unclear. Further investigation of the time course and dynamics of IEG expression during learning and retention is required to fully interpret observed results.