Many experiments in the past have demonstrated the requirement of de novo gene expression during the long-term retention of learning and memory. Although previous studies implicated individual genes or genetic pathways in learning and memory, the collective behaviours of the genes is mostly unknown. We have used genome-scale screening by microarray analysis to examine the hippocampal expression of more than 1200 genes relevant to neurobiology during instrumental conditioning. Training rats on a step-through passive avoidance task led to unique patterns of gene expression when compared to naïve animals or those exposed to the conditioned or the unconditioned stimulus alone. The newly identified genes afford a quantitative view of the changes which accompany conditioning at the genomic level and enable deeper insights into the molecular basis underlying learning and memory.