Expression of integrin-associated protein gene associated with memory formation in rats.

The present study has adopted the PCR differential display method to identify cDNA clones associated with memory formation in rats. The one-way inhibitory avoidance learning task was used as the behavioral paradigm. Total RNA isolated from the hippocampus of poor-memory (<80 sec) and good-memory (600 sec) rats 3 hr after training was used for comparison. Three cDNA fragments corresponding to different spliced forms of integrin-associated protein (IAP) mRNA were found to be differentially expressed in the hippocampus of good-memory rats. Quantitative reverse transcription-PCR revealed approximately four fold higher of IAP mRNA level in good-memory rats. This result was confirmed further by in situ hybridization analysis, and the major difference was in the dentate gyrus. It has been demonstrated that this difference in IAP mRNA expression is not attributable to different sensitivities of individual rats to electric shock. Rapid amplification of cDNA ends obtained the full-length IAP cDNA, which is 1192 bp in length excluding the poly(A+) tail. The IAP mRNA expression was significantly upregulated by NMDA and amphetamine injections to the dentate gyrus of the hippocampus. On the other hand, injection of antisense oligonucleotide complementary to the IAP transcript markedly impaired memory retention in rats and decreased the amplitude and slope of EPSP in the in vivo long-term potentiation paradigm. These results together suggest that IAP gene expression plays an important role in memory formation and synaptic plasticity in rat hippocampus.