Gene Expression profile during long-term memory consolidation

Changes in gene expression have been postulated to occur during long-term memory (LTM). We used high-density cDNAmicroarrays to assess changes in gene expression 24 h after rabbit eye blink conditioning. Paired animals were presented with a400 ms, 1000 Hz, 82 dB tone conditioned stimulus that coterminated with a 100 ms, 60 Hz, 2 mA electrical pulse unconditionedstimulus. Unpaired animals received the same conditioned and unconditioned stimuli but presented in an explicitly unpairedmanner. Differences in expression levels between paired and unpaired animals in the hippocampus and cerebellar lobule HVI,two regions activated during eye blink conditioning, indicated the involvement of novel genes as well as the participation ofpreviously implicated genes. Patterns of gene expression were validated by in situ hybridization. Surprisingly, the data suggestthat an underlying mechanism of LTM involves widespread decreased, rather than increased, gene expression. These resultsdemonstrate the feasibility and utility of a cDNA microarray system as a tool for dissecting the molecular mechanisms ofassociative memory.