Changes in gene expression have been postulated to occur during long-term m
emory (LTM). We used high-density cDNA microarrays to assess changes in gen
e expression 24 h after rabbit eye blink conditioning. Paired animals were
presented with a 400 ms, 1000 Hz, 82 dB tone conditioned stimulus that cote
rminated with a 100 ms, 60 Hz, 2 mA electrical pulse unconditioned stimulus
. Unpaired animals received the same conditioned and unconditioned stimuli
but presented in an explicitly unpaired manner. Differences in expression l
evels 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 of previously
implicated genes. Patterns of gene expression were validated by in situ hyb
ridization. Surprisingly, the data suggest that an underlying mechanism of
LTM involves widespread decreased, rather than increased, gene expression.
These results demonstrate the feasibility and utility of a cDNA microarray
system as a tool for dissecting the molecular mechanisms of associative mem
ory.