Dataset for the transcriptome analysis of hippocampal subfields identifies gene expression profiles associated with long-term active place avoidance memory

The hippocampus plays a critical role in storing and retrieving spatial
information. By targeting the dorsal hippocampus and manipulating specific
“candidate” molecules using pharmacological and genetic manipulations, we
have previously discovered that long-term active place avoidance memory
requires transient activation of particular molecules in dorsal
hippocampus. These molecules include amongst others, the persistent
kinases Ca-calmodulin kinase II (CaMKII) and the atypical protein kinase C
isoform PKC iota/lambda for acquisition of the conditioned behavior,
whereas persistent activation of the other atypical PKC, protein kinase M
zeta (PKM zeta) is necessary for maintaining the memory for at least a
month. It nonetheless remains unclear what other molecules and their
interactions maintain active place avoidance long-term memory, and the
candidate molecule approach is both impractical and inadequate to identify
new candidates since there are so many to survey. Here we use a
complementary approach to identify candidates by transcriptional profiling
of hippocampus subregions after formation of the long-term active place
avoidance memory. Interestingly, 24-h after conditioning and soon after
expressing memory retention, immediate early genes were upregulated in the
dentate gyrus but not Ammon’s horn of the memory expressing group. In
addition to determining what genes are differentially regulated during
memory maintenance, we performed an integrative, unbiased survey of the
genes with expression levels that covary with behavioral measures of
active place avoidance memory persistence. Gene Ontology analysis of the
most differentially expressed genes shows that active place avoidance
memory is associated with activation of transcription and synaptic
differentiation in dentate gyrus but not CA3 or CA1, whereas
hypothesis-driven candidate molecule analyses identified insignificant
changes in the expression of many LTP-associated molecules in the various
hippocampal subfields, nor did they covary with active place avoidance
memory expression, ruling out strong transcriptional regulation but not
translational regulation, which was not investigated. These findings and
the data set establish an unbiased resource to screen for molecules and
evaluate hypotheses for the molecular components of a
hippocampus-dependent, long-term active place avoidance memory.