Memory-specific temporal profiles of gene expression in the hippocampus

Abstract

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, they did not uncover the collective behaviors or patterns of the genes. We have used genome-scale screening to analyze gene expression during spatial learning of rats in the Morris water maze. Our results show distinct temporal gene expression profiles associated with learning and memory. Exogenous administration of one peptide whose sustained increase during memory retention was implicated by microarray analysis, fibroblast growth factor (FGF)-18, improved spatial learning behavior, suggesting that pharmacological modulation of pathways and targets identified may allow new therapeutic approaches for improving learning and memory. Results of this study also suggest that while learning and physical activity involve common groups of genes, the behavior of learning and memory emerges from unique patterns of gene expression across time.

Editing of the serotonin 2C receptor pre-mRNA: Effects of the Morris Water Maze

“…The MWM was chosen as a behavioral task because previous work by Cavallaro et al (2002) showed that it causes changes, that differ between the SC and WM mice, in the level of Htr2c mRNA during the 24 hours after the last exposure to swimming. Those experiments measured Htr2c mRNA levels in rat hippocampus by microarrays, and while not dramatic (the greatest was a four fold decrease), changes were significant.…”

“…Such changes were not replicated here in mice by quantitative RT-PCR, but there are reasonable explanations. First, the protocol for the MWM used here differed slightly from that of Cavallaro et al (2002), specifically in that we included a probe trial for all mice, after the three blocks of training. Thus, the time of euthanasia was delayed until after an additional swimming episode beyond the learning phase.…”

“…For SC mice, the platform was removed from the pool and "training" consisted of allowing them to swim for 60 seconds. The training protocol was similar to that of Cavallaro et al (2002). WM and SC mice received three blocks of training over two days.…”

“…Because exposure to the MWM has been shown to alter Htr2c mRNA levels in rats (Cavallaro et al 2002), and because stimulation/stress might induce transgene-related phenotypes not apparent in naive mice, we next tested for possible transgene effects in mice exposed to swimming only and exposed to swimming plus learning the location of a hidden platform. As shown in Figure 2, there were no significant differences in performance between wild type and either line of transgenic mice.…”

“…Nevertheless, the cumulative data suggest that HTR2C pre-mRNA editing is biologically relevant. Cavallaro et al (2002) classed the Htr2c as one of a number of "learning and memory genes" because transcript levels, as measured by microarray analysis, changed with time in rats exposed to the learning phase of the Morris Water Maze compared with those exposed to swimming alone. This observation prompts the question: do editing patterns change when transcript levels are dynamic and, if they do, how dynamic are the changes and are they relevant to learning?…”