The Role of Phosphorylated CREB in the Preferential Recruitment of Immature Dentate Granule Neurons into Learning and Memory Circuitry

Adult hippocampal neurogenesis has been linked with learning and memory in mammalian species (including humans). Recent work has demonstrated a critical period following the birth of new hippocampal neurons during which they display a competitive advantage over their neighbors and integrate preferentially into spatial memory circuitry. The current study represents a preliminary investigation into this effect, with the overarching goal of elucidating the molecular mechanism that underlies the accelerated integration of immature neurons into spatial memory circuitry. Based on its role in regulating both neurogenic processes (e.g., proliferation, maturation, and survival) and intrinsic neuronal excitability, it was hypothesized that the intracellular protein CREB might play an important role in the neurogenic basis of memory. To mark the birth of adult-generated neurons, rats were injected with the neural proliferation marker BrdU at several time-points (1, 3, 6, and 10 weeks) prior to training in the Morris Water Maze. Double-label (BrdU + pCREB) immunofluorescence in conjunction with high-powered confocal microscopy was used to visualize the extent of pCREB expression in both BrdU+ and BrdU- cells in the granule cell layer of the hippocampus. Three week old dentate granule neurons showed greater pCREB expression in response to the MWM than did their one week old counterparts. Although qualitative analysis indicates that pCREB is more strongly expressed in 6 week old dentate granule neurons relative to neighbouring neurons, this effect failed to reach statistical significance. Based on the small sample size used in the histological portion of this study in addition to the large effect size discovered, this failure to achieve statistical significance likely represents a type II error. That is, a significant effect is present, but the current study lacked the power to detect it statistically. The potential role played by CREB in mediating the preferential recruitment of immature neurons into hippocampal-dependent learning and memory circuitry warrants further investigation