| 研究実績の概要 |
The proposed studies examined possible mechanisms underlying memory consolidation in sleep. More specifically, we investigated the role that protein kinase A (PKA) activation in sleep may play in the consolidation of fear memory. Animals were fear conditioned and allowed to sleep or were kept awake for 4h immediately following conditioning. Upon entering sleep, they were injected intra-hippocampally with the PKA inhibitor Rp-cAMPs or vehicle control. Animals were retested for fear memory 24h later. We observed that PKA inhibition suppressed long-term fear memory. In a subgroup of animals that were kept awake following fear conditioning, intra-hippocampal injection of the PKA activator Sp-cAMPs rescued the sleep-deprivation induced memory disruption (Cho, et al. 2018). In a second set of experiments, we investigated the role that sharp-wave ripples (SPWr; observed in hippocampal EEG during slow wave sleep) may play in fear memory consolidation and whether SPWr may induce their effects via activation of PKA or Epac (a cAMP downstream protein). SPWr elimination (with electrical stimulation of hippocampal afferents) during sleep produced a significant fear memory deficit at 24h retest. Further, SPWr elimination produced a suppression of phosphorylated PKA and Epac in the dorsal hippocampus. We are currently finalizing this study by injecting Sp-cAMPs in the hippocampus in SPWr suppressed animals to determine whether PKA replacement may rescue the SPWr suppression of fear memory.
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