Late memory-related genes in the hippocampus revealed by RNA fingerprinting

Although long-term memory is thought to require a cellular program of gene expression and increased protein synthesis, the identity of proteins critical for associative memory is largely unknown. We used RNA fingerprinting to identify candidate memory-related genes (MRGs), which were up-regulated in the hippocampus of water maze-trained rats, a brain area that is critically involved in spatial learning. Two of the original 10 candidate genes implicated by RNA fingerprinting, the rat homolog of the ryanodine receptor type-2 and glutamate dehydrogenase (EC 1.4.1.3), were further investigated by Northern blot analysis, reverse transcription–PCR, and in situ hybridization and confirmed as MRGs with distinct temporal and regional expression. Successive RNA screening as illustrated here may help to reveal a spectrum of MRGs as they appear in distinct domains of memory storage.

尽管学界普遍认为长期记忆需要依赖基因表达的细胞程序以及蛋白质合成的增强，但对于关联记忆至关重要的蛋白质种类，目前仍知之甚少。我们采用RNA指纹图谱技术（RNA fingerprinting）筛选得到候选记忆相关基因（memory-related genes, MRGs），这些基因在水迷宫训练大鼠的海马体中表达上调；而海马体正是参与空间学习的关键脑区。经RNA指纹图谱技术筛选得到的10个候选基因中，有2个——即大鼠2型雷诺碱受体（ryanodine receptor type-2）同源基因与谷氨酸脱氢酶（glutamate dehydrogenase, EC 1.4.1.3）——通过Northern印迹杂交（Northern blot）、反转录PCR（reverse transcription–PCR）以及原位杂交（in situ hybridization）进行了进一步验证，最终确认其为具有独特时间与区域表达模式的记忆相关基因。如本研究所示，逐步递进的RNA筛选策略，或有助于揭示分布于记忆存储不同区域的一系列记忆相关基因。