Center for Neural Science, New York University, New York, New York 10003.
Applied Bioinformatics Laboratories, New York University Grossman School of Medicine, New York, New York 10016.
J Neurosci. 2021 Mar 24;41(12):2601-2614. doi: 10.1523/JNEUROSCI.1557-20.2021. Epub 2021 Feb 3.
A fundamental, evolutionarily conserved biological mechanism required for long-term memory formation is rapid induction of gene transcription upon learning in relevant brain areas. For episodic types of memories, two regions undergoing this transcription are the dorsal hippocampus (dHC) and prelimbic (PL) cortex. Whether and to what extent these regions regulate similar or distinct transcriptomic profiles upon learning remain to be understood. Here, we used RNA sequencing in the dHC and PL cortex of male rats to profile their transcriptomes in untrained conditions (baseline) and at 1 h and 6 d after inhibitory avoidance learning. We found that, of 33,713 transcripts, >14,000 were significantly expressed at baseline in both regions and ∼3000 were selectively enriched in each region. Gene Ontology biological pathway analyses indicated that commonly expressed pathways included synapse organization, regulation of membrane potential, and vesicle localization. The enriched pathways in the dHC were gliogenesis, axon development, and lipid modification, while in the PL cortex included vesicle localization and synaptic vesicle cycle. At 1 h after learning, 135 transcripts changed significantly in the dHC and 478 in the PL cortex; of these, only 34 were shared. Biological pathways most significantly regulated by learning in the dHC were protein dephosphorylation, glycogen and glucan metabolism, while in the PL cortex were axon development and axonogenesis. The transcriptome profiles returned to baseline by 6 d after training. Thus, a significant portion of dHC and PL cortex transcriptomic profiles is divergent, and their regulation upon learning is largely distinct and transient. Long-term episodic memory formation requires gene transcription in several brain regions, including the hippocampus and PFC. The comprehensive profiles of the dynamic mRNA changes that occur in these regions following learning are not well understood. Here, we performed RNA sequencing in the dorsal hippocampus and prelimbic cortex, a PFC subregion, at baseline, 1 h, and 6 d after episodic learning in rats. We found that, at baseline, dorsal hippocampus and prelimbic cortex differentially express a significant portion of mRNAs. Moreover, learning produces a transient regulation of region-specific profiles of mRNA, indicating that unique biological programs in different brain regions underlie memory formation.
长期记忆形成所必需的一个基本的、进化上保守的生物学机制是在相关脑区学习后快速诱导基因转录。对于情景类型的记忆，两个经历这种转录的区域是背侧海马体（dHC）和前额叶皮层（PL）。这些区域在学习后是否以及在多大程度上调节相似或不同的转录组谱仍有待了解。在这里，我们使用雄性大鼠背侧海马体和前额叶皮层的 RNA 测序来分析它们在未经训练条件下（基线）和抑制性回避学习后 1 小时和 6 天时的转录组。我们发现，在 33713 个转录本中，有超过 14000 个在两个区域中都在基线时显著表达，大约 3000 个在每个区域中被选择性富集。基因本体生物学途径分析表明，共同表达的途径包括突触组织、膜电位调节和囊泡定位。dHC 中富集的途径包括神经胶质发生、轴突发育和脂质修饰，而 PL 皮层中包括囊泡定位和突触小泡循环。学习后 1 小时，dHC 中有 135 个转录本显著变化，PL 皮层中有 478 个转录本显著变化；其中只有 34 个是共同的。学习对 dHC 中最显著调节的生物学途径是蛋白质去磷酸化、糖原和葡聚糖代谢，而在 PL 皮层中是轴突发育和轴突发生。训练后 6 天，转录组谱恢复到基线。因此，dHC 和 PL 皮层转录组谱的很大一部分是不同的，它们的学习调节在很大程度上是不同的和短暂的。长时情景记忆的形成需要包括海马体和 PFC 在内的几个脑区的基因转录。这些区域在学习后发生的动态 mRNA 变化的综合谱并不为人所知。在这里，我们在基线、学习后 1 小时和 6 天时，在大鼠的背侧海马体和前额叶皮层（PFC 的一个亚区）进行了 RNA 测序。我们发现，在基线时，背侧海马体和前额叶皮层差异表达了大量的 mRNAs。此外，学习产生了区域特异性 mRNA 谱的短暂调节，表明记忆形成依赖于不同脑区独特的生物学程序。
