大脳皮質の遠隔シナプスを変化させる「遠隔操作」の仕組みを解明(Remote-control in the cortex: How distant synapses are equipped for change)

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2026-09-30 マックス・プランク研究所

マックス・プランク脳研究所などの研究チームは、大脳皮質の最外層である「第1層」の遠位シナプスに、mRNAが局在し、そこでタンパク質が局所的に合成されていることを明らかにした。第1層は神経細胞体から遠く、従来、そのシナプスがどのように可塑的変化に必要なタンパク質を確保するのかが十分に分かっていなかった。研究ではレーザー捕捉微小切断、RNAシーケンス、蛍光in situハイブリダイゼーション、生化学的手法を組み合わせ、興奮性シナプスだけで1,000種類以上の局在mRNAを同定した。さらに、皮質第1層は海馬の遠位樹状突起を含む領域と分子構成が類似し、グリア細胞や細胞外マトリックスも共通することが判明した。これらの成果は、学習・知覚に関わるシナプス可塑性の分子機構や神経疾患の研究基盤となる。

大脳皮質の遠隔シナプスを変化させる「遠隔操作」の仕組みを解明(Remote-control in the cortex: How distant synapses are equipped for change)
Fluorescence microscopy image of cortical layer 1, highlighting the cellular architecture of this outermost cortical layer. Cell nuclei are shown in cyan, astrocytes in magenta, and neurons in green. (Scale bar = 20 microns) © MPI f. Brain Research/ T. Spanò

<関連情報>

皮質第1層における局所的なmRNAおよびタンパク質合成 Localized mRNAs and protein synthesis in cortical layer 1

Teresa Spanò ∙ Belquis Nassim-Assir ∙ Eva Kaulich ∙ … ∙ Lucija Marić ∙ Elena Ciirdaeva ∙ Erin M. Schuman
Cell Reports  Published:July 16, 2026
DOI:https://doi.org/10.1016/j.celrep.2026.117687

Highlights

  • Layer 1, its excitatory neuropil and its synapses actively synthesize new proteins
  • Large and distinct pools of mRNAs localize in layer 1 excitatory and inhibitory synapses
  • Layer 1 synapses have distinct transcriptomic profiles from deeper layer synapses
  • The layer 1 and hippocampal stratum lacunosum moleculare transcriptomes are markedly similar

Summary

Cortical layer 1 plays an essential role in neural networks, integrating many streams of information and undergoing plasticity during learning. Yet, we know little about the underlying molecular processes and whether layer-specific adaptations exist. Here, we show that layer 1 and its synapses actively synthesize proteins. Using laser capture RNA-sequencing and fluorescence in situ hybridization, we report an abundance of localized synaptic transcripts. We purify layer 1 excitatory and inhibitory mouse synapses and characterize their enriched transcriptomes, identifying proteins that can be locally synthesized and finding significant differences with deeper layer transcriptomes. Finally, we discover a strong similarity between cortical layer 1 and hippocampal stratum lacunosum moleculare, which suggests a conserved molecular architecture of these distal layers. Together, our results establish local protein synthesis as an important feature of cortical layer 1, and we provide the first comprehensive description of the transcriptomes of layer 1 and its synapses, which we make available online.

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