脳回路を編集して記憶を強化するツールを開発(Scientists Engineer a Tool to “Edit” Brain Circuits and Enhance Memory)

ad

2026-04-15 韓国基礎科学研究院(IBS)

韓国基礎科学研究院(IBS)と韓国脳研究院の研究チームは、脳回路の構造を直接編集できる新技術「SynTrogo」を開発した。これはアストロサイトに特定シナプスを選択的に除去させる分子ツールで、神経活動を変えずに回路配線そのものを改変できる点が特徴である。マウス海馬での実験ではシナプス数が約27%減少した一方、残存シナプスは強化され、長期増強(LTP)が向上し、記憶力も改善した。さらに、この変化は可塑性を高め、学習後の応答性を強化することが示された。本成果は、シナプス数の単純な増加ではなく最適化が機能向上につながることを示し、自閉症やアルツハイマー病など回路異常疾患の新たな治療戦略や「コネクトーム編集」の基盤技術として期待される。

脳回路を編集して記憶を強化するツールを開発(Scientists Engineer a Tool to “Edit” Brain Circuits and Enhance Memory)
Figure 1. Synthetic Trogocytosis (SynTrogo) enables the “nibbling” of neuronal membranes by astrocytes through engineered ligand and receptor proteins. Upon SynTrogo induction, the synaptic density of the target CA3-CA1 hippocampal circuit was significantly reduced by ~27%. Conversely, the remaining synapses underwent structural and functional remodeling – characterized by the enlargement of pre- and post-synaptic compartments, enhanced long-term potentiation (LTP), and improved memory formation and retention.

<関連情報>

人工的に操作されたニューロンとアストロサイトの相互作用によるシナプス結合の再構築 Remodeling synaptic connections via engineered neuron-astrocyte interactions

Shin Heun Kim,Woojin Won,Gyu Hyun Kim,Yeon Hee Kook,Seungkyu Son,Songhee Choi,Dong Yeop Kang,Mingu Gordon Park,Young-Jin Choi,Seong Su Won,Juhee Shin,Yong Jeong,Kea Joo Lee,C. Justin Lee & Sangkyu Lee
Nature Communications  Published:15 April 2026
DOI:https://doi.org/10.1038/s41467-026-71440-w

Abstract

Information flow through synapses in the central nervous system is regulated by both rapid electrochemical activity and slower structural remodeling. While technological advances allow precise manipulation of synaptic activity, methods for structural remodeling remain limited. Here, we present SynTrogo (Synthetic Trogocytosis), a synthetic molecular approach for modulating synaptic connections. By engineering complementary ligand and receptor proteins, we enable physical interaction between two defined cell populations in culture, leading to a trogocytosis-like process in which receptor-expressing cells internalize membrane fragments and adjacent cytosolic material from ligand-expressing cells. Applying SynTrogo to hippocampal CA3 neurons and CA1 astrocytes in adult male mice results in ultrastructural changes at axon-astrocyte interfaces, accompanied by significantly reduced synaptic connectivity. The remaining synapses exhibit coordinated pre- and post-synaptic structural changes and reorganization of synaptic components and organelles, and are associated with enhanced synaptic plasticity and memory performance. These findings suggest that neural circuits can undergo adaptive reshaping under conditions of synaptic reduction and may provide a foundation for editing synaptic architecture with therapeutic potential for connectopathies.

細胞遺伝子工学
ad
ad
Follow
ad
タイトルとURLをコピーしました