DELTA：一种全脑突触蛋白转换测量方法揭示了学习过程中的局部可塑性，这一成果由霍华德休斯医学院Nelson Spruston小组经过不懈努力而取得。2025年3月31日出版的《自然—神经科学》杂志发表了这项成果。

在这里，该研究团队描述了一种新的方法，DELTA，以Janelia荧光染料和HaloTag敲入小鼠为基础，通过单突触分辨率绘制突触蛋白转换的全脑变化。在联想学习过程中，作为突触可塑性指标的嗜离子性谷氨酸受体亚基GluA2的周转量在大脑的几个区域，尤其是海马区CA1的周转量增加。在对环境富集的反应中，观察到更广泛分布的突触蛋白周转增加。在CA1中，GluA2的稳定性以特定的输入方式调节，与内嗅皮层相比，含有CA3输入的层的周转更多。DELTA将有助于探索学习和记忆的分子和电路基础，以及从单个突触到整个大脑的其他形式的可塑性。

据介绍，突触可塑性改变了神经元对经验的反应，这被认为是学习和记忆的基础。然而，与学习相关的突触可塑性的位点以及可塑性的定位或分布程度在很大程度上仍然未知。

附：英文原文

Title: DELTA: a method for brain-wide measurement of synaptic protein turnover reveals localized plasticity during learning

Author: Mohar, Boaz, Michel, Gabriela, Wang, Yi-Zhi, Hernandez, Veronica, Grimm, Jonathan B., Park, Jin-Yong, Patel, Ronak, Clarke, Morgan, Brown, Timothy A., Bergmann, Cornelius, Gebis, Kamil K., Wilen, Anika P., Liu, Bian, Johnson, Richard, Graves, Austin, Tchumatchenko, Tatjana, Savas, Jeffrey N., Fornasiero, Eugenio F., Huganir, Richard L., Tillberg, Paul W., Lavis, Luke D., Svoboda, Karel, Spruston, Nelson

Issue&Volume: 2025-03-31

Abstract: Synaptic plasticity alters neuronal connections in response to experience, which is thought to underlie learning and memory. However, the loci of learning-related synaptic plasticity, and the degree to which plasticity is localized or distributed, remain largely unknown. Here we describe a new method, DELTA, for mapping brain-wide changes in synaptic protein turnover with single-synapse resolution, based on Janelia Fluor dyes and HaloTag knock-in mice. During associative learning, the turnover of the ionotropic glutamate receptor subunit GluA2, an indicator of synaptic plasticity, was enhanced in several brain regions, most markedly hippocampal area CA1. More broadly distributed increases in the turnover of synaptic proteins were observed in response to environmental enrichment. In CA1, GluA2 stability was regulated in an input-specific manner, with more turnover in layers containing input from CA3 compared to entorhinal cortex. DELTA will facilitate exploration of the molecular and circuit basis of learning and memory and other forms of plasticity at scales ranging from single synapses to the entire brain.

DOI: 10.1038/s41593-025-01923-4

Source: https://www.nature.com/articles/s41593-025-01923-4