近日，法国索邦大学教授Valentina Emiliani及其小组的最新研究揭示了使用体内双光子全息光遗传学和压缩传感的高通量突触连接映射。2025年9月17日，国际知名学术期刊《自然—神经科学》发表了这一成果。

该研究组提出了一个框架来提高映射吞吐量和速度，该框架结合了突触前神经元的双光子全息光遗传刺激，突触后反应的全细胞记录和稀疏连接的压缩感知重建。在连续的单细胞刺激下，该方法能够在麻醉小鼠的视觉皮层5分钟内快速探测多达100个潜在突触前细胞的连接情况，同时识别突触对及其强度和空间分布。

此外，在连接稀疏的种群中，全息多细胞刺激结合压缩感知方法进一步提高了采样效率，并恢复了与顺序方法相比发现的大多数连接，所需测量次数减少了三倍。总的来说，这些结果突出了更高通量体内电路分析和更深入地了解大脑结构-功能关系的潜力。

据了解，表征活神经回路中的突触连通性是理解行为过程中网络结构和功能之间相互作用的关键。然而，目前体内突触定位方法的吞吐量仍然非常有限。

附：英文原文

Title: High-throughput synaptic connectivity mapping using in vivo two-photon holographic optogenetics and compressive sensing

Author: Chen, I-Wen, Chan, Chung Yuen, Navarro, Phillip, de Sars, Vincent, Ronzitti, Emiliano, Oweiss, Karim, Tanese, Dimitrii, Emiliani, Valentina

Issue&Volume: 2025-09-17

Abstract: Characterizing synaptic connectivity in living neural circuits is key to understanding the interplay between network structure and function during behavior. However, the throughput of current in vivo synaptic mapping methods remains very limited. Here, we present a framework for increasing mapping throughput and speed that combines two-photon holographic optogenetic stimulation of presynaptic neurons, whole-cell recordings of postsynaptic responses and compressive sensing reconstruction of sparse connectivity. Under sequential single-cell stimulation, the method enables rapid probing of connectivity across up to 100 potential presynaptic cells within ~5min in the visual cortex of anesthetized mice, identifying synaptic pairs along with their strength and spatial distribution. Furthermore, in sparsely connected populations, holographic multi-cell stimulation combined with a compressive sensing approach further improved sampling efficiency and recovered most connections found using the sequential approach, with up to a threefold reduction in the number of required measurements. Overall, these results highlight the potential for higher throughput in vivo circuit analysis and deeper insights into brain structure–function relationships.

DOI: 10.1038/s41593-025-02024-y

Source: https://www.nature.com/articles/s41593-025-02024-y