美国霍华德休斯医学研究所Karel Svoboda、Loren L. Looger、Vivek Jayaraman等研究人员取得一项新突破。他们研究出了新的高性能钙离子传感器，用于神经元群体和细胞亚结构的活动成像。 这一研究成果于2019年7月发表在国际学术期刊《自然—方法学》上。

研究者利用蛋白结构变化导向的基因突变和基于神经元的筛选技术，优化了基于绿色荧光蛋白的钙离子探针-GCaMP6，以适应不同的活体成像模式。由此产生了jGCaMP7系列钙离子传感器：用于提高单个动作电位检测（jGCaMP7s, f），用于神经元轴突和神经毡成像的（jGCaMP7b），以及可能允许跟踪更多数量神经元活动的双光子成像(jGCaMP7s, f)或宽场成像(jGCaMP7c)。

据了解，利用基因编码钙离子探针进行钙成像通常用于测量完整神经系统的神经活动。GECIs经常用于两种不同模式中的一种:跟踪大量神经元胞体的活动，或跟踪亚细胞机构(如轴突、树突和单个突触室)的动态过程。尽管取得了重大进展，钙成像仍然受到现有GECIs的生物物理特性的限制，包括亲和力、信噪比、半衰期以及动态范围。

附：英文原文

Title: High-performance calcium sensors for imaging activity in neuronal populations and microcompartments

Author: Hod Dana, Yi Sun, Boaz Mohar, Brad K. Hulse, Aaron M. Kerlin, Jeremy P. Hasseman, Getahun Tsegaye, Arthur Tsang, Allan Wong, Ronak Patel, John J. Macklin, Yang Chen, Arthur Konnerth, Vivek Jayaraman, Loren L. Looger, Eric R. Schreiter, Karel Svoboda, Douglas S. Kim

Issue&Volume: Volume 16 Issue 7, July 2019

Abstract: Calcium imaging with genetically encoded calcium indicators (GECIs) is routinely used to measure neural activity in intact nervous systems. GECIs are frequently used in one of two different modes: to track activity in large populations of neuronal cell bodies, or to follow dynamics in subcellular compartments such as axons, dendrites and individual synaptic compartments. Despite major advances, calcium imaging is still limited by the biophysical properties of existing GECIs, including affinity, signal-to-noise ratio, rise and decay kinetics and dynamic range. Using structure-guided mutagenesis and neuron-based screening, we optimized the green fluorescent protein-based GECI GCaMP6 for different modes of in vivo imaging. The resulting jGCaMP7 sensors provide improved detection of individual spikes (jGCaMP7s,f), imaging in neurites and neuropil (jGCaMP7b), and may allow tracking larger populations of neurons using two-photon (jGCaMP7s,f) or wide-field (jGCaMP7c) imaging.

DOI: 10.1038/s41592-019-0435-6

Source:https://www.nature.com/articles/s41592-019-0435-6