Precision Calcium Imaging of Dense Neural Populations via a Cell-Body-Targeted Calcium Indicator.,Neuron

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Precision Calcium Imaging of Dense Neural Populations via a Cell-Body-Targeted Calcium Indicator.
Neuron ( IF 16.2 ) Pub Date : 2020-06-26 , DOI: 10.1016/j.neuron.2020.05.029
Or A Shemesh ₁ , Changyang Linghu ₂ , Kiryl D Piatkevich ₃ , Daniel Goodwin ₄ , Orhan Tunc Celiker ₅ , Howard J Gritton ₆ , Michael F Romano ₆ , Ruixuan Gao ₇ , Chih-Chieh Jay Yu ₈ , Hua-An Tseng ₆ , Seth Bensussen ₆ , Sujatha Narayan ₉ , Chao-Tsung Yang ₉ , Limor Freifeld ₁₀ , Cody A Siciliano ₁₁ , Ishan Gupta ₁₂ , Joyce Wang ₁₃ , Nikita Pak ₁₄ , Young-Gyu Yoon ₁₅ , Jeremy F P Ullmann ₁₆ , Burcu Guner-Ataman ₁₇ , Habiba Noamany ₁₃ , Zoe R Sheinkopf ₁₈ , Won Min Park ₁₉ , Shoh Asano ₂₀ , Amy E Keating ₂₁ , James S Trimmer ₂₂ , Jacob Reimer ₂₃ , Andreas S Tolias ₂₄ , Mark F Bear ₁₃ , Kay M Tye ₂₅ , Xue Han ₆ , Misha B Ahrens ₉ , Edward S Boyden ₂₆

Affiliation

The MIT Media Laboratory, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA; Department of Biological Engineering, MIT, Cambridge, MA, USA; MIT Center for Neurobiological Engineering, MIT, Cambridge, MA, USA; Department of Brain and Cognitive Sciences, MIT, Cambridge, MA, USA; MIT McGovern Institute for Brain Research, MIT, Cambridge, MA, USA; Department of Neurobiology and Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
The MIT Media Laboratory, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA; MIT Center for Neurobiological Engineering, MIT, Cambridge, MA, USA; MIT McGovern Institute for Brain Research, MIT, Cambridge, MA, USA; Department of Electrical Engineering and Computer Science, MIT, Cambridge, MA, USA.
The MIT Media Laboratory, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA; Department of Biological Engineering, MIT, Cambridge, MA, USA; MIT Center for Neurobiological Engineering, MIT, Cambridge, MA, USA; Department of Brain and Cognitive Sciences, MIT, Cambridge, MA, USA; MIT McGovern Institute for Brain Research, MIT, Cambridge, MA, USA; School of Life Sciences, Westlake University, Hangzhou, Zhejiang Province, China.
The MIT Media Laboratory, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA; MIT Center for Neurobiological Engineering, MIT, Cambridge, MA, USA; MIT McGovern Institute for Brain Research, MIT, Cambridge, MA, USA.
MIT McGovern Institute for Brain Research, MIT, Cambridge, MA, USA; Department of Electrical Engineering and Computer Science, MIT, Cambridge, MA, USA.
Boston University, Department of Biomedical Engineering, Boston, MA 02215, USA.
The MIT Media Laboratory, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA; MIT McGovern Institute for Brain Research, MIT, Cambridge, MA, USA.
The MIT Media Laboratory, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA; Department of Biological Engineering, MIT, Cambridge, MA, USA; MIT McGovern Institute for Brain Research, MIT, Cambridge, MA, USA.
Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.
The MIT Media Laboratory, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA; MIT Center for Neurobiological Engineering, MIT, Cambridge, MA, USA; MIT McGovern Institute for Brain Research, MIT, Cambridge, MA, USA; Faculty of Biomedical Engineering, Technion, Haifa, Israel.
Vanderbilt Center for Addiction Research, Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA.
The MIT Media Laboratory, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA; Department of Biological Engineering, MIT, Cambridge, MA, USA; MIT Center for Neurobiological Engineering, MIT, Cambridge, MA, USA; MIT McGovern Institute for Brain Research, MIT, Cambridge, MA, USA.
The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, MIT, Cambridge, MA 02139, USA.
The MIT Media Laboratory, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA; MIT Center for Neurobiological Engineering, MIT, Cambridge, MA, USA; MIT McGovern Institute for Brain Research, MIT, Cambridge, MA, USA; Department of Mechanical Engineering, MIT, Cambridge, MA, USA.
The MIT Media Laboratory, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA; MIT Center for Neurobiological Engineering, MIT, Cambridge, MA, USA; MIT McGovern Institute for Brain Research, MIT, Cambridge, MA, USA; Department of Electrical Engineering and Computer Science, MIT, Cambridge, MA, USA; School of Electrical Engineering, KAIST Institute for Health Science and Technology, Daejeon, Republic of Korea.
Epilepsy Genetics Program, Department of Neurology, Boston Children's Hospital & Harvard Medical School, Boston, MA, USA.
The MIT Media Laboratory, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
The MIT Media Laboratory, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA; Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA.
Department of Biology, MIT, Cambridge, MA, USA.
Internal Medicine Research Unit, Pfizer, Cambridge, MA, USA.
Department of Biological Engineering, MIT, Cambridge, MA, USA; Department of Biology, MIT, Cambridge, MA, USA; Koch Institute, MIT, Cambridge, MA 02139, USA.
Department of Physiology and Membrane Biology, University of California, Davis School of Medicine, Davis, CA, USA.
Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA; Center for Neuroscience and AI, Baylor College of Medicine, Houston, TX, USA.
Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA; Center for Neuroscience and AI, Baylor College of Medicine, Houston, TX, USA; Department of Electrical and Computer Engineering, Rice University, Houston, TX, USA.
The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, MIT, Cambridge, MA 02139, USA; Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
The MIT Media Laboratory, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA; Department of Biological Engineering, MIT, Cambridge, MA, USA; MIT Center for Neurobiological Engineering, MIT, Cambridge, MA, USA; Department of Brain and Cognitive Sciences, MIT, Cambridge, MA, USA; MIT McGovern Institute for Brain Research, MIT, Cambridge, MA, USA; Koch Institute, MIT, Cambridge, MA 02139, USA.

Methods for one-photon fluorescent imaging of calcium dynamics can capture the activity of hundreds of neurons across large fields of view at a low equipment complexity and cost. In contrast to two-photon methods, however, one-photon methods suffer from higher levels of crosstalk from neuropil, resulting in a decreased signal-to-noise ratio and artifactual correlations of neural activity. We address this problem by engineering cell-body-targeted variants of the fluorescent calcium indicators GCaMP6f and GCaMP7f. We screened fusions of GCaMP to natural, as well as artificial, peptides and identified fusions that localized GCaMP to within 50 μm of the cell body of neurons in mice and larval zebrafish. One-photon imaging of soma-targeted GCaMP in dense neural circuits reported fewer artifactual spikes from neuropil, an increased signal-to-noise ratio, and decreased artifactual correlation across neurons. Thus, soma-targeting of fluorescent calcium indicators facilitates usage of simple, powerful, one-photon methods for imaging neural calcium dynamics.

中文翻译：

通过细胞体靶向钙指示剂对密集神经群体进行精确钙成像。

钙动力学的单光子荧光成像方法可以以较低的设备复杂性和成本捕获大视野中数百个神经元的活动。然而，与双光子方法相比，单光子方法受到来自神经纤维网的更高水平的串扰，导致信噪比降低和神经活动的人为相关性。我们通过设计荧光钙指示剂 GCaMP6f 和 GCaMP7f 的细胞体靶向变体来解决这个问题。我们筛选了 GCaMP 与天然和人工肽的融合，并确定了将 GCaMP 定位到小鼠和斑马鱼幼虫神经元细胞体 50 μm 内的融合。密集神经回路中以胞体为目标的 GCaMP 的单光子成像报告显示，来自神经纤维网的人为尖峰更少，信噪比增加，并减少神经元之间的人为相关性。因此，荧光钙指示剂的胞体靶向促进了使用简单、强大的单光子方法对神经钙动力学进行成像。

更新日期：2020-08-05

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