Miniature two-photon microscopy for enlarged field-of-view, multi-plane and long-term brain imaging

Zong, Weijian; Wu, Runlong; Chen, Shiyuan; Wu, Junjie; Wang, Hanbin; Zhao, Zhe; Chen, Guoqing; Tu, Rui; Wu, Danlei; Hu, Yanhui; Xu, Yangyang; Wang, Yao; Duan, Zhuoli; Wu, Haitao; Zhang, Yunfeng; Zhang, Jue; Wang, Aimin; Chen, Liangyi; Cheng, Heping

doi:10.1038/s41592-020-01024-z

Cited by 150 publications

(159 citation statements)

References 19 publications

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“…Thus, the gold electrode must be replaced by a transparent conductive material (i.e., graphene/indium tin oxide) in future studies. To study the activities of neurons of a free-moving mouse, a micro-scope was studied, as mentioned in the studies by Liberti et al (2017), Jacob et al (2018), and Zong et al (2021. The imaging in living and moving mouse was realized, but the recording of electrophysiology signals was still a challenge.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, some researchers devoted themselves to develop microscopes of lightweight and miniature volume for studying the behaviors of free-moving animals. For example, miniature two-photon microscopy (Zong et al, 2021), miniature microscopy for single-photon fluorescence imaging (Liberti et al, 2017), and compact head-mounted endoscopy (Jacob et al, 2018) have been developed. The miniscope is also a portable microimaging system consisting of a camera, an optical path system, and a detachable graduated refractive index (GRIN) lens.…”

Section: Introductionmentioning

confidence: 99%

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A Modified Miniscope System for Simultaneous Electrophysiology and Calcium Imaging in vivo

Yang

Song

et al. 2021

Front. Integr. Neurosci.

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The miniscope system is one of the calcium (Ca2+) imaging tools with small size and lightweight and can realize the deep-brain Ca2+ imaging not confined to the cerebral cortex. Combining Ca2+ imaging and electrophysiology recording has been an efficient method for extracting high temporal-spatial resolution signals in the brain. In this study, a particular electrode probe was developed and assembled on the imaging lens to modify the miniscope system. The electrode probe can be tightly integrated into the lens of the miniscope without increasing the volume, weight, and implantation complexity. In vivo tests verified that the proposed modified system has realized the simultaneous recording of Ca2+ signals and local field potential (LFP) signal in the hippocampus CA1 region of an adult mouse.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Modified Miniscope System for Simultaneous Electrophysiology and Calcium Imaging in vivo

Yang

Song

et al. 2021

Front. Integr. Neurosci.

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“…Due to the unsuitability of benchtop imaging for tasks that require unrestrained movement, investigators have tried, for almost two decades, to develop miniature 2P microscopes – 2P miniscopes – that integrate the 2P microscopés optical focusing and point-scanning components and can be carried on the head of freely moving animals. Portable devices that emerged from this work were connected to a remote stationary femtosecond laser source, photodetectors and acquisition equipment through cable assemblies containing optical fibers and electrical wires (Helmchen et al, 2013; Helmchen et al, 2001; Piyawattanametha et al, 2009; Sawinski et al, 2009; Zong et al, 2021; Zong et al, 2017). Early versions of these 2P miniscopes did not catch on, however, because they lacked the capacity to image sensitive calcium indicators such as GCaMP6, their scanning speed was slow, the miniscopes were heavy and difficult to carry for rodents, or optical cables were stiff and inflexible (Helmchen et al, 2001; Piyawattanametha et al, 2009; Sawinski et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

“…These constraints motivated attempts to develop a new generation of miniaturized 2P devices with resolution, speed and z -scanning capability comparable to that of 2P benchtop microscopes, and with a FOV close to that of 1P miniscopes (Li et al, 2021; Ozbay et al, 2018; Wallace and Kerr, 2019; Zong et al, 2021; Zong et al, 2017). Among these attempts were the 2P fiberscopes, where cable twisting and microscope weight were reduced by delivering fiber pulses and collecting fluorescence in a ‘double-claddinǵ fiber (Li et al, 2021; Rivera et al, 2011; Zhang et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Large-scale two-photon calcium imaging in freely moving mice

Zong

Obenhaus

Skytøen

et al. 2021

Preprint

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We developed a miniaturized two-photon microscope (MINI2P) for fast, high-resolution, multiplane calcium imaging of over 1,000 neurons at a time in freely moving mice. With a microscope weight below 3g and a highly flexible connection cable, MINI2P allowed imaging to proceed with no impediment of behavior in half-hour free-foraging trials compared to untethered, unimplanted animals. The improved cell yield was achieved through a new optical system design featuring an enlarged field of view (FOV) and a new micro-tunable lens with increased z-scanning range and speed that allowed for fast and stable imaging of multiple, interleaved planes as well as 3D functional imaging. A novel technique for successive imaging across multiple, adjacent FOVs enabled recordings from more than 10,000 neurons in the same animal. Large-scale proof-of-principle data were obtained from cell populations in visual cortex, medial entorhinal cortex, and hippocampus, revealing spatial tuning of cells in all areas, including visual cortex.

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“…Here we show results from imaging large areas of layers II/III of MEC and neighboring structures in mice using an upgraded version of the latest published miniaturized, portable two-photon microscopes (2P miniscopes) (Zong et al, 2017(Zong et al, , 2021. This upgrade shares critical features with the most recent version of the miniscope introduced in the accompanying Resource article in this issue (Zong et al).…”

Section: Introductionmentioning

confidence: 99%

Functional network topography of the medial entorhinal cortex

Obenhaus¹,

Zong²,

Jacobsen³

et al. 2021

Preprint

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The medial entorhinal cortex (MEC) creates a map of local space, based on the firing patterns of grid, head direction (HD), border, and object-vector (OV) cells. How these cell types are organized anatomically is debated. In-depth analysis of this question requires collection of precise anatomical and activity data across large populations of neurons during unrestrained behavior, which neither electrophysiological nor previous imaging methods fully afford. Here we examined the topographic arrangement of spatially modulated neurons in MEC and adjacent parasubiculum using miniaturized, portable two-photon microscopes, which allow mice to roam freely in open fields. Grid cells exhibited low levels of co-occurrence with OV cells and clustered anatomically, while border, HD and OV cells tended to intermingle. These data suggest that grid-cell networks might be largely distinct from those of border, HD and OV cells and that grid cells exhibit strong coupling among themselves but weaker links to other cell types.

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Miniature two-photon microscopy for enlarged field-of-view, multi-plane and long-term brain imaging

Cited by 150 publications

References 19 publications

A Modified Miniscope System for Simultaneous Electrophysiology and Calcium Imaging in vivo

A Modified Miniscope System for Simultaneous Electrophysiology and Calcium Imaging in vivo

Large-scale two-photon calcium imaging in freely moving mice

Functional network topography of the medial entorhinal cortex

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