Ca2+ imaging of neurons in freely moving rats with automatic post hoc histological identification

Anner, Philip; Passecker, Johannes; Klausberger, Thomas; Dorffner, Georg

doi:10.1016/j.jneumeth.2020.108765

Cited by 12 publications

(14 citation statements)

References 35 publications

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“…Although LiGS was developed for 3D histology, LiGS is also compatible with thin slices for multiplexed FISH labeling. LiGS slicing and imaging approaches can also improve the methodology presented by Anner et al (2020) for one-photon GRIN lens calcium imaging and cell reconstruction.…”

Section: Discussionmentioning

confidence: 99%

Light-guided sectioning for precise in situ localization and tissue interface analysis for brain-implanted optical fibers and GRIN lenses

et al. 2021

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Optical implants to control and monitor neuronal activity in vivo have become foundational tools of neuroscience. Standard two-dimensional histology of the implant location, however, often suffers from distortion and loss during tissue processing. To address that, we developed a three-dimensional post hoc histology method called ''light-guided sectioning'' (LiGS), which preserves the tissue with its optical implant in place and allows staining and clearing of a volume up to 500 mm in depth. We demonstrate the use of LiGS to determine the precise location of an optical fiber relative to a deep brain target and to investigate the implant-tissue interface. We show accurate cell registration of ex vivo histology with single-cell, two-photon calcium imaging, obtained through gradient refractive index (GRIN) lenses, and identify subpopulations based on immunohistochemistry. LiGS provides spatial information in experimental paradigms that use optical fibers and GRIN lenses and could help increase reproducibility through identification of fiber-to-target localization and molecular profiling.

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Section: Discussionmentioning

confidence: 99%

Light-guided sectioning for precise in situ localization and tissue interface analysis for brain-implanted optical fibers and GRIN lenses

et al. 2021

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“…In a full experiment with this type of data, singlecell and ensemble activity could be compared between different reinforcers and experimental phases to characterize the formation, maintenance, and recruitment of cells to specific ensembles. Importantly, while the use of calcium imaging is increasing, there are few published examples of calcium imaging at single-cell resolution in rats (Anner et al, 2020;Hart et al, 2020;Hornung et al, 2020), with fewer still using this technology to study addiction in rats (Cameron et al, 2019), and at present we were unable to find evidence of single-cell calcium imaging in rat deep brain structures. Thus, the data displayed here demonstrate the feasibility of using single-cell calcium imaging to record from a deep brain structure in rats, and add to a small knowledge base for using the technique to study addiction in rats.…”

Section: Utility For Understanding the Neurobiological Bases Of Addic...mentioning

confidence: 71%

Drug versus non‐drug behaviors: A dual‐reward model of sex differences and neurobiological mechanisms in rats

Nall

Chalhoub

Kalivas

2022

J Exper Analysis Behavior

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Substance Use Disorders (SUDs) are an impactful problem characterized by chronic relapse and engagement in drug‐related behaviors at the expense of non‐drug behaviors. Brain regions implicated in drug and non‐drug‐related behaviors often overlap, complicating investigations of neurobiological mechanisms underlying SUDs. Here we presented a within‐subject model for studying self‐administration, reinforcer competition, extinction, and cued reinstatement of cocaine‐ and food‐seeking in rats. Due to differences in cocaine‐ and food‐reinforced behavior, we transformed data to proportions of baseline, revealing increased resistance to extinction and disproportionately greater cued reinstatement of cocaine seeking relative to food seeking. Consistent with previous reports, females showed greater preference for cocaine reinforcement than males, though these findings failed to reach statistical significance. To demonstrate the model's utility for investigating neurobiological mechanisms, we included proof‐of‐concept calcium imaging data demonstrating the utility of the behavioral model for detecting cellular activity patterns associated with cocaine‐ and food‐seeking behaviors. Future studies utilizing this model should improve understanding of the development and expression of pathological behaviors characteristic of SUDs in humans, sex differences in these behaviors, and their neurobiological correlates. Thus, the model has utility for improving understanding of SUDs, leading to novel treatments to reduce the pathological behaviors associated with SUDs.

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“…To our knowledge, all reports of hippocampal in vivo calcium imaging have been done in mouse (although calcium imaging has been used to visualize other structures in rat (Scott et al, 2018;Anner et al, 2020;Hart et al, 2020;Pritchard et al, 2021)).…”

Section: Introductionmentioning

confidence: 99%

In VivoMulti-Day Calcium Imaging of CA1 Hippocampus in Freely Moving Rats Reveals a High Preponderance of Place Cells with Consistent Place Fields

Wirtshafter

Disterhoft

2022

J. Neurosci.

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Calcium imaging using GCaMP indicators and miniature microscopes has been used to image cellular populations during long timescales and in different task phases, as well as to determine neuronal circuit topology and organization. Because the hippocampus (HPC) is essential for tasks of memory, spatial navigation, and learning, calcium imaging of large populations of HPC neurons can provide new insight on cell changes over time during these tasks. All reported HPC in vivo calcium imaging experiments have been done in mouse. However, rats have many behavioral and physiological experimental advantages over mice. In this paper, we present the first (to our knowledge) in vivo calcium imaging from CA1 hippocampus in freely moving male rats.Using the UCLA Miniscope, we demonstrate that, in rat, hundreds of cells can be visualized and held across weeks. We show that calcium events in these cells are highly correlated with periods of movement, with few calcium events occurring during periods without movement. We additionally show that an extremely large percent of cells recorded during a navigational task are place cells (77.3±5.0%, surpassing the percent seen during mouse calcium imaging), and that these cells enable accurate decoding of animal position and can be held over days with consistant place fields in a consistent spatial map. A detailed protocol is included, and implications of these technological advancements are discussed. Significance statementIn vivo calcium imaging in freely moving animals allows the visualization of cellular activity across days. In this paper, we present the first in vivo Ca2+ recording from CA1 hippocampus in freely moving rats. We demonstrate that hundreds of cells can be visualized and held across weeks, and that calcium activity corresponds to periods of movement. We show that a high percentage (77.3±5.0%) of imaged cells are place cells, and that these place cells enable accurate decoding and can be held stably over days with little change in field location. Because the hippocampus is essential for many tasks involving memory, navigation, and learning, imaging of large populations of HPC neurons can shed new insight on cellular activity changes and organization..

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Ca2+ imaging of neurons in freely moving rats with automatic post hoc histological identification

Cited by 12 publications

References 35 publications

Light-guided sectioning for precise in situ localization and tissue interface analysis for brain-implanted optical fibers and GRIN lenses

Light-guided sectioning for precise in situ localization and tissue interface analysis for brain-implanted optical fibers and GRIN lenses

Drug versus non‐drug behaviors: A dual‐reward model of sex differences and neurobiological mechanisms in rats

In VivoMulti-Day Calcium Imaging of CA1 Hippocampus in Freely Moving Rats Reveals a High Preponderance of Place Cells with Consistent Place Fields

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