In vivo widefield calcium imaging of the mouse cortex for analysis of network connectivity in health and brain disease

Cramer, Julia V.; Gesierich, Benno; Roth, Stefan; Dichgans, Martin; Düring, Marco; Liesz, Arthur

doi:10.1016/j.neuroimage.2019.06.014

Cited by 62 publications

(52 citation statements)

References 57 publications

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“…In vivo widefield calcium imaging was performed as previously described in detail (83). In brief, as an optogenetic calcium-reporter mouse strain, C57BL/6J-Tg(Thy1-GCaMP6s)GP4.12Dkim/J (72) heterozygous mice were bred at the Institute for Stroke and Dementia Research, Munich.…”

Section: In Vivo Widefield Calcium Imagingmentioning

confidence: 99%

“…After 70 seconds, the animals were fixed in a stereotactic frame, the dose of isoflurane was decreased to 1.5% for 140 seconds and finally decreased to 0.75% for 4 minutes to maintain steadystate before data-acquisition. In vivo widefield calcium imaging was performed on a custom-built imaging setup described in (83). This setup allowed widefield imaging through the chronic window on top of the skull into the cortex of both forebrain hemispheres by covering a field-of-view of 12x12 mm, corresponding to an image matrix of 330x330 pixels.…”

Section: In Vivo Widefield Calcium Imagingmentioning

confidence: 99%

“…The videos were reviewed by an experienced rater and excluded when containing motion artifacts. To ensure intra-and interindividual correspondence of the analyzed cortical regions, preprocessed images from different acquisition blocks and animals were spatially co-registered, as previously described (83). In the registered images, the bregma was always located in the center of the image matrix and the sagittal suture corresponded to a vertical line.…”

Section: In Vivo Widefield Calcium Imagingmentioning

confidence: 99%

“…First, a general mask was applied to exclude lateral cortical areas, which were out of focus due to the curvature of the cortical surface as described in (83). Second, an individual mask was computed to exclude all pixels, in which the calcium signal was saturated due to autofluorescence, as occurring in areas affected by the infarct (83). Both, the general and the individual masks were combined for every acquisition.…”

Section: In Vivo Widefield Calcium Imagingmentioning

confidence: 99%

“…Both, the general and the individual masks were combined for every acquisition. To characterize changes in the cortical network after stroke, functional connectivity was computed between pairs of ROIs, representing functional cortical areas, previously defined (83). Functional connectivity was calculated as the Fisher z-transformed Pearson-moment correlation between the ROI signal time-courses.…”

Section: In Vivo Widefield Calcium Imagingmentioning

confidence: 99%

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Microglia monitor and protect neuronal function via specialized somatic purinergic junctions

Cserép

Pósfai

Orsolits

et al. 2019

Preprint

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Microglia are the main immune cells in the brain with emerging roles in brain homeostasis and neurological diseases, while mechanisms underlying microglia-neuron communication remain elusive. Here, we identify a novel site of interaction between neuronal cell bodies and microglial processes in mouse and human brain. Somatic microglia-neuron junctions possess specialized nanoarchitecture optimized for purinergic signaling. Activity of neuronal mitochondria is linked with microglial junction formation, which is rapidly induced in response to neuronal activation and blocked by inhibition of P2Y12-receptors (P2Y12R). Brain injury-induced changes at somatic junctions trigger P2Y12R-dependent microglial neuroprotection, regulating neuronal calcium load and functional connectivity. Collectively, our results suggest that microglial processes at these junctions are in ideal position to monitor and protect neuronal functions in both the healthy and injured brain.

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Section: In Vivo Widefield Calcium Imagingmentioning

confidence: 99%

Section: In Vivo Widefield Calcium Imagingmentioning

confidence: 99%

Section: In Vivo Widefield Calcium Imagingmentioning

confidence: 99%

Section: In Vivo Widefield Calcium Imagingmentioning

confidence: 99%

Section: In Vivo Widefield Calcium Imagingmentioning

confidence: 99%

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Microglia monitor and protect neuronal function via specialized somatic purinergic junctions

Cserép

Pósfai

Orsolits

et al. 2019

Preprint

Self Cite

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Nonparanormal graph quilting with applications to calcium imaging

Chang,

Zheng,

Dasarathy

et al. 2023

Stat

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Probabilistic graphical models have become an important unsupervised learning tool for detecting network structures for a variety of problems, including the estimation of functional neuronal connectivity from two‐photon calcium imaging data. However, in the context of calcium imaging, technological limitations only allow for partially overlapping layers of neurons in a brain region of interest to be jointly recorded. In this case, graph estimation for the full data requires inference for edge selection when many pairs of neurons have no simultaneous observations. This leads to the graph quilting problem, which seeks to estimate a graph in the presence of block‐missingness in the empirical covariance matrix. Solutions for the graph quilting problem have previously been studied for Gaussian graphical models; however, neural activity data from calcium imaging are often non‐Gaussian, thereby requiring a more flexible modelling approach. Thus, in our work, we study two approaches for nonparanormal graph quilting based on the Gaussian copula graphical model, namely, a maximum likelihood procedure and a low rank‐based framework. We provide theoretical guarantees on edge recovery for the former approach under similar conditions to those previously developed for the Gaussian setting, and we investigate the empirical performance of both methods using simulations as well as real data calcium imaging data. Our approaches yield more scientifically meaningful functional connectivity estimates compared to existing Gaussian graph quilting methods for this calcium imaging data set.

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