Centripetal integration of past events by hippocampal astrocytes and its regulation by the locus coeruleus

Rupprecht, Peter; Lewis, Chris; Helmchen, Fritjof

doi:10.1101/2022.08.16.504030

Cited by 13 publications

(18 citation statements)

References 112 publications

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“…Moreover, we have not observed this aberrant phenomenon in transgenic thy1-GCaMP6s or 6f mice (JAX strain 025776 or 024276)(Masala et al . 2022; Rupprecht et al . 2023; Wenzel et al .…”

Section: Discussionmentioning

confidence: 99%

“…At University of Zurich: A more detailed procedure was described previously (Rupprecht et al . 2023).…”

Section: Methodsmentioning

confidence: 99%

“…At University of Zurich: A more detailed procedure was described previously (Rupprecht et al 2023). Briefly, mice (18 wks) were anesthetized using isoflurane (5% in O 2 for induction, 1-2%…”

Section: Virus Injectionsmentioning

confidence: 99%

“…At University of Zurich: A more detailed procedure was described previously (Rupprecht et al 2023). Briefly, 2 weeks after virus injection, the hippocampal window was implanted.…”

Section: Virus Injectionsmentioning

confidence: 99%

“…At University of Zurich: Neuronal population activity was recorded using a custom-built twophoton microscope (see Rupprecht et al 2023). Briefly light from a femtosecond-pulsed laser (MaiTai, Spectra physics; tuned to 960 nm; power below objective 40-45 mW) was used to scan the sample below a 16x objective (Nikon, water immersion, NA 0.8).…”

Section: Analysis Of Aberrant Ca 2+ Micro-wavesmentioning

confidence: 99%

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Aberrant hippocampal Ca²⁺micro-waves following synapsin-dependent adenoviral expression of Ca²⁺indicators

Masala,

Mittag,

Ambrad Giovannetti

et al. 2023

Preprint

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Genetically encoded calcium indicators (GECIs) such as GCaMP are an invaluable tool in neuroscience to monitor neuronal activity using optical imaging. The viral transduction of GECIs is commonly used to target expression to specific brain regions, can be conveniently used with any mouse strain of interest without the need for prior crossing with a GECI mouse line and avoids potential hazards due to the chronic expression of GECIs during development. A key requirement for monitoring neuronal activity with an indicator is that the indicator itself minimally affects activity. Here, using common adenoviral transduction procedures, we describe spatially confined aberrant Ca2+micro-waves slowly travelling through the hippocampus following expression of GCaMP6, GCaMP7 or R-CaMP1.07 driven by the synapsin promoter with AAV-dependent gene transfer. Ca2+micro-waves developed in hippocampal CA1 and CA3, but not dentate gyrus (DG) nor neocortex, were typically first observed at 4 weeks after viral transduction, and persisted up to at least 8 weeks. The phenomenon was robust, observed across laboratories with various experimenters and setups. Our results indicate that aberrant hippocampal Ca2+micro-waves depend on the viral titre of the GECI under the synapsin promoter. Further, neuronal subtype, and density of GECI expression may play a role. We used an alternative viral transduction method of GCaMP which avoids this artifact. The results show that commonly used syn-Ca2+-indicator AAV transduction procedures can produce artefactual Ca2+responses. Our aim is to raise awareness in the field of these artefactual transduction-induced Ca2+micro-waves and we provide a potential solution for this problem.Impact statement: Common adenoviral transduction procedures induce artefactual spatially confined Ca2+waves in the hippocampus.

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“…Moreover, we have not observed this aberrant phenomenon in transgenic thy1-GCaMP6s or 6f mice (JAX strain 025776 or 024276)(Masala et al . 2022; Rupprecht et al . 2023; Wenzel et al .…”

Section: Discussionmentioning

confidence: 99%

“…At University of Zurich: A more detailed procedure was described previously (Rupprecht et al . 2023).…”

Section: Methodsmentioning

confidence: 99%

Section: Virus Injectionsmentioning

confidence: 99%

“…At University of Zurich: A more detailed procedure was described previously (Rupprecht et al 2023). Briefly, 2 weeks after virus injection, the hippocampal window was implanted.…”

Section: Virus Injectionsmentioning

confidence: 99%

Section: Analysis Of Aberrant Ca 2+ Micro-wavesmentioning

confidence: 99%

See 3 more Smart Citations

Aberrant hippocampal Ca²⁺micro-waves following synapsin-dependent adenoviral expression of Ca²⁺indicators

Masala,

Mittag,

Ambrad Giovannetti

et al. 2023

Preprint

Self Cite

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Network-level encoding of local neurotransmitters in cortical astrocytes

Cahill,

Collard,

Tse

et al. 2024

Nature

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Astrocytes, the most abundant non-neuronal cell type in the mammalian brain, are crucial circuit components that respond to and modulate neuronal activity through calcium (Ca2+) signalling1–7. Astrocyte Ca2+ activity is highly heterogeneous and occurs across multiple spatiotemporal scales—from fast, subcellular activity3,4 to slow, synchronized activity across connected astrocyte networks8–10—to influence many processes5,7,11. However, the inputs that drive astrocyte network dynamics remain unclear. Here we used ex vivo and in vivo two-photon astrocyte imaging while mimicking neuronal neurotransmitter inputs at multiple spatiotemporal scales. We find that brief, subcellular inputs of GABA and glutamate lead to widespread, long-lasting astrocyte Ca2+ responses beyond an individual stimulated cell. Further, we find that a key subset of Ca2+ activity—propagative activity—differentiates astrocyte network responses to these two main neurotransmitters, and may influence responses to future inputs. Together, our results demonstrate that local, transient neurotransmitter inputs are encoded by broad cortical astrocyte networks over a minutes-long time course, contributing to accumulating evidence that substantial astrocyte–neuron communication occurs across slow, network-level spatiotemporal scales12–14. These findings will enable future studies to investigate the link between specific astrocyte Ca2+ activity and specific functional outputs, which could build a consistent framework for astrocytic modulation of neuronal activity.

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ASTRA: a deep learning algorithm for fast semantic segmentation of large-scale astrocytic networks

Bonato

Curreli

Romanzi

et al. 2023

Preprint

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Changes in the intracellular calcium concentration are a fundamental fingerprint of astrocytes, the main type of glial cell. Astrocyte calcium signals can be measured with two-photon microscopy, occur in anatomically restricted subcellular regions, and are coordinated across astrocytic networks. However, current analytical tools to identify the astrocytic subcellular regions where calcium signals occur are time-consuming and extensively rely on user-defined parameters. These limitations limit reproducibility and prevent scalability to large datasets and fields-of-view. Here, we present Astrocytic calcium Spatio-Temporal Rapid Analysis (ASTRA), a novel software combining deep learning with image feature engineering for fast and fully automated semantic segmentation of two-photon calcium imaging recordings of astrocytes. We applied ASTRA to several two-photon microscopy datasets and found that ASTRA performed rapid detection and segmentation of astrocytic cell somata and processes with performance close to that of human experts, outperformed state-of-the-art algorithms for the analysis of astrocytic and neuronal calcium data, and generalized across indicators and acquisition parameters. We also applied ASTRA to the first report of two-photon mesoscopic imaging of hundreds of astrocytes in awake mice, documenting large-scale redundant and synergistic interactions in extended astrocytic networks. ASTRA is a powerful tool enabling closed-loop and large-scale reproducible investigation of astrocytic morphology and function.

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Centripetal integration of past events by hippocampal astrocytes and its regulation by the locus coeruleus

Cited by 13 publications

References 112 publications

Aberrant hippocampal Ca²⁺micro-waves following synapsin-dependent adenoviral expression of Ca²⁺indicators

Aberrant hippocampal Ca²⁺micro-waves following synapsin-dependent adenoviral expression of Ca²⁺indicators

Network-level encoding of local neurotransmitters in cortical astrocytes

ASTRA: a deep learning algorithm for fast semantic segmentation of large-scale astrocytic networks

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Centripetal integration of past events by hippocampal astrocytes and its regulation by the locus coeruleus

Cited by 13 publications

References 112 publications

Aberrant hippocampal Ca2+micro-waves following synapsin-dependent adenoviral expression of Ca2+indicators

Aberrant hippocampal Ca2+micro-waves following synapsin-dependent adenoviral expression of Ca2+indicators

Network-level encoding of local neurotransmitters in cortical astrocytes

ASTRA: a deep learning algorithm for fast semantic segmentation of large-scale astrocytic networks

Contact Info

Product

Resources

About

Aberrant hippocampal Ca²⁺micro-waves following synapsin-dependent adenoviral expression of Ca²⁺indicators

Aberrant hippocampal Ca²⁺micro-waves following synapsin-dependent adenoviral expression of Ca²⁺indicators