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 9 publications

(13 citation statements)

References 112 publications

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“…4n). These propagative events may facilitate integration of information across cellular compartments which could allow for coordinated modulation of groups of nearby synapses 56 or spatiotemporal integration of inputs across individual cells 51 . Stimulation by glutamate consistently led to greater increases in propagative activity (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Since propagative response to a particular NT does not predict the response to the other NT nor to sequential stimulation by the same NT, we next looked for metrics that instead might predict astrocyte-network responses. Astrocyte Ca 2+ activity can depend on prior and current Ca 2+ levels 11,50,51 , which led us to ask whether network-level propagative responses could be predicted based on ongoing network activity. To do so, we asked whether the composition of baseline (1 min) activity in the network could predict the network-level response to uncaging (Extended Data Fig.…”

Section: Propagation Distinguishes Network Responsesmentioning

confidence: 99%

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Network-level encoding of local neurotransmitters in cortical astrocytes

Cahill,

Collard,

Tse

et al. 2023

Preprint

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Summary ParagraphAstrocytes—the most abundant non-neuronal cell type in the mammalian brain—are crucial circuit components that respond to and modulate neuronal activity via calcium (Ca2+) signaling1–8. Astrocyte Ca2+activity is highly heterogeneous and occurs across multiple spatiotemporal scales: from fast, subcellular activity3,4to slow, synchronized activity that travels across connected astrocyte networks9–11. Furthermore, astrocyte network activity has been shown to influence a wide range of processes5,8,12. While astrocyte network activity has important implications for neuronal circuit function, the inputs that drive astrocyte network dynamics remain unclear. Here we usedex vivoandin vivotwo-photon Ca2+imaging of astrocytes 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 events—differentiates astrocyte network responses to these two major neurotransmitters, and gates responses to future inputs. Together, our results demonstrate that local, transient neurotransmitter inputs are encoded by broad cortical astrocyte networks over the course of minutes, contributing to accumulating evidence across multiple model organisms that significant astrocyte-neuron communication occurs across slow, network-level spatiotemporal scales13–15. We anticipate that this study will be a starting point for future studies investigating the link between specific astrocyte Ca2+activity and specific astrocyte functional outputs, which could build a consistent framework for astrocytic modulation of neuronal activity.

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Section: Discussionmentioning

confidence: 99%

Section: Propagation Distinguishes Network Responsesmentioning

confidence: 99%

Network-level encoding of local neurotransmitters in cortical astrocytes

Cahill,

Collard,

Tse

et al. 2023

Preprint

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“…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 adeno-associated viral 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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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.

show abstract

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

Cited by 9 publications

References 112 publications

Network-level encoding of local neurotransmitters in cortical astrocytes

Network-level encoding of local neurotransmitters in cortical astrocytes

Aberrant hippocampal Ca²⁺micro-waves following synapsin-dependent adeno-associated viral expression of Ca²⁺indicators

Network-level encoding of local neurotransmitters in cortical astrocytes

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

Cited by 9 publications

References 112 publications

Network-level encoding of local neurotransmitters in cortical astrocytes

Network-level encoding of local neurotransmitters in cortical astrocytes

Aberrant hippocampal Ca2+micro-waves following synapsin-dependent adeno-associated viral expression of Ca2+indicators

Network-level encoding of local neurotransmitters in cortical astrocytes

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Aberrant hippocampal Ca²⁺micro-waves following synapsin-dependent adeno-associated viral expression of Ca²⁺indicators