Centripetal integration of past events in hippocampal astrocytes regulated by locus coeruleus

Rupprecht, Peter; Duss, Sian N.; Becker, Denise; Lewis, Christopher M.; Bohacek, Johannes; Helmchen, Fritjof

doi:10.1038/s41593-024-01612-8

Cited by 11 publications

(1 citation statement)

References 78 publications

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“…In evaluating the role of astrocytes in the NVC response to auditory activation, large astrocytic Ca2+ elevations seen during mouse movements/arousals are likely confounding factors. According to recent data, they would rather be involved in associating brain states (Reitman et al, 2023) or in integrating past events (Rupprecht et al, 2024), which makes them irrelevant in the initiation of NVC. Therefore, we decided to focus our investigations on dilations and astrocyte Ca2+ elevations occurring during the animals’ resting periods.…”

Section: Resultsmentioning

confidence: 99%

Fast 3D imaging in the auditory cortex of awake mice reveals that astrocytes control neurovascular coupling responses locally at arteriole-capillary junctions

Lind,

Volterra

2024

Preprint

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During neuronal activity, cerebral blood flow increases to ensure adequate glucose and oxygen supply, a crucial mechanism known as the neurovascular coupling response. Blood is drawn from the brain’s surface through penetrating arterioles (PA) and locally redistributed via branching capillaries in the cerebral cortex. All blood vessels, regardless of cortical layer or size, are covered by astrocytic end-feet, suggesting a potential regulatory role. Though the regulatory machinery is known to be present in astrocyte end-feet, its role in this blood recruitment is still controversial. A likely explanation for the controversy is that studies so far have been done without considering the structural basis for blood flow regulation and the heterogeneity in blood vessel dilation patterns. We performed our experiments in awake mice, using a 3D+t two-photon imaging approach by which we could image regions at the branching point between PA and capillary bed at high speed. This led us to detect rapid, localized astrocytic Ca2+ signals in the end-feet surrounding the sphincter connecting the two vascular compartments. Mice often moved during experiments, and we noticed that in these cases, most of the natural vessel dilations in our imaged region were multicompartmental, extending from the PA to the 1storder capillary across the pre-capillary sphincter or vice versa. In contrast, when the mouse was at rest, dilations were more spatially restricted, with at least half of them remaining confined to one of the two compartments. The local Ca2+ rises in the end-feet encircling the pre-capillary sphincters preceded dilations spread and were notably correlated with multicompartment dilations. These Ca2+ signals were attenuated in IP3R2KO mice, lacking a major source of astrocyte Ca2+ rises, and the number of dilations crossing the sphincter was significantly reduced or slowed down compared to wild-type mice. When we induced dilations by auditory stimulation, we found that they had patterns and dependency on local astrocyte Ca2+ activity analogous to those of naturally occurring dilations. In conclusion, we discovered that pre-capillary sphincters play a pivotal role in the bidirectional dilation spread between vascular compartments and that local astrocyte Ca2+ signaling controls this function. This mechanism, described here for the first time, allows astrocytes to control the dilation transition across the sphincters and contribute to laminar blood flow regulation during neurovascular coupling responses.

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Section: Resultsmentioning

confidence: 99%

Fast 3D imaging in the auditory cortex of awake mice reveals that astrocytes control neurovascular coupling responses locally at arteriole-capillary junctions

Lind,

Volterra

2024

Preprint

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Tonic and burst-like locus coeruleus stimulation distinctly shift network activity across the cortical hierarchy

Grimm,

Duss,

Privitera

et al. 2024

Nat Neurosci

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Noradrenaline (NA) release from the locus coeruleus (LC) changes activity and connectivity in neuronal networks across the brain, modulating multiple behavioral states. NA release is mediated by both tonic and burst-like LC activity. However, it is unknown whether the functional changes in target areas depend on these firing patterns. Using optogenetics, photometry, electrophysiology and functional magnetic resonance imaging in mice, we show that tonic and burst-like LC firing patterns elicit brain responses that hinge on their distinct NA release dynamics. During moderate tonic LC activation, NA release engages regions associated with associative processing, while burst-like stimulation biases the brain toward sensory processing. These activation patterns locally couple with increased astrocytic and inhibitory activity and change the brain’s topological configuration in line with the hierarchical organization of the cerebral cortex. Together, these findings reveal how the LC–NA system achieves a nuanced regulation of global circuit operations.

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A spatial threshold for astrocyte calcium surge

Lines

Baraibar

Nanclares

et al. 2023

Preprint

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Astrocytes are active cells involved in brain function through the bidirectional communication with neurons, in which the astrocyte calcium signal plays a crucial role. Synaptically-evoked calcium increases can be localized to independent subcellular domains or expand to the entire cell, i.e., calcium surge. In turn, astrocytes may regulate individual synapses by calcium-dependent release of gliotransmitters. Because a single astrocyte may contact ~100,000 synapses, the control of the intracellular calcium signal propagation may have relevant consequences on brain function by regulating the spatial range of astrocyte neuromodulation of synapses. Yet, the properties governing the spatial dynamics of the astrocyte calcium signal remains poorly defined. Imaging subcellular responses of cortical astrocytes to sensory stimulation in mice, we show that sensory-evoked astrocyte calcium responses originated and remained localized in domains of the astrocytic arborization, but eventually propagated to the entire cell if a spatial threshold of >23% of the arborization being activated was surpassed. Using transgenic IP3R2-/- mice, we found that type-2 IP3 receptors were necessary for the generation of the astrocyte calcium surge. We finally show using in situ electrophysiological recordings that the spatial threshold of the astrocyte calcium signal consequently determined the gliotransmitter release. Present results reveal a fundamental property of astrocyte calcium physiology, i.e., a spatial threshold for the astrocyte intracellular calcium signal propagation, which depends on astrocyte intrinsic properties and governs the astrocyte integration of local synaptic activity and the subsequent neuromodulation.

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Centripetal integration of past events in hippocampal astrocytes regulated by locus coeruleus

Cited by 11 publications

References 78 publications

Fast 3D imaging in the auditory cortex of awake mice reveals that astrocytes control neurovascular coupling responses locally at arteriole-capillary junctions

Fast 3D imaging in the auditory cortex of awake mice reveals that astrocytes control neurovascular coupling responses locally at arteriole-capillary junctions

Tonic and burst-like locus coeruleus stimulation distinctly shift network activity across the cortical hierarchy

A spatial threshold for astrocyte calcium surge

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