The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index; none of the 25 sources its claims cite is checked for support yet.
Rapid Astrocyte Calcium Signals Correlate with Neuronal Activity and Onset of the Hemodynamic Response In Vivo
Open accessAbstract
Elevation of intracellular Ca2+ in astrocytes can influence cerebral microcirculation and modulate synaptic transmission. Recently, in vivo imaging studies identified delayed, sensory-driven Ca2+ oscillations in cortical astrocytes; however, the long latencies of these Ca2+ signals raises questions in regards to their suitability for a role in short-latency modulation of cerebral microcirculation or rapid astrocyte-to-neuron communication. Here, using in vivo two-photon Ca2+ imaging, we demonstrate that approximately 5% of sulforhodamine 101-labeled astrocytes in the hindlimb area of the mouse primary somatosensory cortex exhibit short-latency (peak amplitude approximately 0.5 s after stimulus onset), contralateral hindlimb-selective sensory-evoked Ca2+ signals that operate on a time scale similar to neuronal activity and correlate with the onset of the hemodynamic response as measured by intrinsic signal imaging. The kinetics of astrocyte Ca2+ transients were similar in rise and decay times to postsynaptic neuronal transients, but decayed more slowly than neuropil Ca2+ transients that presumably reflect presynaptic transients. These in vivo findings suggest that astrocytes can respond to sensory activity in a selective manner and process information on a subsecond time scale, enabling them to potentially form an active partnership with neurons for rapid regulation of microvascular tone and neuron-astrocyte network properties.
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TL;DR
In urethane-anesthetized mice, a small subset (~5%) of SR101-labeled astrocytes in hindlimb somatosensory cortex showed contralateral hindlimb-selective sensory-evoked Ca²⁺ signals peaking ~0.5 s after stimulus onset. These rapid astrocyte signals matched neuronal timescales and correlated with the onset of the hemodynamic response, suggesting astrocytes can respond on subsecond timescales relevant to neurovascular coupling.
Key findings
- Of 355 astrocytes (7 mice), 18 (5.07%; 5.08 ± 1.28% per mouse) showed above-threshold Ca²⁺ elevation after contralateral hindlimb stimulation; no other limbs induced significant responses. Astrocyte peak amplitude was 19.1 ± 1.7% ΔF/F₀.
- Time-to-peak did not differ significantly among astrocytes (0.41 ± 0.11 s), neurons (0.56 ± 0.09 s), and neuropil (0.43 ± 0.09 s; F(2,18) = 0.67; p = 0.52). Decay tau was shorter in neuropil (0.55 ± 0.04 s) than astrocytes (1.07 ± 0.17 s; p = 0.011) and neurons (1.21 ± 0.18 s; p = 0.005).
- The IOS hemodynamic response began ~600–800 ms after stimulus onset, while astrocyte Ca²⁺ peaked ~0.5 s after onset. Endfoot transients occurred in 12.7% of endfeet (n = 102; 4 mice), with peak 18.8 ± 5.4%, time-to-peak 0.73 ± 0.19 s, and decay tau 0.93 ± 0.10 s.
- Astrocyte responses were unlikely to be neuropil contamination: mean absolute OGB-1 fluorescence increase was 44.4 ± 5.1 gray levels in astrocytes vs 13.3 ± 1.4 in neuropil ROIs (t test, p << 0.001).
Methods
- Urethane-anesthetized C57B6 mice (male and female, 2–4 months). Intrinsic optical signal imaging mapped hindlimb/forelimb cortex during mechanical limb stimulation; two-photon Ca²⁺ imaging used OGB-1 and SR101 in layers I–III of hindlimb somatosensory cortex.
- 355 astrocytes across 7 mice; stimuli were 0.5–1.0 s at 3, 10, or 100 Hz. Responses were thresholded as ΔF/F₀ >1 SD over baseline for ≥0.5 s; ANOVA with post hoc t tests and Bonferroni correction was used, and G/R ratio controlled for movement artifact in high-resolution endfoot imaging.
Limitations
- The paper does not present a formal limitations section; it notes significant intertrial variability in endfoot Ca²⁺ responses.
- Evident from the text: only a small subset of astrocytes responded (~5%; 18 responsive astrocytes), imaging was limited to anesthetized mice and layers I–III of hindlimb cortex, and the study reports correlations with hemodynamic onset rather than causal manipulation of astrocyte Ca²⁺ or blood flow.
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12 Not checked yet · 7 Own interpretation · 7 Own result · 2 Own method
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Post hoc t tests using the Bonferroni correction revealed significantly shorter decay taus in neuropil ROIs (0.55 Ϯ 0.04 s) compared with astrocytes (1.07 Ϯ 0.17 s; p ϭ 0.011) and neurons (1.21 Ϯ 0.18 s; p ϭ 0.005).”
§ Rapid Astrocyte Calcium Signals Correlate with Neuronal Activity and Onset of the Hemodynamic Response In Vivo > Results
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“After the initial dip, increased blood flow (functional hyperemia) is associated with increased oxyhemoglobin concentration and blood volume, manifested in the IOS by increased light reflectance/decreased absorbance starting ϳ600 -800 ms after stimulus onset (Fig. 1 B) (Devor et al., 2003).”
§ Rapid Astrocyte Calcium Signals Correlate with Neuronal Activity and Onset of the Hemodynamic Response In Vivo > Results
What the sources say
- Not checked yetcites Devor et al., 2003
hedged- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“peak amplitude ϳ0.5 s after stimulus onset”
- Also stated in: § Results · plain
“Whereas time-to-peak (from stimulus onset) means did not differ significantly between astrocytes (0.41 Ϯ 0.11 s), neurons (0.56 Ϯ 0.09 s), and neuropil (0.43 Ϯ 0.09 s; F (2,18) ϭ 0.67; p ϭ 0.52)”
§ Rapid Astrocyte Calcium Signals Correlate with Neuronal Activity and Onset of the Hemodynamic Response In Vivo > Abstract
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Results · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Eighteen astrocytes (5.07% of total astrocytes; an average of 5.08 Ϯ 1.28% per mouse) showed an above-threshold stimulus-driven Ca 2ϩ elevation after cHL stimulation.”
§ Rapid Astrocyte Calcium Signals Correlate with Neuronal Activity and Onset of the Hemodynamic Response In Vivo > Results
plainn = 7- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The mean increases in absolute OGB-1 fluorescence (peak Ϫ F o ) in astrocytes (44.4 Ϯ 5.1 gray levels) during the 1.5 s after stimulation was significantly greater than the mean increase in fluorescence in neuropil ROIs (13.3 Ϯ 1.4 gray levels) in the same images (t test, p Ͻ Ͻ 0.001).”
§ Rapid Astrocyte Calcium Signals Correlate with Neuronal Activity and Onset of the Hemodynamic Response In Vivo > Results
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“No other limbs induced a significant Ca 2ϩ response.”
§ Rapid Astrocyte Calcium Signals Correlate with Neuronal Activity and Onset of the Hemodynamic Response In Vivo > Results
plainn = 7- Asserted: passes — The authors put it forward as true.
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Thresholds were set to identify cells where the change in Ca 2ϩ -induced fluorescence relative to baseline fluorescence was greater than one SD over baseline and remained above this criterion for at least 0.5 s (or three times the frame rate for frame rates Ͼ170 ms/frame).These criteria were found effective for separating responsive cells from noise.”
§ Rapid Astrocyte Calcium Signals Correlate with Neuronal Activity and Onset of the Hemodynamic Response In Vivo > Two-photon image processing.
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Furthermore, different subpopulations of protoplasmic astrocytes possess varying glutamate-receptor complements, and the shortand long-latency responses may reflect the activation of different glutamate receptors (Matthias et al., 2003;Wallraff et al., 2004;Jabs et al., 2005)”
§ Rapid Astrocyte Calcium Signals Correlate with Neuronal Activity and Onset of the Hemodynamic Response In Vivo > Discussion
What the sources say
- Not checked yetcites Matthias et al., 2003
- Not checked yetcites Wallraff et al., 2004
- Not checked yetcites Jabs et al., 2005
plaincorrelational- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Astrocytes also form a close physical and functional partnership with brain arterioles, because elevation of intracellular Ca 2ϩ in astrocyte endfeet is sufficient to trigger rapid changes in vascular tone (Zonta et al., 2003;Mulligan and MacVicar, 2004;Takano et al., 2006).”
§ Rapid Astrocyte Calcium Signals Correlate with Neuronal Activity and Onset of the Hemodynamic Response In Vivo > Introduction
What the sources say
- Not checked yetcites Zonta et al., 2003
- Not checked yetcites Mulligan and MacVicar, 2004
- Not checked yetcites Takano et al., 2006
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“G/R ratios confirm that this transient is selective to the Ca 2ϩ indicator and cannot be explained by movement artifact, which would affect both OGB-1 and SR101 channels.”
§ Rapid Astrocyte Calcium Signals Correlate with Neuronal Activity and Onset of the Hemodynamic Response In Vivo > Results
plainSingle case- Asserted: passes — The authors put it forward as true.
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- The quote only partly states this claim. 1
- It may state two separate claims as one. 4
- Probably not a substantial claim. 4
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The mean decay taus of astrocytes and neurons were not significantly different ( p ϭ 0.59).”
§ Rapid Astrocyte Calcium Signals Correlate with Neuronal Activity and Onset of the Hemodynamic Response In Vivo > Results
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The quote only partly states this claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Approximately 20 -30% of neurons and most neuropil ROIs in the same image planes showed Ca 2ϩ responses above threshold criteria.”
§ Rapid Astrocyte Calcium Signals Correlate with Neuronal Activity and Onset of the Hemodynamic Response In Vivo > Results
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“and metabotropic glutamate receptors and glutamate uptake transporters on astrocytes have been implicated in the hemodynamic response to neuronal activity (Gurden et al., 2006;Takano et al., 2006).”
§ Rapid Astrocyte Calcium Signals Correlate with Neuronal Activity and Onset of the Hemodynamic Response In Vivo > Introduction
What the sources say
- Not checked yetcites Gurden et al., 2006
- Not checked yetcites Takano et al., 2006
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These in vivo findings suggest that astrocytes can respond to sensory activity in a selective manner and process information on a subsecond time scale”
§ Rapid Astrocyte Calcium Signals Correlate with Neuronal Activity and Onset of the Hemodynamic Response In Vivo > Abstract
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“It has been suggested that neuron-to-astrocyte communication may be a key mediator of this functional hyperemia (Zonta et al., 2003;Takano et al., 2006)”
§ Rapid Astrocyte Calcium Signals Correlate with Neuronal Activity and Onset of the Hemodynamic Response In Vivo > Introduction
What the sources say
- Not checked yetcites Zonta et al., 2003
- Not checked yetcites Takano et al., 2006
hedgedconditional- Asserted: fails — The authors may not put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The authors may not put it forward as true.
None of the sources cited for this claim have been checked yet.
In the paper
“Previous evidence indicates that hyperemia begins ϳ600 ms after sensory stimulus onset and, thus, would require a rapid response from astrocytes (Kleinfeld et al., 1998;Devor et al., 2003).”
§ Rapid Astrocyte Calcium Signals Correlate with Neuronal Activity and Onset of the Hemodynamic Response In Vivo > Discussion
What the sources say
- Not checked yetcites Kleinfeld et al., 1998
- Not checked yetcites Devor et al., 2003
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The presence of ionotropic glutamate receptors and rapid transporter-mediated currents suggest that astrocytes can communicate with neurons on a rapid subsecond time scale, and in vitro and in situ studies have shown that astrocyte Ca 2ϩ transients and synaptic-like currents can be triggered by neuronal activity (Dani et al., 1992;Murphy et al., 1993;Porter andMcCarthy, 1995a,b, 1996;Bergles and”
§ Rapid Astrocyte Calcium Signals Correlate with Neuronal Activity and Onset of the Hemodynamic Response In Vivo > Introduction
What the sources say
- Not checked yetcites Dani et al., 1992
- Not checked yetcites Murphy et al., 1993
- Not checked yetcites Porter andMcCarthy, 1995a,b
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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Probably not a substantial claim. It may state two separate claims as one.
In the paper
“although the authors note the large amplitude, long-lasting Ca 2ϩ oscillations that propagate throughout the glial network, careful examination of the data presented suggests that smaller, short-latency Ca 2ϩ transients were also triggered by electrical stimulation in some astrocytes.”
§ Rapid Astrocyte Calcium Signals Correlate with Neuronal Activity and Onset of the Hemodynamic Response In Vivo > Discussion
What the sources say
- Not checked yetcites Gobel et al., 2007
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“In vivo imaging studies of astrocytes have shown that astrocytes are sensitive to changes in neural activity and respond with increases in intracellular calcium levels (Wang et al., 2006; Winship et al., 2007).”
From Adult neurogenesis, glia, and the extracellular matrix (2019) · cites this paper as Winship et al., 2007
Citations
Cites
Protoplasmic Astrocytes in CA1 Stratum Radiatum Occupy Separate Anatomical Domains
Bushong, E. A., Martone, M. E., Jones, Y. Z., & Ellisman, M. H. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-01-00183.2002 · Cited by 1,578
Neuron-to-astrocyte signaling is central to the dynamic control of brain microcirculation
Zonta, M., Angulo, M. C., Gobbo, S., Rosengarten, B., Hossmann, K.-A., Pozzan, T., & Carmignoto, G. (2002) · Nature Neuroscience · doi:10.1038/nn980 · Cited by 1,446
Astrocyte Control of Synaptic Transmission and Neurovascular Coupling
Haydon, P. G., & Carmignoto, G. (2006) · Physiological Reviews · doi:10.1152/physrev.00049.2005 · Cited by 1,371
In vivo two-photon calcium imaging of neuronal networks
Stosiek, C., Garaschuk, O., Holthoff, K., & Konnerth, A. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1232232100 · Cited by 1,341
Astrocyte-mediated control of cerebral blood flow
Takano, T., Tian, G.-F., Peng, W., Lou, N., Libionka, W., Han, X., & Nedergaard, M. (2005) · Nature Neuroscience · doi:10.1038/nn1623 · Cited by 1,137
Fellin, T., Pascual, O., Gobbo, S., Pozzan, T., Haydon, P. G., & Carmignoto, G. (2004) · Neuron · doi:10.1016/j.neuron.2004.08.011 · Cited by 1,005
Frostig, R. D., Lieke, E. E., Ts’o, D. Y., & Grinvald, A. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.16.6082 · Cited by 959
Calcium transients in astrocyte endfeet cause cerebrovascular constrictions
Mulligan, S. J., & MacVicar, B. A. (2004) · Nature · doi:10.1038/nature02827 · Cited by 872
Kleinfeld, D., Mitra, P. P., Helmchen, F., & Denk, W. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.26.15741 · Cited by 832
Neuronal activity triggers calcium waves in hippocampal astrocyte networks
Dani, J. W., Chernjavsky, A., & Smith, S. J. (1992) · Neuron · doi:10.1016/0896-6273(92)90271-e · Cited by 823
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Gliotransmitters Travel in Time and Space
Araque, A., Carmignoto, G., Haydon, P. G., Oliet, S. H. R., Robitaille, R., & Volterra, A. (2014) · Neuron · doi:10.1016/j.neuron.2014.02.007 · Cited by 1,308
Glial regulation of the cerebral microvasculature
Iadecola, C., & Nedergaard, M. (2007) · Nature Neuroscience · doi:10.1038/nn2003 · Cited by 1,153
Astrocyte calcium signaling: the third wave
Bazargani, N., & Attwell, D. (2016) · Nature Neuroscience · doi:10.1038/nn.4201 · Cited by 998
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Metadata
- Authors
- Winship, I. R., Plaa, N., & Murphy, T. H.
- Affiliations
- University of British Columbia (CA)
- Venue
- Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2007-06-06
- Volume
- 27
- Issue
- 23
- Pages
- 6268-6272
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6672142
- OpenAlex
- W2054459050
- Semantic Scholar
- 9c442e4e61461e8b7b1b77e7f83d93c39f83a302
- Cited by
- 221
- References
- 32
- Citations by year
- 2025: 7 · 2024: 4 · 2023: 12 · 2022: 9 · 2021: 11 · 2020: 9 · 2019: 5 · 2018: 8 · 2017: 9 · 2016: 16 · 2015: 17 · 2014: 14 · 2013: 21 · 2012: 19
- FWCI
- 6.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Heart and Stroke Foundation of Canada
- Canadian Stroke Network
- Michael Smith Health Research BC
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- calcium oscillations, sensory evoked potentials, primary somatosensory cortex, hemodynamic response, astrocyte-neuron communication, cerebral microcirculation, sulforhodamine 101, intrinsic signal imaging, microvascular tone, neuronal activity
- MeSH terms
- Action Potentials, Animals, Astrocytes, Female, Hindlimb, Male, Mice, Inbred C57BL, Microcirculation, Neurons, Somatosensory Cortex, Time Factors, Calcium Signaling, Mice
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