Calcium Dynamics in Astrocyte Processes During Neurovascular Coupling

Overview

Journal Nat Neurosci

Date 2014 Dec 23

PMID 25531572

Citations 148

Authors

Yo Otsu

Kiri Couchman

Declan G Lyons

Mayeul Collot

Amit Agarwal

Jean-Maurice Mallet

Frank W Pfrieger

Dwight E Bergles

Serge Charpak

Affiliations

Soon will be listed here.

Abstract

Enhanced neuronal activity in the brain triggers a local increase in blood flow, termed functional hyperemia, via several mechanisms, including calcium (Ca(2+)) signaling in astrocytes. However, recent in vivo studies have questioned the role of astrocytes in functional hyperemia because of the slow and sparse dynamics of their somatic Ca(2+) signals and the absence of glutamate metabotropic receptor 5 in adults. Here, we reexamined their role in neurovascular coupling by selectively expressing a genetically encoded Ca(2+) sensor in astrocytes of the olfactory bulb. We show that in anesthetized mice, the physiological activation of olfactory sensory neuron (OSN) terminals reliably triggers Ca(2+) increases in astrocyte processes but not in somata. These Ca(2+) increases systematically precede the onset of functional hyperemia by 1-2 s, reestablishing astrocytes as potential regulators of neurovascular coupling.

Citing Articles

From Mechanisms to Medicine: Neurovascular Coupling in the Diagnosis and Treatment of Cerebrovascular Disorders: A Narrative Review.

Yang L, Zhao W, Kan Y, Ren C, Ji X Cells. 2025; 14(1.

PMID: 39791717 PMC: 11719775. DOI: 10.3390/cells14010016.

In Vivo Neurodynamics Mapping via High-Speed Two-Photon Fluorescence Lifetime Volumetric Projection Microscopy.

Li Y, Xu X, Zhang C, Sun X, Zhou S, Li X Adv Sci (Weinh). 2024; 12(7):e2410605.

PMID: 39716869 PMC: 11831470. DOI: 10.1002/advs.202410605.

A spatial threshold for astrocyte calcium surge.

Lines J, Baraibar A, Nanclares C, Martin E, Aguilar J, Kofuji P Elife. 2024; 12.

PMID: 39680037 PMC: 11649242. DOI: 10.7554/eLife.90046.

Astrocyte-mediated neuronal irregularities and dynamics: the complexity of the tripartite synapse.

Garcia D, Jacquir S Biol Cybern. 2024; 118(5-6):249-266.

PMID: 39276225 DOI: 10.1007/s00422-024-00994-z.

Astrocytic activation increases blood flow in the adult olfactory bulb.

Ogino T, Agetsuma M, Sawada M, Inada H, Nabekura J, Sawamoto K Mol Brain. 2024; 17(1):52.

PMID: 39107815 PMC: 11301997. DOI: 10.1186/s13041-024-01126-1.

References

Di Castro M, Chuquet J, Liaudet N, Bhaukaurally K, Santello M, Bouvier D . Local Ca2+ detection and modulation of synaptic release by astrocytes. Nat Neurosci. 2011; 14(10):1276-84. DOI: 10.1038/nn.2929. View

Roux L, Benchenane K, Rothstein J, Bonvento G, Giaume C . Plasticity of astroglial networks in olfactory glomeruli. Proc Natl Acad Sci U S A. 2011; 108(45):18442-6. PMC: 3214998. DOI: 10.1073/pnas.1107386108. View

Masamoto K, Kanno I . Anesthesia and the quantitative evaluation of neurovascular coupling. J Cereb Blood Flow Metab. 2012; 32(7):1233-47. PMC: 3390804. DOI: 10.1038/jcbfm.2012.50. View

Schulz K, Sydekum E, Krueppel R, Engelbrecht C, Schlegel F, Schroter A . Simultaneous BOLD fMRI and fiber-optic calcium recording in rat neocortex. Nat Methods. 2012; 9(6):597-602. DOI: 10.1038/nmeth.2013. View

Sun W, McConnell E, Pare J, Xu Q, Chen M, Peng W . Glutamate-dependent neuroglial calcium signaling differs between young and adult brain. Science. 2013; 339(6116):197-200. PMC: 3569008. DOI: 10.1126/science.1226740. View

Shigetomi E, Bushong E, Haustein M, Tong X, Jackson-Weaver O, Kracun S . Imaging calcium microdomains within entire astrocyte territories and endfeet with GCaMPs expressed using adeno-associated viruses. J Gen Physiol. 2013; 141(5):633-47. PMC: 3639581. DOI: 10.1085/jgp.201210949. View

Nizar K, Uhlirova H, Tian P, Saisan P, Cheng Q, Reznichenko L . In vivo stimulus-induced vasodilation occurs without IP3 receptor activation and may precede astrocytic calcium increase. J Neurosci. 2013; 33(19):8411-22. PMC: 3712855. DOI: 10.1523/JNEUROSCI.3285-12.2013. View

Takata N, Nagai T, Ozawa K, Oe Y, Mikoshiba K, Hirase H . Cerebral blood flow modulation by Basal forebrain or whisker stimulation can occur independently of large cytosolic Ca2+ signaling in astrocytes. PLoS One. 2013; 8(6):e66525. PMC: 3681769. DOI: 10.1371/journal.pone.0066525. View

Lind B, Brazhe A, Jessen S, Tan F, Lauritzen M . Rapid stimulus-evoked astrocyte Ca2+ elevations and hemodynamic responses in mouse somatosensory cortex in vivo. Proc Natl Acad Sci U S A. 2013; 110(48):E4678-87. PMC: 3845114. DOI: 10.1073/pnas.1310065110. View

10.

Dunn K, Nelson M . Neurovascular signaling in the brain and the pathological consequences of hypertension. Am J Physiol Heart Circ Physiol. 2013; 306(1):H1-14. PMC: 3920149. DOI: 10.1152/ajpheart.00364.2013. View

11.

Hall C, Reynell C, Gesslein B, Hamilton N, Mishra A, Sutherland B . Capillary pericytes regulate cerebral blood flow in health and disease. Nature. 2014; 508(7494):55-60. PMC: 3976267. DOI: 10.1038/nature13165. View

12.

Rusakov D, Bard L, Stewart M, Henneberger C . Diversity of astroglial functions alludes to subcellular specialisation. Trends Neurosci. 2014; 37(4):228-42. DOI: 10.1016/j.tins.2014.02.008. View

13.

Volterra A, Liaudet N, Savtchouk I . Astrocyte Ca²⁺ signalling: an unexpected complexity. Nat Rev Neurosci. 2014; 15(5):327-35. DOI: 10.1038/nrn3725. View

14.

Haustein M, Kracun S, Lu X, Shih T, Jackson-Weaver O, Tong X . Conditions and constraints for astrocyte calcium signaling in the hippocampal mossy fiber pathway. Neuron. 2014; 82(2):413-29. PMC: 4086217. DOI: 10.1016/j.neuron.2014.02.041. View

15.

Paukert M, Agarwal A, Cha J, Doze V, Kang J, Bergles D . Norepinephrine controls astroglial responsiveness to local circuit activity. Neuron. 2014; 82(6):1263-70. PMC: 4080721. DOI: 10.1016/j.neuron.2014.04.038. View

16.

Oheim M, van t Hoff M, Feltz A, Zamaleeva A, Mallet J, Collot M . New red-fluorescent calcium indicators for optogenetics, photoactivation and multi-color imaging. Biochim Biophys Acta. 2014; 1843(10):2284-306. DOI: 10.1016/j.bbamcr.2014.03.010. View

17.

Bonder D, McCarthy K . Astrocytic Gq-GPCR-linked IP3R-dependent Ca2+ signaling does not mediate neurovascular coupling in mouse visual cortex in vivo. J Neurosci. 2014; 34(39):13139-50. PMC: 4172806. DOI: 10.1523/JNEUROSCI.2591-14.2014. View

18.

Jego P, Pacheco-Torres J, Araque A, Canals S . Functional MRI in mice lacking IP3-dependent calcium signaling in astrocytes. J Cereb Blood Flow Metab. 2014; 34(10):1599-603. PMC: 4269735. DOI: 10.1038/jcbfm.2014.144. View

19.

Lecoq J, Tiret P, Charpak S . Peripheral adaptation codes for high odor concentration in glomeruli. J Neurosci. 2009; 29(10):3067-72. PMC: 6666444. DOI: 10.1523/JNEUROSCI.6187-08.2009. View

20.

Shigetomi E, Kracun S, Sofroniew M, Khakh B . A genetically targeted optical sensor to monitor calcium signals in astrocyte processes. Nat Neurosci. 2010; 13(6):759-66. PMC: 2920135. DOI: 10.1038/nn.2557. View