In Vivo Stimulus-induced Vasodilation Occurs Without IP3 Receptor Activation and May Precede Astrocytic Calcium Increase

Overview

Journal J Neurosci

Specialty Neurology

Date 2013 May 10

PMID 23658179

Citations 123

Authors

Krystal Nizar

Hana Uhlirova

Peifang Tian

Payam A Saisan

Qun Cheng

Lidia Reznichenko

Kimberly L Weldy

Tyler C Steed

Vishnu B Sridhar

Christopher L Macdonald

Jianxia Cui

Sergey L Gratiy

Sava Sakadzic

David A Boas

Thomas I Beka

Gaute T Einevoll

Ju Chen

Eliezer Masliah

Anders M Dale

Gabriel A Silva

Anna Devor

Affiliations

Soon will be listed here.

Abstract

Calcium-dependent release of vasoactive gliotransmitters is widely assumed to trigger vasodilation associated with rapid increases in neuronal activity. Inconsistent with this hypothesis, intact stimulus-induced vasodilation was observed in inositol 1,4,5-triphosphate (IP3) type-2 receptor (R2) knock-out (KO) mice, in which the primary mechanism of astrocytic calcium increase-the release of calcium from intracellular stores following activation of an IP3-dependent pathway-is lacking. Further, our results in wild-type (WT) mice indicate that in vivo onset of astrocytic calcium increase in response to sensory stimulus could be considerably delayed relative to the simultaneously measured onset of arteriolar dilation. Delayed calcium increases in WT mice were observed in both astrocytic cell bodies and perivascular endfeet. Thus, astrocytes may not play a role in the initiation of blood flow response, at least not via calcium-dependent mechanisms. Moreover, an increase in astrocytic intracellular calcium was not required for normal vasodilation in the IP3R2-KO animals.

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.

Revisiting astrocytic calcium signaling in the brain.

Bai Y, Zhou Z, Han B, Xiang X, Huang W, Yao H Fundam Res. 2024; 4(6):1365-1374.

PMID: 39734522 PMC: 11670731. DOI: 10.1016/j.fmre.2023.11.021.

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

Grimm C, Duss S, Privitera M, Munn B, Karalis N, Frassle S Nat Neurosci. 2024; 27(11):2167-2177.

PMID: 39284964 PMC: 11537968. DOI: 10.1038/s41593-024-01755-8.

Multiphoton fluorescence microscopy for in vivo imaging.

Xu C, Nedergaard M, Fowell D, Friedl P, Ji N Cell. 2024; 187(17):4458-4487.

PMID: 39178829 PMC: 11373887. DOI: 10.1016/j.cell.2024.07.036.

The role of neurovascular coupling dysfunction in cognitive decline of diabetes patients.

Feng L, Gao L Front Neurosci. 2024; 18:1375908.

PMID: 38576869 PMC: 10991808. DOI: 10.3389/fnins.2024.1375908.

References

Shigetomi E, Kracun S, Khakh B . Monitoring astrocyte calcium microdomains with improved membrane targeted GCaMP reporters. Neuron Glia Biol. 2011; 6(3):183-91. PMC: 3136572. DOI: 10.1017/S1740925X10000219. View

Agulhon C, Petravicz J, McMullen A, Sweger E, Minton S, Taves S . What is the role of astrocyte calcium in neurophysiology?. Neuron. 2008; 59(6):932-46. PMC: 3623689. DOI: 10.1016/j.neuron.2008.09.004. View

Takano T, Tian G, Peng W, Lou N, Libionka W, Han X . Astrocyte-mediated control of cerebral blood flow. Nat Neurosci. 2006; 9(2):260-7. DOI: 10.1038/nn1623. View

Fiacco T, McCarthy K . Astrocyte calcium elevations: properties, propagation, and effects on brain signaling. Glia. 2006; 54(7):676-690. DOI: 10.1002/glia.20396. View

Reeves A, Shigetomi E, Khakh B . Bulk loading of calcium indicator dyes to study astrocyte physiology: key limitations and improvements using morphological maps. J Neurosci. 2011; 31(25):9353-8. PMC: 3142876. DOI: 10.1523/JNEUROSCI.0127-11.2011. View

Takata N, Mishima T, Hisatsune C, Nagai T, Ebisui E, Mikoshiba K . Astrocyte calcium signaling transforms cholinergic modulation to cortical plasticity in vivo. J Neurosci. 2011; 31(49):18155-65. PMC: 6634158. DOI: 10.1523/JNEUROSCI.5289-11.2011. View

Anderson L, Christianson G, Linden J . Mouse auditory cortex differs from visual and somatosensory cortices in the laminar distribution of cytochrome oxidase and acetylcholinesterase. Brain Res. 2008; 1252:130-42. DOI: 10.1016/j.brainres.2008.11.037. View

Lecrux C, Toussay X, Kocharyan A, Fernandes P, Neupane S, Levesque M . Pyramidal neurons are "neurogenic hubs" in the neurovascular coupling response to whisker stimulation. J Neurosci. 2011; 31(27):9836-47. PMC: 6703330. DOI: 10.1523/JNEUROSCI.4943-10.2011. View

Devor A, Ulbert I, Dunn A, Narayanan S, Jones S, Andermann M . Coupling of the cortical hemodynamic response to cortical and thalamic neuronal activity. Proc Natl Acad Sci U S A. 2005; 102(10):3822-7. PMC: 550644. DOI: 10.1073/pnas.0407789102. View

10.

Dombeck D, Khabbaz A, Collman F, Adelman T, Tank D . Imaging large-scale neural activity with cellular resolution in awake, mobile mice. Neuron. 2007; 56(1):43-57. PMC: 2268027. DOI: 10.1016/j.neuron.2007.08.003. View

11.

Buzsaki G . Large-scale recording of neuronal ensembles. Nat Neurosci. 2004; 7(5):446-51. DOI: 10.1038/nn1233. View

12.

Nimmerjahn A, Kirchhoff F, Kerr J, Helmchen F . Sulforhodamine 101 as a specific marker of astroglia in the neocortex in vivo. Nat Methods. 2005; 1(1):31-7. DOI: 10.1038/nmeth706. View

13.

Petravicz J, Fiacco T, McCarthy K . Loss of IP3 receptor-dependent Ca2+ increases in hippocampal astrocytes does not affect baseline CA1 pyramidal neuron synaptic activity. J Neurosci. 2008; 28(19):4967-73. PMC: 2709811. DOI: 10.1523/JNEUROSCI.5572-07.2008. View

14.

Steriade M . Grouping of brain rhythms in corticothalamic systems. Neuroscience. 2005; 137(4):1087-106. DOI: 10.1016/j.neuroscience.2005.10.029. View

15.

Wang X, Takano T, Nedergaard M . Astrocytic calcium signaling: mechanism and implications for functional brain imaging. Methods Mol Biol. 2008; 489:93-109. PMC: 3638986. DOI: 10.1007/978-1-59745-543-5_5. View

16.

Simard M, Arcuino G, Takano T, Liu Q, Nedergaard M . Signaling at the gliovascular interface. J Neurosci. 2003; 23(27):9254-62. PMC: 6740832. View

17.

Winship I, Plaa N, Murphy T . Rapid astrocyte calcium signals correlate with neuronal activity and onset of the hemodynamic response in vivo. J Neurosci. 2007; 27(23):6268-72. PMC: 6672142. DOI: 10.1523/JNEUROSCI.4801-06.2007. View

18.

Bergles D, Jahr C . Synaptic activation of glutamate transporters in hippocampal astrocytes. Neuron. 1998; 19(6):1297-308. DOI: 10.1016/s0896-6273(00)80420-1. View

19.

Poskanzer K, Yuste R . Astrocytic regulation of cortical UP states. Proc Natl Acad Sci U S A. 2011; 108(45):18453-8. PMC: 3215035. DOI: 10.1073/pnas.1112378108. View

20.

Calcinaghi N, Jolivet R, Wyss M, Ametamey S, Gasparini F, Buck A . Metabotropic glutamate receptor mGluR5 is not involved in the early hemodynamic response. J Cereb Blood Flow Metab. 2011; 31(9):e1-10. PMC: 3185891. DOI: 10.1038/jcbfm.2011.96. View