Neuronal networks and mediators of cortical neurovascular coupling responses in normal and altered brain states

Lecrux, Clotilde; Hamel, Edith

doi:10.1098/rstb.2015.0350

Cited by 104 publications

(107 citation statements)

References 174 publications

(276 reference statements)

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“…Typically, fMRI measures the blood oxygenation-level dependent (BOLD) signal, which is generally believed to be spatiotemporally linked to neural activity through the mechanism of neurovascular coupling (Hillman, 2014; Kim and Ogawa, 2012; Lecrux and Hamel, 2016). Neurovascular coupling is a highly complex physiological process that involves many types of brain cells, including excitatory pyramidal neurons, interneurons, astrocytes, pericytes, endothelia cells and smooth muscles.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous GCaMP6-based fiber photometry and fMRI in rats

Liang

Watson

et al. 2017

Journal of Neuroscience Methods

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Background Understanding the relationship between neural and vascular signals is essential for interpretation of functional MRI (fMRI) results with respect to underlying neuronal activity. Simultaneously measuring neural activity using electrophysiology with fMRI has been highly valuable in elucidating the neural basis of the blood oxygenation-level dependent (BOLD) signal. However, this approach is also technically challenging due to the electromagnetic interference that is observed in electrophysiological recordings during MRI scanning. New Method Recording optical correlates of neural activity, such as calcium signals, avoids this issue, and has opened a new avenue to simultaneously acquire neural and BOLD signals. Results The present study is the first to demonstrate the feasibility of simultaneously and repeatedly acquiring calcium and BOLD signals in animals using a genetically encoded calcium indicator, GCaMP6. This approach was validated with a visual stimulation experiment, during which robust increases of both calcium and BOLD signals in the superior colliculus were observed. In addition, repeated measurement in the same animal demonstrated reproducible calcium and BOLD responses to the same stimuli. Comparison with Existing Method(s) Taken together, simultaneous GCaMP6-based fiber photometry and fMRI recording presents a novel, artifact-free approach to simultaneously measuring neural and fMRI signals. Furthermore, given the cell-type specificity of GCaMP6, this approach has the potential to mechanistically dissect the contributions of individual neuron populations with respect to BOLD signal, and ultimately reveal its underlying neural mechanisms. Conclusions The current study established the method for simultaneous GCaMP6-based fiber photometry and fMRI in rats.

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Section: Introductionmentioning

confidence: 99%

Simultaneous GCaMP6-based fiber photometry and fMRI in rats

Liang

Watson

et al. 2017

Journal of Neuroscience Methods

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“…This relationship between the BOLD signal and neuronal activity is extensively discussed in previous reviews [1][2] and other papers in this issue [3][4][5]. Box 1 provides an introduction to the origin of the BOLD signal.…”

Section: What Do We Know About Bold? (A) An Increase In the Positivementioning

confidence: 95%

“…Release of neurotransmitters such as glutamate induces dilation of cerebral blood vessels by triggering the release of vasoactive signalling molecules from both neurons and glia (LeCrux and Hamel, and Uhlirova et al in this issue; [3,4,7]). Much is now known about these signalling pathways, but their variability across brain areas and circuits is likely to lead to differences in neurovascular coupling properties and therefore also to variations in the relationship between BOLD and neuronal activity across different brain regions and experimental conditions (discussed below).…”

Section: What Do We Know About Bold? (A) An Increase In the Positivementioning

confidence: 99%

“…This is achieved through neurovascular coupling. Work over the past two decades has attempted to define the signalling mechanisms that give rise to neurovascular coupling (see the main text, Lecrux and Hamel [3] in this issue and [7]), which is exploited by the BOLD fMRI technique to visualize neuronal activation. BOLD contrast is dependent on the level of deoxyhaemoglobin in the blood [8].…”

Section: Cellular Mechanisms Underlying Bold: How Our Incomplete Undementioning

confidence: 99%

“…The mechanisms underlying neurovascular coupling in a given situation will vary depending on expression patterns of key enzymes and receptors across different brain areas, as well as the local and global circuit dynamics engaged by a given task. For example, different subtypes of inhibitory interneurons presumably alter neurovascular coupling not only by the release of different vasoactive molecules, but also by regulating the activity of the local network (Lecrux and Hamel [3] in this issue; [74]), affecting glutamate release and second messenger production in excitatory neurons and astrocytes. As discussed above, the activity of these circuits and the reactivity of blood vessels may also be affected by global brain state as expressed in different levels of monoaminergic and cholinergic tone.…”

Section: (D) Central Neuromodulatory Pathwaysmentioning

confidence: 99%

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Interpreting BOLD: towards a dialogue between cognitive and cellular neuroscience

Hall

Howarth

Kurth-Nelson

et al. 2016

Phil. Trans. R. Soc. B

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Cognitive neuroscience depends on the use of blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to probe brain function. Although commonly used as a surrogate measure of neuronal activity, BOLD signals actually reflect changes in brain blood oxygenation. Understanding the mechanisms linking neuronal activity to vascular perfusion is, therefore, critical in interpreting BOLD. Advances in cellular neuroscience demonstrating differences in this neurovascular relationship in different brain regions, conditions or pathologies are often not accounted for when interpreting BOLD. Meanwhile, within cognitive neuroscience, the increasing use of high magnetic field strengths and the development of model-based tasks and analyses have broadened the capability of BOLD signals to inform us about the underlying neuronal activity, but these methods are less well understood by cellular neuroscientists. In 2016, a Royal Society Theo Murphy Meeting brought scientists from the two communities together to discuss these issues. Here, we consolidate the main conclusions arising from that meeting. We discuss areas of consensus about what BOLD fMRI can tell us about underlying neuronal activity, and how advanced modelling techniques have improved our ability to use and interpret BOLD. We also highlight areas of controversy in understanding BOLD and suggest research directions required to resolve these issues. This article is part of the themed issue ‘Interpreting BOLD: a dialogue between cognitive and cellular neuroscience’.

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Glutamate triggers intracellular Ca²⁺ oscillations and nitric oxide release by inducing NAADP‐ and InsP₃‐dependent Ca²⁺ release in mouse brain endothelial cells

Zuccolo

Kheder

Lim

et al. 2018

Journal Cellular Physiology

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The neurotransmitter glutamate increases cerebral blood flow by activating postsynaptic neurons and presynaptic glial cells within the neurovascular unit. Glutamate does so by causing an increase in intracellular Ca 2+ concentration ([Ca 2+ ] i ) in the target cells, which activates the Ca 2+ /Calmodulin-dependent nitric oxide (NO) synthase to release NO. It is unclear whether brain endothelial cells also sense glutamate through an elevation in [Ca 2+ ] i and NO production. The current study assessed whether and how glutamate drives Ca 2+dependent NO release in bEND5 cells, an established model of brain endothelial cells. We found that glutamate induced a dose-dependent oscillatory increase in [Ca 2+ ] i , which was maximally activated at 200 μM and inhibited by α-methyl-4-carboxyphenylglycine, a selective blocker of Group 1 metabotropic glutamate receptors. Glutamate-induced intracellular Ca 2+ oscillations were triggered by rhythmic endogenous Ca 2+ mobilization and maintained over time by extracellular Ca 2+ entry. Pharmacological manipulation revealed that glutamate-induced endogenous Ca 2+ release was mediated by InsP 3 -sensitive receptors and nicotinic acid adenine dinucleotide phosphate (NAADP) J Cell Physiol. 2019;234:3538-3554. wileyonlinelibrary.com/journal/jcp 3538 | gated two-pore channel 1. Constitutive store-operated Ca 2+ entry mediated Ca 2+ entry during ongoing Ca 2+ oscillations. Finally, glutamate evoked a robust, although delayed increase in NO levels, which was blocked by pharmacologically inhibition of the accompanying intracellular Ca 2+ signals. Of note, glutamate induced Ca 2+ -dependent NO release also in hCMEC/D3 cells, an established model of human brain microvascular endothelial cells. This investigation demonstrates for the first time that metabotropic glutamate-induced intracellular Ca 2+ oscillations and NO release have the potential to impact on neurovascular coupling in the brain. K E Y W O R D S Ca 2+ oscillations, endothelial cells, glutamate, neurovascular coupling (NVC), nitric oxide

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Neuronal networks and mediators of cortical neurovascular coupling responses in normal and altered brain states

Cited by 104 publications

References 174 publications

Simultaneous GCaMP6-based fiber photometry and fMRI in rats

Simultaneous GCaMP6-based fiber photometry and fMRI in rats

Interpreting BOLD: towards a dialogue between cognitive and cellular neuroscience

Glutamate triggers intracellular Ca²⁺ oscillations and nitric oxide release by inducing NAADP‐ and InsP₃‐dependent Ca²⁺ release in mouse brain endothelial cells

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Neuronal networks and mediators of cortical neurovascular coupling responses in normal and altered brain states

Cited by 104 publications

References 174 publications

Simultaneous GCaMP6-based fiber photometry and fMRI in rats

Simultaneous GCaMP6-based fiber photometry and fMRI in rats

Interpreting BOLD: towards a dialogue between cognitive and cellular neuroscience

Glutamate triggers intracellular Ca2+ oscillations and nitric oxide release by inducing NAADP‐ and InsP3‐dependent Ca2+ release in mouse brain endothelial cells

Contact Info

Product

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Glutamate triggers intracellular Ca²⁺ oscillations and nitric oxide release by inducing NAADP‐ and InsP₃‐dependent Ca²⁺ release in mouse brain endothelial cells