Astrocytic and neuronal oxidative metabolism are coupled to the rate of glutamate–glutamine cycle in the tree shrew visual cortex

Sonnay, Sarah; Poirot, Jordan; Just, Nathalie; Clerc, Anne Catherine; Gruetter, Rolf; Rainer, Gregor; Duarte, João M. N.

doi:10.1002/glia.23259

Cited by 49 publications

(69 citation statements)

References 68 publications

(102 reference statements)

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“…Previous 1 H‐fMRS in the rat cortex were conducted in larger VOIs (16 µL (Just et al ) and 31.5 µL (Xu et al )) under α‐chloralose anesthesia. These previous sensory stimulations were performed using prolonged stimulation paradigms lasting 10–30 min in the rodent cortex (Just et al ; ; Just and Sonnay, ; Sonnay et al ). In the present work, we chose to use a repeated block paradigm of stimulation in line with previous 1 H‐fMRS in humans (Mangia et al a,b; Schaller et al ,; Lin et al ) allowing the assessment of repeated dynamics of metabolites.…”

Section: Discussionmentioning

confidence: 99%

“…In rodents, positive changes in lactate (Lac) and glutamate (Glu) and negative changes in Glucose (Glc) and aspartate (Asp), supportive of increased oxidative metabolism were obtained (Just et al ). The quality of results strongly depended on experimental conditions, in particular the anesthesia, the number of animals, the size of the voxel of interest (VOI), and the quality of shimming (Just and Sonnay, ; Sonnay et al ; Sonnay et al ). In the human brain, large VOIs imply averaging over different cell types that cannot be easily resolved (Bednařík et al ).…”

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confidence: 99%

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Probing activation‐induced neurochemical changes using optogenetics combined with functional magnetic resonance spectroscopy: a feasibility study in the rat primary somatosensory cortex

Just

Faber

2019

Journal of Neurochemistry

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Knowledge about biochemical processes is a prerequisite for a better understanding of mechanisms underlying brain activity. 1H functional magnetic resonance spectroscopy (1H‐fMRS) at high magnetic fields allows for the non‐invasive measurement of metabolic changes during brain activation. Optogenetics, on the other hand, has revolutionized the field of neuroscience. It was previously coupled with functional magnetic resonance imaging (fMRI) techniques in rodents enabling population‐specific targeting of cells, investigating brain networks with unprecedented in vivo precision. The coupling of optogenetics and 1H‐fMRS is expected to enhance the specificity of metabolic readouts to validate neuro‐energetic theories underlying brain activity. To date, the feasibility of combining optogenetic stimulation with fMRS has not been explored. We used green laser stimulation delivered through an optical fiber implanted superficially above the primary somatosensory forelimb cortex (S1FL) of rats expressing the C1V1 opsin in excitatory neurons. A protocol for the acquisition of functional 1H MR spectra upon optogenetic stimulation without craniotomy‐induced artefacts was established. Quantification of metabolite concentrations in S1FL upon optogenetic and electrical forepaw stimulation demonstrated significantly increased glutamate levels (+8.8% and +9.9%, p < 0.05 respectively), which were compensated by decreased glutamine levels (−17% and −18%, p < 0.05 respectively). Our results demonstrate for the first time the feasibility of combining optogenetic control and functional MR spectroscopy (o‐fMRS) in the rat somatosensory cortex, opening new possibilities for monitoring the energetic demands of specific cell populations and for exploring the underpinnings of energy metabolism during brain activity. Open Science Badges This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Probing activation‐induced neurochemical changes using optogenetics combined with functional magnetic resonance spectroscopy: a feasibility study in the rat primary somatosensory cortex

Just

Faber

2019

Journal of Neurochemistry

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“…MRI experiments were performed under light isoflurane anaesthesia, and image artifacts at the level of the hypothalamus could only be prevented by paralysis and mechanical ventilation (Grandjean et al, 2017;Sonnay et al, 2018). Despite efforts to improve image quality, responses within the ARC remained particularly sensitive to background noise, likely due to its proximity to the trachea.…”

Section: Discussionmentioning

confidence: 99%

“…BOLD fMRI time courses with minimal artifacts were obtained from mice under mechanical ventilation with pancuronium bromide-induced paralysis, as reported by others (Baltes et al, 2009). This also allowed us to lower isoflurane anaesthesia level to 0.7%, thus reducing its effects on cerebrovascular reactivity as in previous work (Sonnay et al, 2018).…”

Section: Glucose-induced Fmrimentioning

confidence: 98%

“…The ventilation rate was kept at 90 breaths per minute with a volume of 1.9-2.2 mL and 50% inspiration rate. Isoflurane level was then decreased to 0.7% (Sonnay et al, 2018), and the mice were then inserted into the MRI scanner. Body temperature was continuously monitored with a rectal temperature probe (SA Instruments, Stony Brook, NY, USA) and maintained at 36-37 °C with a warm water circulation system.…”

Section: Mri Experimentsmentioning

confidence: 99%

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A glucose-stimulated BOLD fMRI study of hypothalamic dysfunction in mice fed a high-fat and high-sucrose diet

Mohr

García-Serrano

Vieira

et al. 2020

Preprint

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Running headline: Hypothalamic fMRI in diet-induced obese miceAbbreviations: AgRP, agouti-related peptide; AMPK, AMP-activated protein kinase; ARC, arcuate nucleus; BOLD, blood oxygen level-dependent; CART, cocaine and amphetamine regulated transcript; CREB, cAMP response element-binding protein; DMN, dorsomedial nucleus; fMRI, functional magnetic resonance imaging; FOV, field of view; LH, lateral hypothalamus; MC4R, melanocortin 4 receptor; NPY, neuropeptide Y; POMC, pro-opiomelanocortin; PVN, paraventricular nucleus; T2D, type 2 diabetes; TE, echo time; TR, repetition time; VMN, ventromedial nucleus; VOI, volume of interest. AbstractThe hypothalamus is the central regulator of energy homeostasis. Hypothalamic neuronal circuits are disrupted upon overfeeding, and play a role in the development of metabolic disorders.While mouse models have been extensively employed for understanding mechanisms of hypothalamic dysfunction, functional magnetic resonance imaging (fMRI) on hypothalamic nuclei has been challenging. We implemented a robust glucose-induced fMRI paradigm that allows to repeatedly investigate hypothalamic responses to glucose. This approach was used to test the hypothesis that hypothalamic nuclei functioning is impaired in mice exposed to a high-fat and highsucrose diet (HFHSD) for 7 days. The blood oxygen level-dependent (BOLD) fMRI signal was measured from brains of mice under light isoflurane anaesthesia, during which a 2.6 g/kg glucose load was administered. The mouse hypothalamus responded to glucose but not saline administration with a biphasic BOLD fMRI signal reduction. Relative to controls, HFHSD-fed mice showed attenuated or blunted responses in arcuate nucleus, lateral hypothalamus, ventromedial nucleus and dorsomedial nucleus, but not in paraventricular nucleus. In sum, we have developed an fMRI paradigm that is able to determine dysfunction of glucose-sensing neuronal circuits within the mouse hypothalamus in a non-invasive manner.

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In vivo ¹³C and ¹H‐[¹³C] MRS studies of neuroenergetics and neurotransmitter cycling, applications to neurological and psychiatric disease and brain cancer

et al. 2019

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In the last 25 years 13 C MRS has been established as the only noninvasive method for measuring glutamate neurotransmission and cell specific neuroenergetics. Although technically and experimentally challenging 13 C MRS has already provided important new information on the relationship between neuroenergetics and neuronal function, the high energy cost of brain function in the resting state and the role of altered neuroenergetics and neurotransmitter cycling in disease. In this paper we review the metabolic and neurotransmitter pathways that can be measured by 13 C MRS and key findings on the linkage between neuroenergetics, neurotransmitter cycling, and brain function. Applications of 13 C MRS to neurological and psychiatric disease as well as brain cancer are reviewed. Recent technological developments that may help to overcome spatial resolution and brain coverage limitations of 13 C MRS are discussed. | INTRODUCTIONBrain cells are highly specialized metabolically and functionally. Prior to the advent of 13 C MRS there was no method of studying cell specific brain metabolism in vivo. As described in this review 13 C MRS in combination with selectively 13 C labeled substrates has allowed the study of how metabolism supports function in the three major brain cell types, glutamatergic neurons, GABAergic neurons, and glia. Glutamatergic neurons Abbreviations: ANLS, astrocyte neuronal lactate shuttle; ATP, adenosine tri phosphate; AV, arterio-venous; CMRglc (ox), cerebral metabolic rate of oxidative glucose consumption; CMRglc (ox)-N, cerebral metabolic rate of neuronal oxidative glucose consumption; CMRglc, cerebral metabolic rate of glucose consumption; DMI, deuterium metabolic imaging; EEG, electroencephalogram;GABA, gamma amino butyric acid; GBM, glioblastoma; HSQC, heteronuclear single quantum coherence; MDD, major depressive disorder; MRS, magnetic resonance spectroscopy; MRSI, magnetic resonance spectroscopic imaging; NMDA, N methyl D aspartate; nOe, nuclear Overhauser effect; PET, positron emission tomography; SAR, specific absorption rate; T1DM, type 1 diabetes mellitus; TCA, tricarboxylic acid cycle; Vcycle, Velocity (flux) of the glutamate/GABA/glutamine cycle.; VTCA, velocity of the tricarboxylic acid cycle release the major excitatory neurotransmitter glutamate and GABAergic neurons release the major inhibitory neurotransmitter gamma amino butyric acid (GABA). Information transfer in the brain is largely coded by the pattern and timing of glutamate and GABA neurotransmitter release in vesicles with glutamate release leading to depolarization at the postsynaptic terminal and GABA release leading to hyperpolarization 1 . As described in this review, studies primarily using 13 C MRS have shown that the energy required to support neuronal signaling is the dominant energy cost of the brain even under resting awake conditions. The large majority of glutamate and a significant fraction of GABA is taken up by a class of cells called glia. Glia are not directly involved in brain communication but are critical f...

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Astrocytic and neuronal oxidative metabolism are coupled to the rate of glutamate–glutamine cycle in the tree shrew visual cortex

Cited by 49 publications

References 68 publications

Probing activation‐induced neurochemical changes using optogenetics combined with functional magnetic resonance spectroscopy: a feasibility study in the rat primary somatosensory cortex

Probing activation‐induced neurochemical changes using optogenetics combined with functional magnetic resonance spectroscopy: a feasibility study in the rat primary somatosensory cortex

A glucose-stimulated BOLD fMRI study of hypothalamic dysfunction in mice fed a high-fat and high-sucrose diet

In vivo ¹³C and ¹H‐[¹³C] MRS studies of neuroenergetics and neurotransmitter cycling, applications to neurological and psychiatric disease and brain cancer

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Astrocytic and neuronal oxidative metabolism are coupled to the rate of glutamate–glutamine cycle in the tree shrew visual cortex

Cited by 49 publications

References 68 publications

Probing activation‐induced neurochemical changes using optogenetics combined with functional magnetic resonance spectroscopy: a feasibility study in the rat primary somatosensory cortex

Probing activation‐induced neurochemical changes using optogenetics combined with functional magnetic resonance spectroscopy: a feasibility study in the rat primary somatosensory cortex

A glucose-stimulated BOLD fMRI study of hypothalamic dysfunction in mice fed a high-fat and high-sucrose diet

In vivo 13C and 1H‐[13C] MRS studies of neuroenergetics and neurotransmitter cycling, applications to neurological and psychiatric disease and brain cancer

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In vivo ¹³C and ¹H‐[¹³C] MRS studies of neuroenergetics and neurotransmitter cycling, applications to neurological and psychiatric disease and brain cancer