Journal
GLIA
Volume 66, Issue 9, Pages 2013-2023Publisher
WILEY
DOI: 10.1002/glia.23454
Keywords
astrocytes; BOLD; fMRI; imaging mass spectrometry; optogenetics
Categories
Funding
- Takeda Science Foundation
- JSPS KAKENHI [25430011, 25115726, 15KT0111, 16H01620, 16K07032, 24111551, 26290021, 16H06145]
- Brain/MINDS
- Strategic Research Program for Brain Sciences (SRPBS) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (MEXT)
- Japan Agency for Medical Research and Development (AMED)
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Functional magnetic resonance imaging (fMRI) based on the blood oxygenation level-dependent (BOLD) signal has been used to infer sites of neuronal activation in the brain. A recent study demonstrated, however, unexpected BOLD signal generation without neuronal excitation, which led us to hypothesize the presence of another cellular source for BOLD signal generation. Collective assessment of optogenetic activation of astrocytes or neurons, fMRI in awake mice, electrophysiological measurements, and histochemical detection of neuronal activation, coherently suggested astrocytes as another cellular source. Unexpectedly, astrocyte-evoked BOLD signal accompanied oxygen consumption without modulation of neuronal activity. Imaging mass spectrometry of brain sections identified synthesis of acetyl-carnitine via oxidative glucose metabolism at the site of astrocyte-, but not neuron-evoked BOLD signal. Our data provide causal evidence that astrocytic activation alone is able to evoke BOLD signal response, which may lead to reconsideration of current interpretation of BOLD signal as a marker of neuronal activation.
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