Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis
Abstract
We have found that two-photon fluorescence imaging of nicotinamide adenine dinucleotide (NADH) provides the sensitivity and spatial three-dimensional resolution to resolve metabolic signatures in processes of astrocytes and neurons deep in highly scattering brain tissue slices. This functional imaging reveals spatiotemporal partitioning of glycolytic and oxidative metabolism between astrocytes and neurons during focal neural activity that establishes a unifying hypothesis for neurometabolic coupling in which early oxidative metabolism in neurons is eventually sustained by late activation of the astrocyte-neuron lactate shuttle. Our model integrates existing views of brain energy metabolism and is in accord with known macroscopic physiological changes in vivo.
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Upon stimulation of neurons in a brain slice or individual dissociated neurons, the NAD(P)H signal has a stereotyped response: a rapid dip in fluorescence within the first few seconds that yields in ∼10 s to a prolonged increase above baseline (overshoot) lasting for 2-3 min.
“Upon stimulation of neurons in a brain slice (Kann et al., 2003; Shuttleworth et al., 2003; Kasischke et al., 2004) or individual dissociated neurons (Duchen, 1992), the NAD(P)H signal has a stereotyped response: a rapid dip in fluorescence occurring within the first few seconds that yields in ∼10 s to a prolonged increase above baseline (overshoot) lasting for 2–3 min (Fig. 2 B).”
From Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism (2018) · cites this paper as Kasischke et al., 2004
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- Authors
- Kasischke, K. A., Vishwasrao, H. D., Fisher, P. J., Zipfel, W. R., & Webb, W. W.
- Affiliations
- Cornell University (US)
- Corresponding author
- Webb, Watt W.
- Venue
- Science
- Published
- 2004-07-02
- Volume
- 305
- Issue
- 5680
- Pages
- 99-103
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2143647842
- Cited by
- 742
- References
- 29
- Citations by year
- 2026: 9 · 2025: 21 · 2024: 17 · 2023: 15 · 2022: 18 · 2021: 25 · 2020: 14 · 2019: 22 · 2018: 31 · 2017: 29 · 2016: 36 · 2015: 32 · 2014: 33 · 2013: 35 · 2012: 41
- FWCI
- 21.80
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Biomedical Imaging and Bioengineering (P41EB001976, P41-EB001976-16)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Optical Imaging and Spectroscopy Techniques
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Keywords
- neurometabolic coupling, astrocyte-neuron lactate shuttle, brain energy metabolism, astrocytes, neurons, lactate metabolism
- MeSH terms
- Animals, Astrocytes, Citric Acid Cycle, Cytoplasm, Dendrites, Electron Transport, Fluorescence, Glycolysis, Hippocampus, Mitochondria, NAD, Neurons, Oxidation-Reduction, Oxygen Consumption, Spectrometry, Fluorescence, Rats, Sprague-Dawley, Pyramidal Cells, Lactic Acid, Rats, In Vitro Techniques
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