Lactate from astrocytes fuels learning-induced mRNA translation in excitatory and inhibitory neurons
Open accessAbstract
Glycogenolysis and lactate transport from astrocytes to neurons is required for long-term memory formation, but the role of this lactate is poorly understood. Here we show that the Krebs cycle substrates pyruvate and ketone body B3HB can functionally replace lactate in rescuing memory impairment caused by inhibition of glycogenolysis or expression knockdown of glia monocarboxylate transporters (MCTs) 1 and 4 in the dorsal hippocampus of rats. In contrast, either metabolite is unable to rescue memory impairment produced by expression knockdown of MCT2, which is selectively expressed by neurons, indicating that a critical role of astrocytic lactate is to provide energy for neuronal responses required for long-term memory. These responses include learning-induced mRNA translation in both excitatory and inhibitory neurons, as well as expression of Arc/Arg3.1. Thus, astrocytic lactate acts as an energy substrate to fuel learning-induced de novo neuronal translation critical for long-term memory.
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The metabolic responses to perceived, but not unperceived, sensory stimulation could be enabling factors for learning and memory.
“As such, the metabolic responses to perceived, but not unperceived, sensory stimulation could be enabling factors for learning and memory”
From Perception is associated with the brain’s metabolic response to sensory stimulation (2022) · cites this paper as Descalzi et al., 2019
The Introduction links learning-related metabolism to memory formation, and the Discussion proposes a role for aerobic glycolysis in learning and memory. Neither section distinguishes perceived from unperceived sensory stimulation, so the claimed contrast is not supported by this paper. Page numbers were not available in our copy. (LLM, conf=0.86)
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Self-citation
- Authors
- Descalzi, G., Gao, V., Steinman, M. Q., Suzuki, A., & Alberini, C. M.
- Affiliations
- New York University (US)
- University of Toyama (JP)
- Corresponding author
- Alberini, Cristina M.
- Venue
- Communications Biology
- Published
- 2019-07-02
- Volume
- 2
- Issue
- 1
- Pages
- 247-247
- ISSN
- 2399-3642 (ISSN-L)
- PMC
- PMC6606643
- OpenAlex
- W2954464051
- Cited by
- 188
- References
- 69
- Citations by year
- 2026: 29 · 2025: 31 · 2024: 31 · 2023: 24 · 2022: 27 · 2021: 27 · 2020: 19
- FWCI
- 10.61
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Communications Biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (MH100822)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- astrocyte-neuron lactate shuttle, long-term memory, pyruvate, ketone bodies, glycogenolysis, monocarboxylate transporters, MCT1, MCT2, MCT4, hippocampus, Arc/Arg3.1, neuronal energy metabolism, excitatory neurons, inhibitory neurons
- MeSH terms
- Memory Consolidation, Animals, Astrocytes, Avoidance Learning, Brain, Citric Acid Cycle, Gangliosides, Hippocampus, Male, Memory Disorders, Neurons, RNA, Messenger, Pyruvic Acid, Lactic Acid, Rats, Long-Evans, Monocarboxylic Acid Transporters, Glycogenolysis, Rats, Memory, Episodic
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