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Cited by 79Neuroscience and Neuropharmacology ResearchMemory and Neural MechanismsNeurogenesis and neuroplasticity mechanisms

Ultrastructural evidence for a role of astrocytes and glycogen-derived lactate in learning-dependent synaptic stabilization.

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Vezzoli, E, Calì, C, De Roo, M, Ponzoni, L, Sogne, E, Gagnon, N, Francolini, M, Braida, D +4 more·2020·Cerebral Cortex
DOI 10.1093/cercor/bhz226PMC PMC7174989
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Abstract

Long-term memory formation (LTM) is a process accompanied by energy-demanding structural changes at synapses and increased spine density. Concomitant increases in both spine volume and postsynaptic density (PSD) surface area have been suggested but never quantified in vivo by clear-cut experimental evidence. Using novel object recognition in mice as a learning task followed by 3D electron microscopy analysis, we demonstrate that LTM induced all aforementioned synaptic changes, together with an increase in the size of astrocytic glycogen granules, which are a source of lactate for neurons. The selective inhibition of glycogen metabolism in astrocytes impaired learning, affecting all the related synaptic changes. Intrahippocampal administration of l-lactate rescued the behavioral phenotype, along with spine density within 24 hours. Spine dynamics in hippocampal organotypic slices undergoing theta burst-induced long-term potentiation was similarly affected by inhibition of glycogen metabolism and rescued by l-lactate. These results suggest that learning primes astrocytic energy stores and signaling to sustain synaptic plasticity via l-lactate.

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  • Glycogen granules are a feature unique to astrocytes in the brain and can be used to identify astrocytes in electron microscopy.

    “The mitochondria analyzed were exclusively from cells containing glycogen granules in the cytoplasm, a feature unique to astrocytes in the brain. In electron microscopy images, glycogen appears as electron-dense, spherical granules within astrocytic processes (Phelps, 1972; Vezzoli et al., 2020).”

    From Aging promotes an increase in mitochondrial fragmentation in astrocytes (2024) · cites this paper as Vezzoli et al., 2020

  • Glycogen granules are exclusive to astrocytes within the central nervous system and serve as an energy reserve.

    “Glycogen granules are exclusive to astrocytes within the central nervous system and serve as an energy reserve, particularly important in regulating neuronal metabolismo (Phelps, 1972; Vezzoli et al., 2020)”

    From Aging promotes an increase in mitochondrial fragmentation in astrocytes (2024) · cites this paper as Vezzoli et al., 2020

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Authors
Vezzoli, E., Calì, C., De Roo, M., Ponzoni, L., Sogne, E., Gagnon, N., Francolini, M., Braida, D., Sala, M., Muller, D., Falqui, A., & Magistretti, P. J.
Affiliations
  • University of Milan (IT)
  • King Abdullah University of Science and Technology (SA)
  • Department of Basic Neuroscience, University of Geneva Medical School, 1206 Geneva, Switzerland
  • CNR, Institute of Neuroscience, 20129 Milano, Italy
Corresponding author
  • Falqui, A
  • Magistretti, P J
ORCID
Venue
Cerebral Cortex
Publisher
Oxford University Press (OUP)
Published
2019-12-06
Volume
30
Issue
4
Pages
2114-2127
ISSN
  • 1047-3211 (ISSN-L)
  • 1460-2199
DOI
10.1093/cercor/bhz226
PMC
PMC7174989
OpenAlex
W2993751077
Cited by
79
References
8
Citations by year
2026: 8 · 2025: 14 · 2024: 16 · 2023: 15 · 2022: 4 · 2021: 12 · 2020: 10
FWCI
3.11
Type
journal article
Language
en
Open access
Licence
Locations
  • Cerebral Cortex (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, cc-by-nc)
  • Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
  • King Abdullah University of Science and Technology Repository (King Abdullah University of Science and Technology) (submittedVersion, other-oa)
Funders
  • KAUST-EPFL Alliance for Brain Energy Metabolism
  • KAUST Baseline
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords
astrocytes, glycogen metabolism, lactate, long-term memory, synaptic plasticity, dendritic spines, postsynaptic density, hippocampus, novel object recognition, L-lactate, theta burst stimulation, long-term potentiation, astrocyte-neuron communication, synaptic stabilization
MeSH terms
Animals, Astrocytes, Glycogen, Hippocampus, Learning, Male, Mice, Inbred C57BL, Organ Culture Techniques, Synapses, Lactic Acid, Mice

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