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TitleStress gates an astrocytic energy reservoir to impair synaptic plasticity.
Publication TypeJournal Article
Year of Publication2020
AuthorsMurphy-Royal, Ciaran, April D. Johnston, Andrew K. J. Boyce, Blanca Diaz-Castro, Adam Institoris, Govind Peringod, Oliver Zhang, Randy F. Stout, David C. Spray, Roger J. Thompson, Baljit S. Khakh, Jaideep S. Bains, and Grant R. Gordon
JournalNat Commun
Volume11
Issue1
Pagination2014
Date Published2020 04 24
ISSN2041-1723
KeywordsAdaptation, Psychological, Animals, Astrocytes, Disease Models, Animal, Energy Metabolism, Female, Glucose, Hippocampus, Humans, Lactic Acid, Long-Term Potentiation, Male, Metabolic Networks and Pathways, Mice, Neocortex, Neurons, Patch-Clamp Techniques, Stress, Psychological
Abstract

Astrocytes support the energy demands of synaptic transmission and plasticity. Enduring changes in synaptic efficacy are highly sensitive to stress, yet whether changes to astrocyte bioenergetic control of synapses contributes to stress-impaired plasticity is unclear. Here we show in mice that stress constrains the shuttling of glucose and lactate through astrocyte networks, creating a barrier for neuronal access to an astrocytic energy reservoir in the hippocampus and neocortex, compromising long-term potentiation. Impairing astrocytic delivery of energy substrates by reducing astrocyte gap junction coupling with dominant negative connexin 43 or by disrupting lactate efflux was sufficient to mimic the effects of stress on long-term potentiation. Furthermore, direct restoration of the astrocyte lactate supply alone rescued stress-impaired synaptic plasticity, which was blocked by inhibiting neural lactate uptake. This gating of synaptic plasticity in stress by astrocytic metabolic networks indicates a broader role of astrocyte bioenergetics in determining how experience-dependent information is controlled.

DOI10.1038/s41467-020-15778-9
Alternate JournalNat Commun
PubMed ID32332733
PubMed Central IDPMC7181611
Grant List / / CIHR / Canada