Stress gates an astrocytic energy reservoir to impair synaptic plasticity.
Adaptation, Psychological
/ physiology
Animals
Astrocytes
/ metabolism
Disease Models, Animal
Energy Metabolism
/ physiology
Female
Glucose
/ metabolism
Hippocampus
/ cytology
Humans
Lactic Acid
/ metabolism
Long-Term Potentiation
/ physiology
Male
Metabolic Networks and Pathways
/ physiology
Mice
Neocortex
/ cytology
Neurons
/ physiology
Patch-Clamp Techniques
Stress, Psychological
/ metabolism
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
24 04 2020
24 04 2020
Historique:
received:
14
02
2020
accepted:
26
03
2020
entrez:
26
4
2020
pubmed:
26
4
2020
medline:
11
8
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32332733
doi: 10.1038/s41467-020-15778-9
pii: 10.1038/s41467-020-15778-9
pmc: PMC7181611
doi:
Substances chimiques
Lactic Acid
33X04XA5AT
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2014Subventions
Organisme : CIHR
Pays : Canada
Commentaires et corrections
Type : ErratumIn
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