Circuit-specific control of the medial entorhinal inputs to the dentate gyrus by atypical presynaptic NMDARs activated by astrocytes.
Fiche du document
2 juillet 2019
- doi: 10.1073/pnas.1816013116
- issn: 0027-8424
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.1816013116
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/pmid/31152131
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/eissn/1091-6490
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_0C799416BD3C7
info:eu-repo/semantics/openAccess , CC BY-NC-ND 4.0 , https://creativecommons.org/licenses/by-nc-nd/4.0/
Sujets proches
Glia (Neurology)Citer ce document
I. Savtchouk et al., « Circuit-specific control of the medial entorhinal inputs to the dentate gyrus by atypical presynaptic NMDARs activated by astrocytes. », Serveur académique Lausannois, ID : 10.1073/pnas.1816013116
Métriques
Partage / Export
Résumé
Here, we investigated the properties of presynaptic N-methyl-d-aspartate receptors (pre-NMDARs) at corticohippocampal excitatory connections between perforant path (PP) afferents and dentate granule cells (GCs), a circuit involved in memory encoding and centrally affected in Alzheimer's disease and temporal lobe epilepsy. These receptors were previously reported to increase PP release probability in response to gliotransmitters released from astrocytes. Their activation occurred even under conditions of elevated Mg 2+ and lack of action potential firing in the axons, although how this could be accomplished was unclear. We now report that these pre-NMDARs contain the GluN3a subunit conferring them low Mg 2+ sensitivity. GluN3a-containing NMDARs at PP-GC synapses are preponderantly presynaptic vs. postsynaptic and persist beyond the developmental period. Moreover, they are expressed selectively at medial-not lateral-PP axons and act to functionally enhance release probability specifically of the medial perforant path (MPP) input to GC dendrites. By controlling release probability, GluN3a-containing pre-NMDARs also control the dynamic range for long-term potentiation (LTP) at MPP-GC synapses, an effect requiring Ca 2+ signaling in astrocytes. Consistent with the functional observations, GluN3a subunits in MPP terminals are localized at sites away from the presynaptic release sites, often facing astrocytes, in line with a primary role for astrocytic inputs in their activation. Overall, GluN3A-containing pre-NMDARs emerge as atypical modulators of dendritic computations in the MPP-GC memory circuit.