Endocannabinoid long-term depression revealed at medial perforant path excitatory synapses in the dentate gyrus

The endocannabinoid system modulates synaptic plasticity in the hippocampus, but a link between long-term synaptic plasticity and the type 1 cannabinoid (CB1) receptor at medial perforant path (MPP) synapses remains elusive. Here, immuno-electron microscopy in adult mice showed that ∼26% of the exci...

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Bibliographic Details
Published in:Neuropharmacology
Main Authors: Peñasco, Sara, Rico-Barrio, Irantzu, Puente, Nagore, Gómez-Urquijo, Sonia María, Fontaine, Christine J., Egaña-Huguet, Jon, Achicallende, Svein, Ramos, Almudena, Reguero, Leire, Elezgarai, Izaskun, Nahirney, Patrick C., Christie, Brian R., Grandes, Pedro
Format: Article in Journal/Newspaper
Language:English
Published: Neuropharmacology 2019
Subjects:
CB1 receptor
2-AG
Electrophysiology
Excitatory synapses
Long-term depression
Hippocampus
Canada
DML
Online Access:http://hdl.handle.net/1828/10924
https://doi.org/10.1016/j.neuropharm.2019.04.020
Description
Summary:The endocannabinoid system modulates synaptic plasticity in the hippocampus, but a link between long-term synaptic plasticity and the type 1 cannabinoid (CB1) receptor at medial perforant path (MPP) synapses remains elusive. Here, immuno-electron microscopy in adult mice showed that ∼26% of the excitatory synaptic terminals in the middle 1/3 of the dentate molecular layer (DML) contained CB1 receptors, and field excitatory postsynaptic potentials evoked by MPP stimulation were inhibited by CB1 receptor activation. In addition, MPP stimulation at 10 Hz for 10 min triggered CB1 receptor-dependent excitatory long-term depression (eCB-eLTD) at MPP synapses of wild-type mice but not on CB1-knockout mice. This eCB-eLTD was group I mGluR-dependent, required intracellular calcium influx and 2-arachydonoyl-glycerol (2-AG) synthesis but did not depend on N-methyl-d-aspartate (NMDA) receptors. Overall, these results point to a functional role for CB1 receptors with eCB-eLTD at DML MPP synapses and further involve these receptors in memory processing within the adult brain. This work was supported by MINECO/FEDER, UE (grant number SAF2015-65034-R to PG); The Basque Government (grant number BCG IT764-13 to PG); Red de Trastornos Adictivos, Instituto de Salud Carlos III (ISC-III) and European Regional Development Funds-European Union (ERDF-EU; grant RD16/0017/0012 to PG); PhD contract from MINECO (BES-2013-065057 to SP); Vanier Canada Graduate Scholarship (NSERC to CJF). Faculty Reviewed

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