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

Date

2019

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

Journal Title

Journal ISSN

Volume Title

Publisher

Neuropharmacology

Abstract

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.

Description

Keywords

CB1 receptor, 2-AG, Electrophysiology, Excitatory synapses, Long-term depression, Hippocampus

Citation

Peñasco , S., Rico-Barrio, I., Puente, N., Gómez-Urquijo, S.M., Fontaine, C.J., Egaña-Huguet, J., … Grandes, P. (2019). Endocannabinoid long-term depression revealed at medial perforant path excitatory synapses in the dentate gyrus. Neuropharmacology, 153, 32-40. https://doi.org/10.1016/j.neuropharm.2019.04.020