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

NEUROPHARMACOLOGY

卷:153

Article

Penasco, Sara^1,2  Rico-Barrio, Irantzu^1,2  Puente, Nagore^1,2  Maria Gomez-Urquijo, Sonia^1,2  Fontaine, Christine J.³  Egana-Huguet, Jon^1,2  Achicallende, Svein^1,2  Ramos, Almudena^1,2  Reguero, Leire^1,2  Elezgarai, Izaskun^1,2  Nahirney, Patrick C.³  Christie, Brian R.³  Grandes, Pedro^1,2,3 

[1] Univ Basque Country UPV EHU, Dept Neurosci, Fac Med & Nursing, Barrio Sarriena S-N, E-48940 Leioa, Spain

[2] Univ Basque Country UPV EHU, Achucarro Basque Ctr Neurosci, Sci Pk, E-48940 Leioa, Spain

[3] Univ Victoria, Div Med Sci, Victoria, BC V8P 5C2, Canada

关键词: CB, receptor;    2-AG;    Electrophysiology;    Excitatory synapses;    Long-term depression;    Hippocampus;   

DOI  :  10.1016/j.neuropharm.2019.04.020

来源: Elsevier

【 摘 要 】

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 similar to 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 CB, 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.

【 授权许可】

Free