Input-specific plasticity at excitatory synapses mediated by endocannabinoids in the dentate gyrus

Chiayu Q. Chiu, Pablo E. Castillo

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Endocannabinoids (eCBs) mediate transient and long-lasting synaptic plasticity in several brain structures. In the dentate gyrus, activation of the type 1 cannabinoid receptor (CB1R) by exogenous ligands reportedly depresses excitatory synaptic transmission. However, direct evidence of eCB signaling at excitatory synapses in this region has been lacking. Here, we demonstrate that eCB release can be induced by a brief postsynaptic depolarization of dentate granule cells (DGCs), which potently and transiently suppresses glutamatergic inputs from mossy cell interneurons (MCs) but not from entorhinal cortex via the lateral and medial perforant paths. This input-specific depolarization-induced suppression of excitation (DSE) is calcium-dependent and can be modulated by agonists of cholinergic and group I metabotropic glutamate receptors. Inhibiting the synthesis of 2-arachidonoyl glycerol (2-AG), one of the most abundant eCBs in the brain, by diacyglycerol lipase (DGL) does not abolish DSE. Moreover, preventing the breakdown of anandamide, the other main eCB, does not potentiate DSE. Thus, eCB signaling underlying DSE in the dentate does not require DGL activity and is unlikely to be mediated by anandamide. Finally, we find that manipulations known to induce eCB-LTD at other central synapses do not trigger LTD at MCF-DGC synapses.

Original languageEnglish (US)
Pages (from-to)68-78
Number of pages11
JournalNeuropharmacology
Volume54
Issue number1
DOIs
StatePublished - Jan 2008

Fingerprint

Endocannabinoids
Dentate Gyrus
Synapses
Lipase
Perforant Pathway
Cholinergic Agonists
Cannabinoid Receptors
Entorhinal Cortex
Metabotropic Glutamate Receptors
Neuronal Plasticity
Brain
Interneurons
Synaptic Transmission
Ligands
Calcium
anandamide

Keywords

  • CB1 receptors
  • DSE
  • Endocannabinoids
  • Excitatory synaptic transmission
  • Glutamatergic inputs
  • Mossy cells

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology

Cite this

Input-specific plasticity at excitatory synapses mediated by endocannabinoids in the dentate gyrus. / Chiu, Chiayu Q.; Castillo, Pablo E.

In: Neuropharmacology, Vol. 54, No. 1, 01.2008, p. 68-78.

Research output: Contribution to journalArticle

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