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

Chiayu Q. Chiu, Pablo E. Castillo

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


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
Issue number1
StatePublished - Jan 2008


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

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience


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