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

Neuropharmacology. 2008 Jan;54(1):68-78. doi: 10.1016/j.neuropharm.2007.06.026. Epub 2007 Jul 6.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Animals, Newborn
  • Arachidonic Acids / metabolism
  • Benzoxazines / pharmacology
  • Calcium / metabolism
  • Calcium Channel Blockers / pharmacology
  • Cannabinoid Receptor Modulators / metabolism*
  • Cholinergic Agents / pharmacology
  • Dentate Gyrus / cytology*
  • Electric Stimulation
  • Endocannabinoids*
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology*
  • Excitatory Postsynaptic Potentials / radiation effects
  • Glycerides / metabolism
  • In Vitro Techniques
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Morpholines / pharmacology
  • Naphthalenes / pharmacology
  • Neural Pathways / physiology
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology*
  • Neuronal Plasticity / radiation effects
  • Neurons / physiology*
  • Patch-Clamp Techniques
  • Rats
  • Rats, Wistar
  • Receptor, Cannabinoid, CB1 / deficiency
  • Receptor, Cannabinoid, CB1 / physiology


  • Arachidonic Acids
  • Benzoxazines
  • Calcium Channel Blockers
  • Cannabinoid Receptor Modulators
  • Cholinergic Agents
  • Endocannabinoids
  • Glycerides
  • Morpholines
  • Naphthalenes
  • Receptor, Cannabinoid, CB1
  • (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
  • glyceryl 2-arachidonate
  • Calcium