Endocannabinoids potentiate synaptic transmission through stimulation of astrocytes

Neuron. 2010 Oct 6;68(1):113-26. doi: 10.1016/j.neuron.2010.08.043.

Abstract

Endocannabinoids and their receptor CB1 play key roles in brain function. Astrocytes express CB1Rs that are activated by endocannabinoids released by neurons. However, the consequences of the endocannabinoid-mediated neuron-astrocyte signaling on synaptic transmission are unknown. We show that endocannabinoids released by hippocampal pyramidal neurons increase the probability of transmitter release at CA3-CA1 synapses. This synaptic potentiation is due to CB1R-induced Ca(2+) elevations in astrocytes, which stimulate the release of glutamate that activates presynaptic metabotropic glutamate receptors. While endocannabinoids induce synaptic depression in the stimulated neuron by direct activation of presynaptic CB1Rs, they indirectly lead to synaptic potentiation in relatively more distant neurons by activation of CB1Rs in astrocytes. Hence, astrocyte calcium signal evoked by endogenous stimuli (neuron-released endocannabinoids) modulates synaptic transmission. Therefore, astrocytes respond to endocannabinoids that then potentiate synaptic transmission, indicating that astrocytes are actively involved in brain physiology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Astrocytes / physiology*
  • Benzoates / pharmacology
  • Biophysics
  • Calcium / metabolism
  • Cannabinoid Receptor Modulators / antagonists & inhibitors
  • Cannabinoid Receptor Modulators / metabolism*
  • Cannabinoid Receptor Modulators / pharmacology
  • Chelating Agents / pharmacology
  • Drug Interactions
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Electric Stimulation / methods
  • Endocannabinoids*
  • Enzyme Inhibitors / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / genetics
  • Glycine / analogs & derivatives
  • Glycine / pharmacology
  • Hippocampus / cytology
  • In Vitro Techniques
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Patch-Clamp Techniques / methods
  • Photolysis
  • Piperidines / pharmacology
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / physiology*
  • Pyrazoles / pharmacology
  • Pyridines / pharmacology
  • Receptor, Cannabinoid, CB1 / deficiency
  • Resorcinols / pharmacology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / genetics
  • Synaptic Transmission / physiology*
  • Thapsigargin / pharmacology

Substances

  • Benzoates
  • Cannabinoid Receptor Modulators
  • Chelating Agents
  • Endocannabinoids
  • Enzyme Inhibitors
  • Excitatory Amino Acid Antagonists
  • Piperidines
  • Pyrazoles
  • Pyridines
  • Receptor, Cannabinoid, CB1
  • Resorcinols
  • alpha-methyl-4-carboxyphenylglycine
  • AM 251
  • Egtazic Acid
  • 3,5-dihydroxyphenylglycine
  • Thapsigargin
  • 6-methyl-2-(phenylethynyl)pyridine
  • 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
  • Calcium
  • Glycine