Depolarization-induced suppression of excitation in murine autaptic hippocampal neurones

J Physiol. 2005 Dec 1;569(Pt 2):501-17. doi: 10.1113/jphysiol.2005.091918. Epub 2005 Sep 22.


Depolarization-induced suppression of excitation and inhibition (DSE and DSI) appear to be important forms of short-term retrograde neuronal plasticity involving endocannabinoids (eCB) and the activation of presynaptic cannabinoid CB1 receptors. We report here that CB1-dependent DSE can be elicited from autaptic cultures of excitatory mouse hippocampal neurones. DSE in autaptic cultures is both more robust and elicited with a more physiologically relevant stimulus than has been thus far reported for conventional hippocampal cultures. An additional requirement for autaptic DSE is filled internal calcium stores. Pharmacological experiments favour a role for 2-arachidonyl glycerol (2-AG) rather than arachidonyl ethanolamide (AEA) or noladin ether as the relevant endocannabinoid to elicit DSE. In particular, the latter two compounds fail to reversibly inhibit EPSCs, a quality inconsistent with the role of bona fide eCB mediating DSE. Delta9-Tetrahydrocannabinol (delta9-THC) fails to inhibit EPSCs, yet readily occludes both DSE and EPSC inhibition by a synthetic CB1 agonist, WIN 55212-2. With long-term exposure (approximately 18 h), delta9-THC also desensitizes CB1 receptors. Lastly, a functional endocannabinoid transporter is necessary for the expression of DSE.

Publication types

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

MeSH terms

  • Animals
  • Arachidonic Acids / pharmacology
  • Benzoxazines
  • Calcium / physiology
  • Cannabinoid Receptor Modulators / metabolism
  • Cannabinoid Receptor Modulators / physiology
  • Cells, Cultured
  • Dronabinol / pharmacology
  • Endocannabinoids
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology*
  • Glutamic Acid / physiology
  • Glycerides / pharmacology
  • Hippocampus / cytology
  • Hippocampus / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Morpholines / pharmacology
  • Naphthalenes / pharmacology
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology*
  • Neurons / metabolism
  • Neurons / physiology*
  • Nitric Oxide / physiology
  • Patch-Clamp Techniques
  • Polyunsaturated Alkamides
  • Receptor, Cannabinoid, CB1 / antagonists & inhibitors
  • Receptor, Cannabinoid, CB1 / physiology


  • Arachidonic Acids
  • Benzoxazines
  • Cannabinoid Receptor Modulators
  • Endocannabinoids
  • Glycerides
  • Morpholines
  • Naphthalenes
  • Polyunsaturated Alkamides
  • Receptor, Cannabinoid, CB1
  • noladin ether
  • Nitric Oxide
  • Glutamic Acid
  • (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
  • Dronabinol
  • glyceryl 2-arachidonate
  • Calcium
  • anandamide