Depolarization-induced suppression of excitation in murine autaptic hippocampal neurones.
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.
Straiker
Alex
A
Department of Anaesthesiology, University of Washington, Seattle, WA 98195, USA. straiker@u.washington.edu
Mackie
Ken
K
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D048588:Benzoxazines; D002118:Calcium / Q000502:physiology; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism / Q000502:physiology; D002478:Cells, Cultured; D013759:Dronabinol / Q000494:pharmacology; D063388:Endocannabinoids; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D018698:Glutamic Acid / Q000502:physiology; D005989:Glycerides / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology; D018408:Patch-Clamp Techniques; D053284:Polyunsaturated Alkamides; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000502:physiology
D001095:Arachidonic Acids; D048588:Benzoxazines; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D005989:Glycerides; D009025:Morpholines; D009281:Naphthalenes; D053284:Polyunsaturated Alkamides; D043884:Receptor, Cannabinoid, CB1; C424442:noladin ether; D009569:Nitric Oxide; D018698:Glutamic Acid; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D013759:Dronabinol; C094503:glyceryl 2-arachidonate; D002118:Calcium; C078814:anandamide