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J Physiol. 2005 Dec 1;569(Pt 2):501-17. Epub 2005 Sep 22.

Depolarization-induced suppression of excitation in murine autaptic hippocampal neurones.

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Department of Anaesthesiology, University of Washington, Seattle, WA 98195, USA.


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.

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