Zhong_2011_J.Physiol_589_4847

Reference

Title : Genetic deletion of monoacylglycerol lipase alters endocannabinoid-mediated retrograde synaptic depression in the cerebellum - Zhong_2011_J.Physiol_589_4847
Author(s) : Zhong P , Pan B , Gao XP , Blankman JL , Cravatt BF , Liu QS
Ref : Journal de Physiologie , 589 :4847 , 2011
Abstract : The endocannabinoid (eCB) 2-arachidonoylglycerol (2-AG) is hydrolysed primarily by monoacylglycerol lipase (MAGL). Here, we investigated whether eCB-mediated retrograde synaptic depression in cerebellar slices was altered in MAGL knockout (MAGL(-/-)) mice. Depolarization-induced suppression of excitation (DSE) and metabotropic glutamate receptor (mGluR1)-mediated synaptic depression are mediated by 2-AG-induced activation of CB(1) receptors. We show that genetic deletion of MAGL prolonged DSE at parallel fibre (PF) or climbing fibre (CF) to Purkinje cell (PC) synapses. Likewise, mGluR1-mediated synaptic depression, induced either by high-frequency stimulation of PF or mGluR1 agonist DHPG, was prolonged in MAGL(-/-) mice. About 15% of 2-AG in the brain is hydrolysed by serine hydrolase alpha-beta-hydrolase domain 6 and 12 (ABHD6 and ABHD12). However, the selective ABHD6 inhibitor WWL123 had no significant effect on cerebellar DSE in MAGL(+/+) and (-/-) mice. The CB(1) receptor antagonist SR141716 significantly increased the amplitude of basal excitatory postsynaptic currents (EPSCs) in MAGL(-/-) mice but not in MAGL(+/+) mice. Conversely, the CB(1) agonist WIN55212 induced less depression of basal EPSCs in MAGL(-/-) mice than in MAGL(+/+) mice. These results provide genetic evidence that inactivation of 2-AG by MAGL determines the time course of eCB-mediated retrograde synaptic depression and that genetic deletion of MAGL causes tonic activation and consequential desensitization of CB(1) receptors.
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PubMedID: 21911610
Gene_locus related to this paper: human-MGLL , mouse-MGLL

Related information

Gene_locus related to this paper: human-MGLL , mouse-MGLL

Citations formats

Zhong P, Pan B, Gao XP, Blankman JL, Cravatt BF, Liu QS (2011)
Genetic deletion of monoacylglycerol lipase alters endocannabinoid-mediated retrograde synaptic depression in the cerebellum
Journal de Physiologie 589 :4847

Zhong P, Pan B, Gao XP, Blankman JL, Cravatt BF, Liu QS (2011)
Journal de Physiologie 589 :4847