ArticleThe Journal of physiology2011
Genetic deletion of monoacylglycerol lipase alters endocannabinoid-mediated retrograde synaptic depression in the cerebellum.
Article in The Journal of physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 63 citations in OpenAlex.
- FAAH and MAGL inhibition: Evolving approaches to treating substance use disorders.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Circuit mechanisms governing endocannabinoid modulation of affective behaviour and stress adaptation.Nature reviews. Neuroscience · 2025Review
- The endocannabinoid system as a putative target for the development of novel drugs for the treatment of psychiatric illnesses.Psychological medicine · 2023Review
- Imaging and Genetic Tools for the Investigation of the Endocannabinoid System in the CNS.International journal of molecular sciences · 2023Review
- Mechanisms of endocannabinoid transport in the brain.British journal of pharmacology · 2022Review
- A potent and selective inhibitor for the modulation of MAGL activity in the neurovasculature.PloS one · 2022Article
- Alpha/Beta-Hydrolase Domain-Containing 6: Signaling and Function in the Central Nervous System.Frontiers in pharmacology · 2021Review
- Endocannabinoid-Mediated Control of Neural Circuit Excitability and Epileptic Seizures.Frontiers in neural circuits · 2021Review
- Endocannabinoid-Epigenetic Cross-Talk: A Bridge toward Stress Coping.International journal of molecular sciences · 2020Review
- Distinctive Evidence Involved in the Role of Endocannabinoid Signalling in Parkinson's Disease: A Perspective on Associated Therapeutic Interventions.International journal of molecular sciences · 2020Review
- Monoacylglycerol lipase inhibitors: modulators for lipid metabolism in cancer malignancy, neurological and metabolic disorders.Acta pharmaceutica Sinica. B · 2020Review
- Druggable Targets in Endocannabinoid Signaling.Advances in experimental medicine and biology · 2020Review
- Long-term depression of presynaptic cannabinoid receptor function at parallel fibre synapses.The Journal of physiology · 2019Article
- Biochemical and Proteomic Characterization of Recombinant Human α/β Hydrolase Domain 6.Scientific reports · 2019Article
- Involvement of TRPV1 Channels in Energy Homeostasis.Frontiers in endocrinology · 2018Review
- Coordinated regulation of endocannabinoid-mediated retrograde synaptic suppression in the cerebellum by neuronal and astrocytic monoacylglycerol lipase.Scientific reports · 2016Article
- Molecular characterization of human ABHD2 as TAG lipase and ester hydrolase.Bioscience reports · 2016Article
- α/β-Hydrolase domain-containing 6 (ABHD6) negatively regulates the surface delivery and synaptic function of AMPA receptors.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Porcupine Controls Hippocampal AMPAR Levels, Composition, and Synaptic Transmission.Cell reports · 2016Article
- Metabolic Interplay between Astrocytes and Neurons Regulates Endocannabinoid Action.Cell reports · 2015Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
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 α-β-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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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.