ArticleProceedings of the National Academy of Sciences of the United States of America2012
Synapse type-independent degradation of the endocannabinoid 2-arachidonoylglycerol after retrograde synaptic suppression.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 50 citations in OpenAlex.
- Article
- Distribution and subacute modulation of endocannabinoid metabolizing enzymes in the trigeminal complex and midbrain in a pre-clinical model of post-traumatic headache.The journal of headache and pain · 2026Article
- Circuit mechanisms governing endocannabinoid modulation of affective behaviour and stress adaptation.Nature reviews. Neuroscience · 2025Review
- Impact of Elovl5 Deficiency on Cerebellar Excitatory Synaptic Transmission in Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Imaging and Genetic Tools for the Investigation of the Endocannabinoid System in the CNS.International journal of molecular sciences · 2023Review
- Roles of the Cannabinoid System in the Basal Ganglia in Parkinson's Disease.Frontiers in cellular neuroscience · 2022Review
- Diacylglycerol Lipase-β Knockout Mice Display a Sex-Dependent Attenuation of Traumatic Brain Injury-Induced Mortality with No Impact on Memory or Other Functional Consequences.Cannabis and cannabinoid research · 2021Article
- Endocannabinoid-Mediated Control of Neural Circuit Excitability and Epileptic Seizures.Frontiers in neural circuits · 2021Review
- Control of excessive neural circuit excitability and prevention of epileptic seizures by endocannabinoid signaling.Cellular and molecular life sciences : CMLS · 2018Review
- Monoglyceride lipase as a drug target: At the crossroads of arachidonic acid metabolism and endocannabinoid signaling.Pharmacology & therapeutics · 2017Review
- Coordinated regulation of endocannabinoid-mediated retrograde synaptic suppression in the cerebellum by neuronal and astrocytic monoacylglycerol lipase.Scientific reports · 2016Article
- Does modulation of the endocannabinoid system have potential therapeutic utility in cerebellar ataxia?The Journal of physiology · 2016Review
- Article
- Metabolic Interplay between Astrocytes and Neurons Regulates Endocannabinoid Action.Cell reports · 2015Article
- Impaired 2-AG Signaling in Hippocampal Glutamatergic Neurons: Aggravation of Anxiety-Like Behavior and Unaltered Seizure Susceptibility.The international journal of neuropsychopharmacology · 2015Article
- Weeding out bad waves: towards selective cannabinoid circuit control in epilepsy.Nature reviews. Neuroscience · 2015Review
- Promising cannabinoid-based therapies for Parkinson's disease: motor symptoms to neuroprotection.Molecular neurodegeneration · 2015Review
- VGluT3-expressing CCK-positive basket cells construct invaginating synapses enriched with endocannabinoid signaling proteins in particular cortical and cortex-like amygdaloid regions of mouse brains.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Task-specific enhancement of hippocampus-dependent learning in mice deficient in monoacylglycerol lipase, the major hydrolyzing enzyme of the endocannabinoid 2-arachidonoylglycerol.Frontiers in behavioral neuroscience · 2015Article
- Fever Is Mediated by Conversion of Endocannabinoid 2-Arachidonoylglycerol to Prostaglandin E2.PloS one · 2015Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The endocannabinoid 2-arachidonoylglycerol (2-AG) mediates retrograde synaptic suppression. Although the mechanisms of 2-AG production are well characterized, how 2-AG is degraded is less clearly understood. Here we found that expression of the 2-AG hydrolyzing enzyme monoacylglycerol lipase (MGL) was highly heterogeneous in the cerebellum, being rich within parallel fiber (PF) terminals, weak in Bergman glia (BG), and absent in other synaptic terminals. Despite this highly selective MGL expression pattern, 2-AG-mediated retrograde suppression was significantly prolonged at not only PF-Purkinje cell (PC) synapses but also climbing fiber-PC synapses in granule cell-specific MGL knockout (MGL-KO) mice whose cerebellar MGL expression was confined to the BG. Virus-mediated expression of MGL into the BG of global MGL-KO mice significantly shortened 2-AG-mediated retrograde suppression at PF-PC synapses. Furthermore, contribution of MGL to termination of 2-AG signaling depended on the distance from MGL-rich PFs to inhibitory synaptic terminals. Thus, 2-AG is degraded in a synapse-type independent manner by MGL present in PFs and the BG. The results of the present study strongly suggest that MGL regulates 2-AG signaling rather broadly within a certain range of neural tissue, although MGL expression is heterogeneous and limited to a subset of nerve terminals and astrocytes.
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Registered trials
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.