ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2005
Synaptically driven endocannabinoid release requires Ca2+-assisted metabotropic glutamate receptor subtype 1 to phospholipase Cbeta4 signaling cascade in the cerebellum.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers.
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Who cites it
127 citing papers in PubMed, 230 citations in OpenAlex.
- The Potential of Cannabidiol for the Treatment of Psychosis: Endocannabinoid Regulation of Serotonergic Neurotransmission via Serotonin 5-HT1A/2A Receptors.Neurochemical research · 2026Review
- Mechanisms and Cell Type-Dependence of Non-Hebbian Long-Term Potentiation at Primary Afferent Synapses in the Mouse Spinal Superficial Dorsal Horn.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- mGluR1 signaling is necessary for strengthening winner climbing fiber inputs in the developing mouse cerebellum.Proceedings of the National Academy of Sciences of the United States of America · 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
- Integrating endocannabinoid signaling, CCK interneurons, and hippocampal circuit dynamics in behaving animals.Neuron · 2025Review
- From Classical to Alternative Pathways of 2-Arachidonoylglycerol Synthesis: AlterAGs at the Crossroad of Endocannabinoid and Lysophospholipid Signaling.Molecules (Basel, Switzerland) · 2024Review
- AstrocyticCannabis and cannabinoid research · 2024Article
- Loss of synaptopodin impairs mGluR5 and protein synthesis-dependent mGluR-LTD at CA3-CA1 synapses.PNAS nexus · 2024Article
- Mechanisms of cannabinoid tolerance.Biochemical pharmacology · 2023Review
- 2-AG-Mediated Control of GABAergic Signaling Is Impaired in a Model of Epilepsy.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Mechanisms of endocannabinoid transport in the brain.British journal of pharmacology · 2022Review
- 2-Arachidonoylglycerol mobilization following brief synaptic stimulation in the dorsal lateral striatum requires glutamatergic and cholinergic neurotransmission.Neuropharmacology · 2022Article
- Phospholipase Cγ2 regulates endocannabinoid and eicosanoid networks in innate immune cells.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- mGluR5-Mediated eCB Signaling in the Nucleus Accumbens Controls Vulnerability to Depressive-Like Behaviors and Pain After Chronic Social Defeat Stress.Molecular neurobiology · 2021Article
- Combining electrophysiology and optogenetics for functional screening of pyramidal neurons in the mouse prefrontal cortex.STAR protocols · 2021Article
- Endocannabinoid-Mediated Control of Neural Circuit Excitability and Epileptic Seizures.Frontiers in neural circuits · 2021Review
- Tonic Endocannabinoid Signaling Gates Synaptic Plasticity in Dorsal Raphe Nucleus Serotonin Neurons Through Peroxisome Proliferator-Activated Receptors.Frontiers in pharmacology · 2021Article
- Activation of the mGluMolecular psychiatry · 2020Article
- Autism spectrum disorder-like behavior caused by reduced excitatory synaptic transmission in pyramidal neurons of mouse prefrontal cortex.Nature communications · 2020Article
67 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Endocannabinoids mediate retrograde signaling and modulate synaptic transmission in various regions of the CNS. Depolarization-induced elevation of intracellular Ca2+ concentration causes endocannabinoid-mediated suppression of excitatory/inhibitory synaptic transmission. Activation of G(q/11)-coupled receptors including group I metabotropic glutamate receptors (mGluRs) also causes endocannabinoid-mediated suppression of synaptic transmission. However, precise mechanisms of endocannabinoid production initiated by physiologically relevant synaptic activity remain to be determined. To address this problem, we made whole-cell recordings from Purkinje cells (PCs) in mouse cerebellar slices and examined their excitatory synapses arising from climbing fibers (CFs) and parallel fibers (PFs). We first characterized three distinct modes to induce endocannabinoid release by analyzing CF to PC synapses. The first mode is strong activation of mGluR subtype 1 (mGluR1)-phospholipase C (PLC) beta4 cascade without detectable Ca2+ elevation. The second mode is Ca2+ elevation to a micromolar range without activation of the mGluR1-PLCbeta4 cascade. The third mode is the Ca2+-assisted mGluR1-PLCbeta4 cascade that requires weak mGluR1 activation and Ca2+ elevation to a submicromolar range. By analyzing PF to PC synapses, we show that the third mode is essential for effective endocannabinoid release from PCs by excitatory synaptic activity. Furthermore, our biochemical analysis demonstrates that combined weak mGluR1 activation and mild depolarization in PCs effectively produces 2-arachidonoylglycerol (2-AG), a candidate of endocannabinoid, whereas either stimulus alone did not produce detectable 2-AG. Our results strongly suggest that under physiological conditions, excitatory synaptic inputs to PCs activate the Ca2+-assisted mGluR1-PLCbeta4 cascade, and thereby produce 2-AG, which retrogradely modulates synaptic transmission to PCs.
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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.