ArticleNature neuroscience2023
Postsynaptic synucleins mediate endocannabinoid signaling.
Article in Nature neuroscience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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Who cites it
26 citing papers in PubMed.
- A light-controlled tetanus neurotoxin enables rapid and reversible synaptic inhibition in vivo.Nature methods · 2026Article
- mGluR5 in ECAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Light-activated tetanus neurotoxin for conditional proteolysis and inducible synaptic inhibition in vivo.Nature methods · 2026Article
- Disruption of the LRRK2 substrate RAB12 facilitates neurotransmission and causes hyperactivity in mice.NPJ Parkinson's disease · 2026Article
- Cognitive and Motor Dysfunction in STXBP1 R406H Mice.Journal of molecular neuroscience : MN · 2026Article
- Multiple Roles of Cannabinoids in the Olfactory System.Brain sciences · 2026Review
- α-Synuclein expression is required for somatodendritic dopamine release and immediate early gene induction.Science advances · 2026Article
- Circuit mechanisms governing endocannabinoid modulation of affective behaviour and stress adaptation.Nature reviews. Neuroscience · 2025Review
- Refinement of efficient encodings of movement in the dorsolateral striatum throughout learning.Cell reports · 2025Article
- Cannabinoids in Chronic Pain: Clinical Outcomes, Adverse Effects and Legal Challenges.Neurology international · 2025Review
- Ppp2r1a haploinsufficiency increases excitatory synaptic transmission and decreases spatial learning by impairing endocannabinoid signaling.The Journal of clinical investigation · 2025Article
- Integrating endocannabinoid signaling, CCK interneurons, and hippocampal circuit dynamics in behaving animals.Neuron · 2025Review
- Article
- The role of dopaminergic medication and specific pathway alterations in idiopathic andScience advances · 2025Article
- Role of the Endocannabinoid System in Fibromyalgia.Current issues in molecular biology · 2025Review
- The endocannabinoid 2-arachidonoylglycerol is released and transported on demand via extracellular microvesicles.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Prasinezumab slows motor progression in Parkinsons disease: beyond the clinical data.NPJ Parkinson's disease · 2025Review
- Mechanisms of neuromodulatory volume transmission.Molecular psychiatry · 2024Review
- Current trends in basic research on Parkinson's disease: from mitochondria, lysosome to α-synuclein.Journal of neural transmission (Vienna, Austria : 1996) · 2024Review
- Retrograde endocannabinoid signaling at inhibitory synapses in vivo.Science (New York, N.Y.) · 2024Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Endocannabinoids are among the most powerful modulators of synaptic transmission throughout the nervous system, and yet little is understood about the release of endocannabinoids from postsynaptic compartments. Here we report an unexpected finding that endocannabinoid release requires synucleins, key contributors to Parkinson's disease. We show that endocannabinoids are released postsynaptically by a synuclein-dependent and SNARE-dependent mechanism. Specifically, we found that synuclein deletion blocks endocannabinoid-dependent synaptic plasticity; this block is reversed by postsynaptic expression of wild-type but not of mutant α-synuclein. Whole-cell recordings and direct optical monitoring of endocannabinoid signaling suggest that the synuclein deletion specifically blocks endocannabinoid release. Given the presynaptic role of synucleins in regulating vesicle lifecycle, we hypothesize that endocannabinoids are released via a membrane interaction mechanism. Consistent with this hypothesis, postsynaptic expression of tetanus toxin light chain, which cleaves synaptobrevin SNAREs, also blocks endocannabinoid-dependent signaling. The unexpected finding that endocannabinoids are released via a synuclein-dependent mechanism is consistent with a general function of synucleins in membrane trafficking and adds a piece to the longstanding puzzle of how neurons release endocannabinoids to induce synaptic plasticity.
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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 Socratic graph.