ArticlePLoS biology2015
Membrane-derived phospholipids control synaptic neurotransmission and plasticity.
Article in PLoS biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 80 citations in OpenAlex.
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- The Calcium-Binding Protein S100A10 (p11) Is Required for Normal Motor Performance by Regulating Vesicle Dynamics at Excitatory Synapses.Acta physiologica (Oxford, England) · 2026Article
- Plasma Phospholipid Biomarkers Related to the Risk of Cognitive Decline in the Elderly: Results from a Cohort Study.Nutrients · 2026Article
- Decoding lysophosphatidic acid signaling in physiology and disease: mapping the multimodal and multinodal signaling networks.Signal transduction and targeted therapy · 2025Review
- Lysophosphatidic acid selectively modulates excitatory transmission in hippocampal neurons.Cell & bioscience · 2025Article
- From Classical to Alternative Pathways of 2-Arachidonoylglycerol Synthesis: AlterAGs at the Crossroad of Endocannabinoid and Lysophospholipid Signaling.Molecules (Basel, Switzerland) · 2024Review
- Metabolomic and Proteomic Analysis of ApoE4-Carrying H4 Neuroglioma Cells in Alzheimer's Disease Using OrbiSIMS and LC-MS/MS.Analytical chemistry · 2024Article
- Effects of autotaxin and lysophosphatidic acid deficiencies on depression-like behaviors in mice exposed to chronic unpredictable mild stress.Neurobiology of stress · 2024Article
- Phospholipase Modulation of Synaptic Membrane Landscape: Driving Force Behind Memory Formation?Cold Spring Harbor perspectives in biology · 2024Review
- LPA1 receptors in the lateral habenula regulate negative affective states associated with alcohol withdrawal.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- Adipose tissue coregulates cognitive function.Science advances · 2023Article
- Shared biological mechanisms of depression and obesity: focus on adipokines and lipokines.Aging · 2023Review
- Inhibition of lysophosphatidic acid receptor 1 relieves PMN recruitment in CNS via LPA1/TSP1/CXCR2 pathway and alleviates disruption on blood-brain barrier following intracerebral haemorrhage in mice.Fluids and barriers of the CNS · 2023Article
- Cannabidiol modulates excitatory-inhibitory ratio to counter hippocampal hyperactivity.Neuron · 2023Article
- Lipids and Secretory Vesicle Exocytosis.Advances in neurobiology · 2023Article
- The Impact of Nicotine along with Oral Contraceptive Exposure on Brain Fatty Acid Metabolism in Female Rats.International journal of molecular sciences · 2022Article
- α-Glyceryl-phosphoryl-ethanolamine protects human hippocampal neurons from ageing-induced cellular alterations.The European journal of neuroscience · 2022Article
- Effects of Dietary n-3 LCPUFA Supplementation on the Hippocampus of Aging Female Mice: Impact on Memory, Lipid Raft-Associated Glutamatergic Receptors and Neuroinflammation.International journal of molecular sciences · 2022Article
- Targeting autotaxin impacts disease advance in the SOD1-G93A mouse model of amyotrophic lateral sclerosis.Brain pathology (Zurich, Switzerland) · 2022Article
- Positive association between plasmatic levels of orexin A and the endocannabinoid-derived 2-arachidonoyl lysophosphatidic acid in Alzheimer's disease.Frontiers in aging neuroscience · 2022Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Synaptic communication is a dynamic process that is key to the regulation of neuronal excitability and information processing in the brain. To date, however, the molecular signals controlling synaptic dynamics have been poorly understood. Membrane-derived bioactive phospholipids are potential candidates to control short-term tuning of synaptic signaling, a plastic event essential for information processing at both the cellular and neuronal network levels in the brain. Here, we showed that phospholipids affect excitatory and inhibitory neurotransmission by different degrees, loci, and mechanisms of action. Signaling triggered by lysophosphatidic acid (LPA) evoked rapid and reversible depression of excitatory and inhibitory postsynaptic currents. At excitatory synapses, LPA-induced depression depended on LPA1/Gαi/o-protein/phospholipase C/myosin light chain kinase cascade at the presynaptic site. LPA increased myosin light chain phosphorylation, which is known to trigger actomyosin contraction, and reduced the number of synaptic vesicles docked to active zones in excitatory boutons. At inhibitory synapses, postsynaptic LPA signaling led to dephosphorylation, and internalization of the GABAAγ2 subunit through the LPA1/Gα12/13-protein/RhoA/Rho kinase/calcineurin pathway. However, LPA-induced depression of GABAergic transmission was correlated with an endocytosis-independent reduction of GABAA receptors, possibly by GABAAγ2 dephosphorylation and subsequent increased lateral diffusion. Furthermore, endogenous LPA signaling, mainly via LPA1, mediated activity-dependent inhibitory depression in a model of experimental synaptic plasticity. Finally, LPA signaling, most likely restraining the excitatory drive incoming to motoneurons, regulated performance of motor output commands, a basic brain processing task. We propose that lysophospholipids serve as potential local messengers that tune synaptic strength to precedent activity of the neuron.
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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.