Membrane-Derived Phospholipids Control Synaptic Neurotransmission and Plasticity
| العنوان: | Membrane-Derived Phospholipids Control Synaptic Neurotransmission and Plasticity |
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| المؤلفون: | Fernando Montero, Laura Gómez-Pérez, Germán Domínguez-Vías, María Jesús Medialdea-Wandossell, David González-Forero, Guillermo Rodríguez-Bey, José Manuel García-Verdugo, Bernardo Moreno-López, Victoria García-Morales |
| المصدر: | PLOS BIOLOGY r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF) instname r-CIPF: Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF) Centro de Investigación Principe Felipe (CIPF) PLoS Biology, Vol 13, Iss 5, p e1002153 (2015) PLoS Biology |
| بيانات النشر: | PUBLIC LIBRARY SCIENCE, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Male, Patch-Clamp Techniques, QH301-705.5, Neurotransmission, Biology, Inhibitory postsynaptic potential, Synaptic Transmission, General Biochemistry, Genetics and Molecular Biology, Mice, Pregnancy, Synaptic augmentation, Metaplasticity, Animals, Rats, Wistar, Biology (General), Motor Neurons, rho-Associated Kinases, Neuronal Plasticity, General Immunology and Microbiology, Calcineurin, General Neuroscience, Receptors, GABA-A, Cell biology, Synaptic fatigue, Biochemistry, Synapses, Synaptic plasticity, Excitatory postsynaptic potential, Female, lipids (amino acids, peptides, and proteins), Synaptic signaling, Lysophospholipids, rhoA GTP-Binding Protein, General Agricultural and Biological Sciences, Research Article |
| الوصف: | 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. Lysophospholipids derived from membranes are important regulators of neurotransmission, acting as local messengers that couple synaptic strength to recent neuronal activity. Author Summary Neuronal networks are modules of synaptic connectivity that underlie all brain functions, from simple reflexes to complex cognitive processes. Synaptic plasticity allows these networks to adapt to changing external and internal environments. Membrane-derived bioactive phospholipids are potential candidates to control short-term synaptic plasticity. We demonstrate that lysophosphatidic acid (LPA), an important intermediary in lipid metabolism, depresses the main excitatory and inhibitory synaptic systems by different mechanisms. LPA depresses inhibitory synaptic transmission by reducing the number of postsynaptic receptors at inhibitory synapses; whereas it depresses excitatory synaptic transmission by decreasing the size of the ready-to-use synaptic vesicle pool at excitatory terminals. Finally, we demonstrate that LPA signaling contributes to the performance of motor output commands in adult animals. Our data documents that synaptic strength and neuronal activity are modulated by products of membrane phospholipid metabolism, which suggests that bioactive phospholipids are candidates in coupling brain function to the metabolic status of the organism. |
| تدمد: | 1545-7885 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fe66f4fb86c6bfd79ffdb8d7c1c83d3e https://fundanet.cipf.es/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=3320 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....fe66f4fb86c6bfd79ffdb8d7c1c83d3e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15457885 |
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