6533b82ffe1ef96bd12953c8
RESEARCH PRODUCT
Membrane-Derived Phospholipids Control Synaptic Neurotransmission and Plasticity
Fernando MonteroLaura Gómez-pérezGermán Domínguez-víasMaría Jesús Medialdea-wandossellDavid González-foreroGuillermo Rodríguez-beyJosé Manuel García-verdugoBernardo Moreno-lópezVictoria García-moralessubject
MalePatch-Clamp TechniquesQH301-705.5NeurotransmissionBiologyInhibitory postsynaptic potentialSynaptic TransmissionGeneral Biochemistry Genetics and Molecular BiologyMicePregnancySynaptic augmentationMetaplasticityAnimalsRats WistarBiology (General)Motor Neuronsrho-Associated KinasesNeuronal PlasticityGeneral Immunology and MicrobiologyCalcineurinGeneral NeuroscienceReceptors GABA-ACell biologySynaptic fatigueBiochemistrySynapsesSynaptic plasticityExcitatory postsynaptic potentialFemalelipids (amino acids peptides and proteins)Synaptic signalingLysophospholipidsrhoA GTP-Binding ProteinGeneral Agricultural and Biological SciencesResearch Articledescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2015-05-01 |