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Role of PRG-1 (plasticity related gene-1) in glutamatergic transmission

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Plasticity related gene-1 (PRG-1) is a brain-specific membrane protein related to lipid phosphate phosphatases, which acts in the hippocampus specifically at the excitatory synapse terminating on glutamatergic neurons. Deletion of prg-1 in mice leads to epileptic seizures and augmentation of EPS Cs, but not IPS Cs. In utero electroporation of PRG -1 into deficient animals revealed that PRG -1 modulates excitation at the synaptic junction. Mutation of the extracellular domain of PRG -1 crucial for its interaction with lysophosphatidic acid (LPA) abolished the ability to prevent hyperexcitability. As LPA application in vitro induced hyperexcitability in wild-type but not in LPA2 receptor-deficient animals, and uptake of phospholipids is reduced in PRG -1-deficient neurons, we assessed PRG -1/LPA2 receptor-deficient animals, and found that the pathophysiology observed in the PRG -1-deficient mice was fully reverted. Thus, we propose PRG -1 as an important player in the modulatory control of hippocampal excitability dependent on presynaptic LPA2 receptor signaling.

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