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Article Dans Une Revue Scientific Reports Année : 2016

LGI1 acts presynaptically to regulate excitatory synaptic transmission during early postnatal development

Résumé

The secreted leucine-rich glioma inactivated 1 (LGI1) protein is an important actor for human seizures of both genetic and autoimmune etiology: mutations in LGI1 cause inherited temporal lobe epilepsy, while LGI1 is involved in antibody-mediated encephalitis. Remarkably, Lgi1-deficient (Lgi1 −/−) mice recapitulate the epileptic disorder and display early-onset spontaneous seizures. To understand how Lgi1-deficiency leads to seizures during postnatal development, we here investigated the early functional and structural defects occurring before seizure onset in Lgi1 −/− mice. We found an increased excitatory synaptic transmission in hippocampal slices from Lgi1 −/− mice. No structural alteration in the morphology of pyramidal cell dendrites and synapses was observed at this stage, indicating that Lgi1-deficiency is unlikely to trigger early developmental abnormalities. Consistent with the presynaptic subcellular localization of the protein, Lgi1-deficiency caused presynaptic defects, with no alteration in postsynaptic AMPA receptor activity in Lgi1 −/− pyramidal cells before seizure onset. Presynaptic dysfunction led to increased synaptic glutamate levels, which were associated with hyperexcitable neuronal networks. Altogether, these data show that Lgi1 acts presynaptically as a negative modulator of excitatory synaptic transmission during early postnatal development. We therefore here reveal that increased presynaptic glutamate release is a key early event resulting from Lgi1-deficiency, which likely contributes to epileptogenesis.
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hal-01278922 , version 1 (25-02-2016)

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Morgane Boillot, Chun-Yao Lee, Camille Allene, Eric Leguern, Stéphanie Baulac, et al.. LGI1 acts presynaptically to regulate excitatory synaptic transmission during early postnatal development. Scientific Reports, 2016, 6, pp.21769. ⟨10.1038/srep21769⟩. ⟨hal-01278922⟩
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