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Article Dans Une Revue Journal of Neuroscience Année : 2023

Rescue of Normal Excitability in LGI1-Deficient Epileptic Neurons

Résumé

Leucine-rich glioma inactivated 1 (LGI1) is a glycoprotein secreted by neurons, the deletion of which leads to autosomal dominant lateral temporal lobe epilepsy. We previously showed that LGI1 deficiency in a mouse model (i.e., knock-out for LGI1 or KO-Lgi1) decreased Kv1.1 channel density at the axon initial segment (AIS) and at presynaptic terminals, thus enhancing both intrinsic excitability and glutamate release. However, it is not known whether normal excitability can be restored in epileptic neurons. Here, we show that the selective expression of LGI1 in KO-Lgi1 neurons from mice of both sexes, using single-cell electroporation, reduces intrinsic excitability and restores both the Kv1.1-mediated D-type current and Kv1.1 channels at the AIS. In addition, we show that the homeostatic-like shortening of the AIS length observed in KO-Lgi1 neurons is prevented in neurons electroporated with the Lgi1 gene. Furthermore, we reveal a spatial gradient of intrinsic excitability that is centered on the electroporated neuron. We conclude that expression of LGI1 restores normal excitability through functional Kv1 channels at the AIS.
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hal-04427386 , version 1 (30-01-2024)

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Johanna Extrémet, Jorge Ramirez-Franco, Laure Fronzaroli-Molinieres, Norah Boumedine-Guignon, Norbert Ankri, et al.. Rescue of Normal Excitability in LGI1-Deficient Epileptic Neurons. Journal of Neuroscience, 2023, 43 (50), pp.8596-8606. ⟨10.1523/jneurosci.0701-23.2023⟩. ⟨hal-04427386⟩
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