title: Epilepsy gene LGI1 regulates postnatal developmental remodeling of retinogeniculate synapses.
abstract: Retinogeniculate connections undergo postnatal refinement in the developing visual system. Here we report that non-ion channel epilepsy gene LGI1 (leucine-rich glioma-inactivated), mutated in human autosomal dominant lateral temporal lobe epilepsy (ADLTE), regulates postnatal pruning of retinal axons in visual relay thalamus. By introducing an ADLTE-associated truncated mutant LGI1 (836delC) or excess full-length LGI1 into transgenic mice, we found that mutant LGI1 blocks, whereas excess LGI1 accelerates, retinogeniculate axon pruning. The normal postnatal single fiber strengthening was arrested by mutant LGI1 and, contrastingly, was enhanced by excess wild-type LGI1. The maximum response of the retinogeniculate synapses, conversely, remained the same in mature LGI1 transgenic mice, indicating that mutant LGI1 blocks, whereas excess wild-type LGI1 promotes, weak axon fiber elimination. Heterozygous deletion of the LGI1 gene, as found in ADLTE patients, inhibited postnatal retinogeniculate synapse elimination, an effect similar to the ADLTE truncated mutant LGI1. The results identify sensory axon remodeling defects in a sensory aura-associated human epilepsy disorder.
authors.affiliation: Department of Neurology and Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Yu-Dong
authors.initials: YD
authors.lastname: Zhou
authors.forename: Dawei
authors.initials: D
authors.lastname: Zhang
authors.forename: Ekim
authors.initials: E
authors.lastname: Ozkaynak
authors.forename: Xuan
authors.initials: X
authors.lastname: Wang
authors.forename: Ekkehard M
authors.initials: EM
authors.lastname: Kasper
authors.forename: Eric
authors.initials: E
authors.lastname: Leguern
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Baulac
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Anderson
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D005829:Geniculate Bodies / Q000166:cytology* / Q000254:growth & development*; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000502:physiology*; D009900:Optic Nerve / Q000254:growth & development / Q000502:physiology; D018408:Patch-Clamp Techniques; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011930:Reaction Time / Q000235:genetics; D018091:Receptors, AMPA / Q000378:metabolism; D013569:Synapses / Q000235:genetics / Q000502:physiology*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C492120:Lgi1 protein, mouse; D011506:Proteins; D018091:Receptors, AMPA