title: Epileptic synapsin triple knockout mice exhibit progressive long-term aberrant plasticity in the entorhinal cortex.
abstract: Studying epileptogenesis in a genetic model can facilitate the identification of factors that promote the conversion of a normal brain into one chronically prone to seizures. Synapsin triple-knockout (TKO) mice exhibit adult-onset epilepsy, thus allowing the characterization of events as preceding or following seizure onset. Although it has been proposed that a congenital reduction in inhibitory transmission is the underlying cause for epilepsy in these mice, young TKO mice are asymptomatic. We report that the genetic lesion exerts long-term progressive effects that extend well into adulthood. Although inhibitory transmission is initially reduced, it is subsequently strengthened relative to its magnitude in control mice, so that the excitation to inhibition balance in adult TKOs is inverted in favor of inhibition. In parallel, we observed long-term alterations in synaptic depression kinetics of excitatory transmission and in the extent of tonic inhibition, illustrating adaptations in synaptic properties. Moreover, age-dependent acceleration of the action potential did not occur in TKO cortical pyramidal neurons, suggesting wide-ranging secondary changes in brain excitability. In conclusion, although congenital impairments in inhibitory transmission may initiate epileptogenesis in the synapsin TKO mice, we suggest that secondary adaptations are crucial for the establishment of this epileptic network.
authors.affiliation: Department of Physiology and Cell Biology, Faculty of Health Sciences and Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
authors.forename: Maya
authors.initials: M
authors.lastname: Ketzef
authors.forename: Daniel
authors.initials: D
authors.lastname: Gitler
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D001927:Brain Diseases / Q000235:genetics* / Q000473:pathology*; D004558:Electric Stimulation; D018728:Entorhinal Cortex / Q000187:drug effects / Q000473:pathology*; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D018682:GABA Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000187:drug effects / Q000235:genetics*; D018408:Patch-Clamp Techniques; D012333:RNA, Messenger / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology; D016704:Synapsins / Q000172:deficiency*; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: C499978:Chrna5 protein, rat; D018683:Excitatory Amino Acid Agents; D018682:GABA Agents; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D026941:Sodium Channel Blockers; D016704:Synapsins; D013779:Tetrodotoxin