Epileptic synapsin triple knockout mice exhibit progressive long-term aberrant plasticity in the entorhinal cortex

Maya Ketzef, Daniel Gitler

Research output: Contribution to journalArticlepeer-review

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.

Original languageAmerican English
Pages (from-to)996-1008
Number of pages13
JournalCerebral Cortex
Volume24
Issue number4
DOIs
StatePublished - 1 Jan 2014

Keywords

  • entorhinal cortex
  • epilepsy
  • inhibition
  • synapsin
  • synaptic transmission

All Science Journal Classification (ASJC) codes

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

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