Early Seizures Prematurely Unsilence Auditory Synapses to Disrupt Thalamocortical Critical Period Plasticity

Cell Rep. 2018 May 29;23(9):2533-2540. doi: 10.1016/j.celrep.2018.04.108.

Abstract

Heightened neural excitability in infancy and childhood results in increased susceptibility to seizures. Such early-life seizures are associated with language deficits and autism that can result from aberrant development of the auditory cortex. Here, we show that early-life seizures disrupt a critical period (CP) for tonotopic map plasticity in primary auditory cortex (A1). We show that this CP is characterized by a prevalence of "silent," NMDA-receptor (NMDAR)-only, glutamate receptor synapses in auditory cortex that become "unsilenced" due to activity-dependent AMPA receptor (AMPAR) insertion. Induction of seizures prior to this CP occludes tonotopic map plasticity by prematurely unsilencing NMDAR-only synapses. Further, brief treatment with the AMPAR antagonist NBQX following seizures, prior to the CP, prevents synapse unsilencing and permits subsequent A1 plasticity. These findings reveal that early-life seizures modify CP regulators and suggest that therapeutic targets for early post-seizure treatment can rescue CP plasticity.

Keywords: AMPA receptor; NBQX; NMDA receptor; auditory cortex; autism; development; epilepsy; neurodevelopmental disorders; silent synapses; tonotopic plasticity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Auditory Perception / physiology*
  • Cerebral Cortex / physiopathology*
  • Female
  • Male
  • Mice, Inbred C57BL
  • Neuronal Plasticity / physiology*
  • Quinoxalines / pharmacology
  • Receptors, AMPA / antagonists & inhibitors
  • Receptors, AMPA / metabolism
  • Seizures / physiopathology*
  • Synapses / physiology*
  • Thalamus / physiopathology*

Substances

  • Quinoxalines
  • Receptors, AMPA
  • 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline