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

Publication date: 29 May 2018
Source:Cell Reports, Volume 23, Issue 9
Author(s): Hongyu Sun, Anne E. Takesian, Ting Ting Wang, Jocelyn J. Lippman-Bell, Takao K. Hensch, Frances E. Jensen
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.

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Teaser

Early-life seizures are often associated with intellectual disability and/or autism. Sun et al. show that seizures prematurely unsilence synapses to disrupt tonotopic plasticity in auditory cortex, revealing a mechanism for the relationship between seizures and later cognitive impairment.


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