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. 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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Cell Reports
Department of Neuroscience

Sun, H, Takesian, A.E. (Anne E.), Wang, T.T. (Ting Ting), Lippman-Bell, J.J. (Jocelyn J.), Hensch, T.K. (Takao K.), & Jensen, F.E. (Frances E.). (2018). Early Seizures Prematurely Unsilence Auditory Synapses to Disrupt Thalamocortical Critical Period Plasticity. Cell Reports. doi:10.1016/j.celrep.2018.04.108