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.

Additional Metadata
Keywords AMPA receptor, auditory cortex, autism, development, epilepsy, NBQX, neurodevelopmental disorders, NMDA receptor, silent synapses, tonotopic plasticity
Persistent URL dx.doi.org/10.1016/j.celrep.2018.04.108
Journal Cell Reports
Citation
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