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

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

Author information

1
Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Neuroscience, Carleton University, Ottawa, ON K1S 5B6, Canada.
2
F.M. Kirby Neurobiology Center, Department of Neurology, Boston Children's Hospital, Harvard Medical School, 300 Longwood Ave., Boston, MA 02115, USA.
3
Department of Neuroscience, Carleton University, Ottawa, ON K1S 5B6, Canada.
4
Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
5
F.M. Kirby Neurobiology Center, Department of Neurology, Boston Children's Hospital, Harvard Medical School, 300 Longwood Ave., Boston, MA 02115, USA; Center for Brain Science, Department of Molecular & Cellular Biology, Harvard University, 52 Oxford St., Cambridge, MA 02138, USA. Electronic address: hensch@mcb.harvard.edu.
6
Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: frances.jensen@uphs.upenn.edu.

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

PMID:
29847785
PMCID:
PMC6446922
DOI:
10.1016/j.celrep.2018.04.108
[Indexed for MEDLINE]
Free PMC Article

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