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.
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Authors | Hongyu Sun, Anne E Takesian, Ting Ting Wang, Jocelyn J Lippman-Bell, Takao K Hensch, Frances E Jensen |
Journal | Cell reports
(Cell Rep)
Vol. 23
Issue 9
Pg. 2533-2540
(05 29 2018)
ISSN: 2211-1247 [Electronic] United States |
PMID | 29847785
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved. |
Chemical References |
- Quinoxalines
- Receptors, AMPA
- 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
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Topics |
- Animals
- Auditory Perception
(physiology)
- Cerebral Cortex
(physiopathology)
- Female
- Male
- Mice, Inbred C57BL
- Neuronal Plasticity
(physiology)
- Quinoxalines
(pharmacology)
- Receptors, AMPA
(antagonists & inhibitors, metabolism)
- Seizures
(physiopathology)
- Synapses
(physiology)
- Thalamus
(physiopathology)
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