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

• Published in: Cell reports (Cambridge) Vol. 23; no. 9; pp. 2533 - 2540
• Main Authors: Sun, Hongyu, Takesian, Anne E., Wang, Ting Ting, Lippman-Bell, Jocelyn J., Hensch, Takao K., Jensen, Frances E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 29.05.2018; Elsevier
• Subjects: AMPA receptor; Animals; auditory cortex; Auditory Perception - physiology; autism; Cerebral Cortex - physiopathology; development; epilepsy; Female; Male; Mice, Inbred C57BL; NBQX; neurodevelopmental disorders; Neuronal Plasticity - physiology; NMDA receptor; Quinoxalines - pharmacology; Receptors, AMPA - antagonists & inhibitors; Receptors, AMPA - metabolism; Seizures - physiopathology; silent synapses; Synapses - physiology; Thalamus - physiopathology; tonotopic plasticity; epilepsy; development; AMPA receptor; auditory cortex; tonotopic plasticity; NMDA receptor; silent synapses; neurodevelopmental disorders; autism; NBQX
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2018.04.108

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. [Display omitted] •Early-life seizures disrupt a critical period for tonotopic map plasticity in A1•Maturational decrease in NMDA-only silent synapses characterizes this CP•Seizures accelerate synapse unsilencing by AMPA receptor insertion•An AMPAR antagonist prevents synapse unsilencing and rescues 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.