Glutamate Receptor 1 Phosphorylation at Serine 831 and 845 Modulates Seizure Susceptibility and Hippocampal Hyperexcitability after Early Life Seizures

• DOI: 10.1523/jneurosci.6121-11.2012
• Publication Date: 2012-12-05T17:46:54Z
• Authors: Sanjay N. Rakhade; Erin F. Fitzgerald; Peter M. Klein; Chengwen Zhou; Hongyu Sun; Richard L. Huganir; Frances E. Jensen
• Keywords: Hypoxia

Neonatal seizures can lead to later life epilepsy and neurobehavioral deficits, there are no treatments prevent these sequelae. We showed previously that hypoxia-induced in a neonatal rat model induce rapid phosphorylation of serine-831 (S831) Serine 845 (S845) sites the AMPA receptor GluR1 subunit neuronal hyperexcitability epilepsy, suggesting seizure-induced posttranslational modifications may represent novel therapeutic target. To unambiguously assess contribution sites, we examined seizure susceptibility wild-type mice versus transgenic knock-in with deficits S831 S845 [GluR1 double-phosphomutant (GluR1 DPM) mice]. Phosphorylation was significantly increased hippocampus cortex after single episode pentyleneterazol-induced postnatal day 7 (P7) mouse pups have higher threshold longer latencies seizures. Like rat, hypoxic P9 C57BL/6N resulted transient increases were associated enhanced later-life kainic-acid-induced In contrast, attenuated DPM mice, supporting role for network excitability. Finally, human hippocampal samples from autopsy cases also an increase S845, validation this potential target tissue.