Enhanced long term potentiation and decreased AMPA receptor desensitization in the acute period following a single kainate induced early life seizure

NEUROBIOLOGY OF DISEASE

卷:87

Article

O'Leary, Heather¹  Bernard, Paul B.¹  Castano, Anna M.¹  Benke, Tim A.^1,2,3,4,5 

[1] Univ Colorado, Sch Med, Dept Pediat, Aurora, CO 80045 USA

[2] Univ Colorado, Sch Med, Dept Neurol, Aurora, CO 80045 USA

[3] Univ Colorado, Sch Med, Dept Pharmacol, Aurora, CO 80045 USA

[4] Univ Colorado, Sch Med, Dept Otolaryngol, Aurora, CO 80045 USA

[5] Univ Colorado, Sch Med, Neurosci Grad Program, Aurora, CO 80045 USA

关键词: Early life seizures;    Intellectual disability;    Autism;    Hippocampal dependent learning;    Long term potentiation;    AMPA receptors;    NMDA receptors;   

DOI  :  10.1016/j.nbd.2015.12.005

来源: Elsevier

【 摘 要 】

Neonatal seizures are associated with long term disabilities including epilepsy and cognitive deficits. Using a neonatal seizure rat model that does not develop epilepsy, but develops a phenotype consistent with other models of intellectual disability (ID) and autism spectrum disorders (ASD), we sought to isolate the acute effects of a single episode of early life seizure on hippocampal CM synaptic development and plasticity. We have previously shown chronic changes in glutamatergic synapses, loss of long term potentiation (LTP) and enhanced long term depression (LTD), in the adult male rat similar to 50 days following kainic acid (KA) induced early life seizure (KA-ELS) in postnatal (P) 7 day old male Sprague-Dawley rats. In the present work, we examined the electrophysiological properties and expression levels of glutamate receptors in the acute period, 2 and 7 days, post KA-ELS. Our results show for the first time enhanced LTP 7 days after KA-ELS, but no change 2 days post KA-ELS. Additionally, we report that ionotropic alpha-amino-3-hydroxy-5-methyl-isoxazole-propionic acid type glutamate receptor (AMPAR) desensitization is decreased in the same time frame, with no changes in AMPAR expression, phosphorylation, or membrane insertion. Inappropriate enhancement of the synaptic connections in the acute period after the seizure could alter the normal patterning of synaptic development in the hippocampus during this critical period and contribute to learning deficits. Thus, this study demonstrates a novel mechanism by which KA-ELS alters early network properties that potentially lead to adverse outcomes. (C) 2015 Elsevier Inc. All rights reserved.

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