title: Enhanced long term potentiation and decreased AMPA receptor desensitization in the acute period following a single kainate induced early life seizure.
abstract: 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 CA1 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 ~50days following kainic acid (KA) induced early life seizure (KA-ELS) in post-natal (P) 7day 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 7days, post KA-ELS. Our results show for the first time enhanced LTP 7days after KA-ELS, but no change 2days post KA-ELS. Additionally, we report that ionotropic α-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.
authors.affiliation: Department of Pediatrics, University of Colorado, School of Medicine, 80045, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: O'Leary
authors.affiliation: Department of Pediatrics, University of Colorado, School of Medicine, 80045, USA.
authors.forename: Paul B
authors.initials: PB
authors.lastname: Bernard
authors.affiliation: Department of Pediatrics, University of Colorado, School of Medicine, 80045, USA.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Castano
authors.affiliation: Department of Pediatrics, University of Colorado, School of Medicine, 80045, USA; Department of Neurology, University of Colorado, School of Medicine, 80045, USA; Department of Pharmacology, University of Colorado, School of Medicine, 80045, USA; Department of Otolaryngology, University of Colorado, School of Medicine, 80045, USA; Neuroscience Graduate Program, University of Colorado, School of Medicine, 80045, USA. Electronic address: Tim.Benke@ucdenver.edu.
authors.forename: Tim A
authors.initials: TA
authors.lastname: Benke
mesh_terms: D000208:Acute Disease; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D056547:CA1 Region, Hippocampal / Q000503:physiopathology*; D004195:Disease Models, Animal; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D007608:Kainic Acid; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D018408:Patch-Clamp Techniques; D010766:Phosphorylation / Q000502:physiology; D017966:Pyramidal Cells / Q000502:physiology; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012640:Seizures / Q000503:physiopathology*; D013995:Time; D046509:Tissue Culture Techniques
chemical_list: D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D007608:Kainic Acid
keywords: AMPA receptors; Autism; Early life seizures; Hippocampal dependent learning; Intellectual disability; Long term potentiation; NMDA receptors