Enhanced long term potentiation and decreased AMPA receptor desensitization in the acute period following a single kainate induced early life seizure
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 sou...
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| Format: | Article |
| Language: | English |
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Elsevier
2016-03-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996115301091 |
| _version_ | 1818352333428359168 |
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| author | Heather O'Leary Paul B. Bernard Anna M. Castano Tim A. Benke |
| author_facet | Heather O'Leary Paul B. Bernard Anna M. Castano Tim A. Benke |
| author_sort | Heather O'Leary |
| collection | DOAJ |
| description | 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 ~50 days following kainic acid (KA) induced early life seizure (KA-ELS) in post-natal (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 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. |
| first_indexed | 2024-12-13T18:51:58Z |
| format | Article |
| id | doaj.art-3b6f12906b4640fe88ac995b4717a720 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-13T18:51:58Z |
| publishDate | 2016-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-3b6f12906b4640fe88ac995b4717a7202022-12-21T23:34:55ZengElsevierNeurobiology of Disease1095-953X2016-03-0187134144Enhanced long term potentiation and decreased AMPA receptor desensitization in the acute period following a single kainate induced early life seizureHeather O'Leary0Paul B. Bernard1Anna M. Castano2Tim A. Benke3Department of Pediatrics, University of Colorado, School of Medicine, 80045, USADepartment of Pediatrics, University of Colorado, School of Medicine, 80045, USADepartment of Pediatrics, University of Colorado, School of Medicine, 80045, USADepartment 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; Corresponding author at: Department of Pediatrics, University of Colorado Denver, School of Medicine, 12800 E 19th Ave, MS 8102, Aurora, CO 80045, USA.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 ~50 days following kainic acid (KA) induced early life seizure (KA-ELS) in post-natal (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 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.http://www.sciencedirect.com/science/article/pii/S0969996115301091Early life seizuresIntellectual disabilityAutismHippocampal dependent learningLong term potentiationAMPA receptors |
| spellingShingle | Heather O'Leary Paul B. Bernard Anna M. Castano Tim A. Benke Enhanced long term potentiation and decreased AMPA receptor desensitization in the acute period following a single kainate induced early life seizure Neurobiology of Disease Early life seizures Intellectual disability Autism Hippocampal dependent learning Long term potentiation AMPA receptors |
| title | Enhanced long term potentiation and decreased AMPA receptor desensitization in the acute period following a single kainate induced early life seizure |
| title_full | Enhanced long term potentiation and decreased AMPA receptor desensitization in the acute period following a single kainate induced early life seizure |
| title_fullStr | Enhanced long term potentiation and decreased AMPA receptor desensitization in the acute period following a single kainate induced early life seizure |
| title_full_unstemmed | Enhanced long term potentiation and decreased AMPA receptor desensitization in the acute period following a single kainate induced early life seizure |
| title_short | Enhanced long term potentiation and decreased AMPA receptor desensitization in the acute period following a single kainate induced early life seizure |
| title_sort | enhanced long term potentiation and decreased ampa receptor desensitization in the acute period following a single kainate induced early life seizure |
| topic | Early life seizures Intellectual disability Autism Hippocampal dependent learning Long term potentiation AMPA receptors |
| url | http://www.sciencedirect.com/science/article/pii/S0969996115301091 |
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