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In vivo assessment of mechanisms underlying the neurovascular basis of postictal amnesia
Long-lasting confusion and memory difficulties during the postictal state remain a major unmet problem in epilepsy that lacks pathophysiological explanation and treatment. We previously identified that long-lasting periods of severe postictal hypoperfusion/hypoxia, not seizures per se, are associate...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490395/ https://www.ncbi.nlm.nih.gov/pubmed/32929133 http://dx.doi.org/10.1038/s41598-020-71935-6 |
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author | Farrell, Jordan S. Colangeli, Roberto Dudok, Barna Wolff, Marshal D. Nguyen, Sarah L. Jackson, Jesse Dickson, Clayton T. Soltesz, Ivan Teskey, G. Campbell |
author_facet | Farrell, Jordan S. Colangeli, Roberto Dudok, Barna Wolff, Marshal D. Nguyen, Sarah L. Jackson, Jesse Dickson, Clayton T. Soltesz, Ivan Teskey, G. Campbell |
author_sort | Farrell, Jordan S. |
collection | PubMed |
description | Long-lasting confusion and memory difficulties during the postictal state remain a major unmet problem in epilepsy that lacks pathophysiological explanation and treatment. We previously identified that long-lasting periods of severe postictal hypoperfusion/hypoxia, not seizures per se, are associated with memory impairment after temporal lobe seizures. While this observation suggests a key pathophysiological role for insufficient energy delivery, it is unclear how the networks that underlie episodic memory respond to vascular constraints that ultimately give rise to amnesia. Here, we focused on cellular/network level analyses in the CA1 of hippocampus in vivo to determine if neural activity, network oscillations, synaptic transmission, and/or synaptic plasticity are impaired following kindled seizures. Importantly, the induction of severe postictal hypoperfusion/hypoxia was prevented in animals treated by a COX-2 inhibitor, which experimentally separated seizures from their vascular consequences. We observed complete activation of CA1 pyramidal neurons during brief seizures, followed by a short period of reduced activity and flattening of the local field potential that resolved within minutes. During the postictal state, constituting tens of minutes to hours, we observed no changes in neural activity, network oscillations, and synaptic transmission. However, long-term potentiation of the temporoammonic pathway to CA1 was impaired in the postictal period, but only when severe local hypoxia occurred. Lastly, we tested the ability of rats to perform object-context discrimination, which has been proposed to require temporoammonic input to differentiate between sensory experience and the stored representation of the expected object-context pairing. Deficits in this task following seizures were reversed by COX-2 inhibition, which prevented severe postictal hypoxia. These results support a key role for hypoperfusion/hypoxia in postictal memory impairments and identify that many aspects of hippocampal network function are resilient during severe hypoxia except for long-term synaptic plasticity. |
format | Online Article Text |
id | pubmed-7490395 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-74903952020-09-16 In vivo assessment of mechanisms underlying the neurovascular basis of postictal amnesia Farrell, Jordan S. Colangeli, Roberto Dudok, Barna Wolff, Marshal D. Nguyen, Sarah L. Jackson, Jesse Dickson, Clayton T. Soltesz, Ivan Teskey, G. Campbell Sci Rep Article Long-lasting confusion and memory difficulties during the postictal state remain a major unmet problem in epilepsy that lacks pathophysiological explanation and treatment. We previously identified that long-lasting periods of severe postictal hypoperfusion/hypoxia, not seizures per se, are associated with memory impairment after temporal lobe seizures. While this observation suggests a key pathophysiological role for insufficient energy delivery, it is unclear how the networks that underlie episodic memory respond to vascular constraints that ultimately give rise to amnesia. Here, we focused on cellular/network level analyses in the CA1 of hippocampus in vivo to determine if neural activity, network oscillations, synaptic transmission, and/or synaptic plasticity are impaired following kindled seizures. Importantly, the induction of severe postictal hypoperfusion/hypoxia was prevented in animals treated by a COX-2 inhibitor, which experimentally separated seizures from their vascular consequences. We observed complete activation of CA1 pyramidal neurons during brief seizures, followed by a short period of reduced activity and flattening of the local field potential that resolved within minutes. During the postictal state, constituting tens of minutes to hours, we observed no changes in neural activity, network oscillations, and synaptic transmission. However, long-term potentiation of the temporoammonic pathway to CA1 was impaired in the postictal period, but only when severe local hypoxia occurred. Lastly, we tested the ability of rats to perform object-context discrimination, which has been proposed to require temporoammonic input to differentiate between sensory experience and the stored representation of the expected object-context pairing. Deficits in this task following seizures were reversed by COX-2 inhibition, which prevented severe postictal hypoxia. These results support a key role for hypoperfusion/hypoxia in postictal memory impairments and identify that many aspects of hippocampal network function are resilient during severe hypoxia except for long-term synaptic plasticity. Nature Publishing Group UK 2020-09-14 /pmc/articles/PMC7490395/ /pubmed/32929133 http://dx.doi.org/10.1038/s41598-020-71935-6 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Farrell, Jordan S. Colangeli, Roberto Dudok, Barna Wolff, Marshal D. Nguyen, Sarah L. Jackson, Jesse Dickson, Clayton T. Soltesz, Ivan Teskey, G. Campbell In vivo assessment of mechanisms underlying the neurovascular basis of postictal amnesia |
title | In vivo assessment of mechanisms underlying the neurovascular basis of postictal amnesia |
title_full | In vivo assessment of mechanisms underlying the neurovascular basis of postictal amnesia |
title_fullStr | In vivo assessment of mechanisms underlying the neurovascular basis of postictal amnesia |
title_full_unstemmed | In vivo assessment of mechanisms underlying the neurovascular basis of postictal amnesia |
title_short | In vivo assessment of mechanisms underlying the neurovascular basis of postictal amnesia |
title_sort | in vivo assessment of mechanisms underlying the neurovascular basis of postictal amnesia |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490395/ https://www.ncbi.nlm.nih.gov/pubmed/32929133 http://dx.doi.org/10.1038/s41598-020-71935-6 |
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