Lack of kainic acid-induced gamma oscillations predicts subsequent CA1 excitotoxic cell death
Gamma oscillations are a prominent feature of hippocampal network activity, but their functional role remains debated, ranging from mere epiphenomena to being crucial for information processing. Similarly, persistent gamma oscillations sometimes appear prior to epileptic discharges in patients with...
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| Format: | Article |
| Language: | en_US |
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Wiley Blackwell (Blackwell Publishing)
2012
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| Online Access: | http://hdl.handle.net/1721.1/70465 https://orcid.org/0000-0003-2839-8228 https://orcid.org/0000-0001-7149-3584 |
| _version_ | 1811078462252777472 |
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| author | Jinde, Seiichiro Belforte, Juan E. Yamamoto, Jun Wilson, Matthew A. Tonegawa, Susumu Nakazawa, Kazu |
| author2 | move to dc.description.sponsorship |
| author_facet | move to dc.description.sponsorship Jinde, Seiichiro Belforte, Juan E. Yamamoto, Jun Wilson, Matthew A. Tonegawa, Susumu Nakazawa, Kazu |
| author_sort | Jinde, Seiichiro |
| collection | MIT |
| description | Gamma oscillations are a prominent feature of hippocampal network activity, but their functional role remains debated, ranging from mere epiphenomena to being crucial for information processing. Similarly, persistent gamma oscillations sometimes appear prior to epileptic discharges in patients with mesial temporal sclerosis. However, the significance of this activity in hippocampal excitotoxicity is unclear. We assessed the relationship between kainic acid (KA)-induced gamma oscillations and excitotoxicity in genetically engineered mice in which N-methyl-d-aspartic acid receptor deletion was confined to CA3 pyramidal cells. Mutants showed reduced CA3 pyramidal cell firing and augmented sharp wave–ripple activity, resulting in higher susceptibility to KA-induced seizures, and leading to strikingly selective neurodegeneration in the CA1 subfield. Interestingly, the increase in KA-induced γ-aminobutyric acid (GABA) levels, and the persistent 30–50-Hz gamma oscillations, both of which were observed in control mice prior to the first seizure discharge, were abolished in the mutants. Consequently, on subsequent days, mutants manifested prolonged epileptiform activity and massive neurodegeneration of CA1 cells, including local GABAergic neurons. Remarkably, pretreatment with the potassium channel blocker α-dendrotoxin increased GABA levels, restored gamma oscillations, and prevented CA1 degeneration in the mutants. These results demonstrate that the emergence of low-frequency gamma oscillations predicts increased resistance to KA-induced excitotoxicity, raising the possibility that gamma oscillations may have potential prognostic value in the treatment of epilepsy. |
| first_indexed | 2024-09-23T11:00:11Z |
| format | Article |
| id | mit-1721.1/70465 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:00:11Z |
| publishDate | 2012 |
| publisher | Wiley Blackwell (Blackwell Publishing) |
| record_format | dspace |
| spelling | mit-1721.1/704652022-09-27T16:25:23Z Lack of kainic acid-induced gamma oscillations predicts subsequent CA1 excitotoxic cell death Jinde, Seiichiro Belforte, Juan E. Yamamoto, Jun Wilson, Matthew A. Tonegawa, Susumu Nakazawa, Kazu move to dc.description.sponsorship Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Picower Institute for Learning and Memory Wilson, Matthew A. Yamamoto, Jun Wilson, Matthew A. Tonegawa, Susumu Gamma oscillations are a prominent feature of hippocampal network activity, but their functional role remains debated, ranging from mere epiphenomena to being crucial for information processing. Similarly, persistent gamma oscillations sometimes appear prior to epileptic discharges in patients with mesial temporal sclerosis. However, the significance of this activity in hippocampal excitotoxicity is unclear. We assessed the relationship between kainic acid (KA)-induced gamma oscillations and excitotoxicity in genetically engineered mice in which N-methyl-d-aspartic acid receptor deletion was confined to CA3 pyramidal cells. Mutants showed reduced CA3 pyramidal cell firing and augmented sharp wave–ripple activity, resulting in higher susceptibility to KA-induced seizures, and leading to strikingly selective neurodegeneration in the CA1 subfield. Interestingly, the increase in KA-induced γ-aminobutyric acid (GABA) levels, and the persistent 30–50-Hz gamma oscillations, both of which were observed in control mice prior to the first seizure discharge, were abolished in the mutants. Consequently, on subsequent days, mutants manifested prolonged epileptiform activity and massive neurodegeneration of CA1 cells, including local GABAergic neurons. Remarkably, pretreatment with the potassium channel blocker α-dendrotoxin increased GABA levels, restored gamma oscillations, and prevented CA1 degeneration in the mutants. These results demonstrate that the emergence of low-frequency gamma oscillations predicts increased resistance to KA-induced excitotoxicity, raising the possibility that gamma oscillations may have potential prognostic value in the treatment of epilepsy. National Institutes of Health (U.S.). Intramural Research Program National Institutes of Health (U.S.) (Grant R01-MH078821) Japan Society for the Promotion of Science 2012-04-27T20:02:05Z 2012-04-27T20:02:05Z 2009-09 2009-06 Article http://purl.org/eprint/type/JournalArticle 0953-816X 1460-9568 http://hdl.handle.net/1721.1/70465 Jinde, Seiichiro et al. “Lack of Kainic Acid-induced Gamma Oscillations Predicts Subsequent CA1 Excitotoxic Cell Death.” European Journal of Neuroscience 30.6 (2009): 1036–1055. Web. 27 Apr. 2012. https://orcid.org/0000-0003-2839-8228 https://orcid.org/0000-0001-7149-3584 en_US http://dx.doi.org/10.1111/j.1460-9568.2009.06896.x European Journal of Neuroscience Creative Commons Attribution-Noncommercial-Share Alike 3.0 http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf Wiley Blackwell (Blackwell Publishing) PubMed Central |
| spellingShingle | Jinde, Seiichiro Belforte, Juan E. Yamamoto, Jun Wilson, Matthew A. Tonegawa, Susumu Nakazawa, Kazu Lack of kainic acid-induced gamma oscillations predicts subsequent CA1 excitotoxic cell death |
| title | Lack of kainic acid-induced gamma oscillations predicts subsequent CA1 excitotoxic cell death |
| title_full | Lack of kainic acid-induced gamma oscillations predicts subsequent CA1 excitotoxic cell death |
| title_fullStr | Lack of kainic acid-induced gamma oscillations predicts subsequent CA1 excitotoxic cell death |
| title_full_unstemmed | Lack of kainic acid-induced gamma oscillations predicts subsequent CA1 excitotoxic cell death |
| title_short | Lack of kainic acid-induced gamma oscillations predicts subsequent CA1 excitotoxic cell death |
| title_sort | lack of kainic acid induced gamma oscillations predicts subsequent ca1 excitotoxic cell death |
| url | http://hdl.handle.net/1721.1/70465 https://orcid.org/0000-0003-2839-8228 https://orcid.org/0000-0001-7149-3584 |
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