Termination of convulsion seizures by destabilizing and perturbing seizure memory engrams
Epileptogenesis, arising from alterations in synaptic strength, shares mechanistic and phenotypic parallels with memory formation. However, direct evidence supporting the existence of seizure memory remains scarce. Leveraging a conditioned seizure memory (CSM) paradigm, we found that CSM enabled the...
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| Veröffentlicht in: | Science advances 2024-03, Vol.10 (12), p.eadk9484-eadk9484 |
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| creator | Lai, Shirong Zhang, Libo Tu, Xinyu Ma, Xinyue Song, Yujing Cao, Kexin Li, Miaomiao Meng, Jihong Shi, Yiqiang Wu, Qing Yang, Chen Lan, Zifan Lau, Chunyue Geoffrey Shi, Jie Ma, Weining Li, Shaoyi Xue, Yan-Xue Huang, Zhuo |
| description | Epileptogenesis, arising from alterations in synaptic strength, shares mechanistic and phenotypic parallels with memory formation. However, direct evidence supporting the existence of seizure memory remains scarce. Leveraging a conditioned seizure memory (CSM) paradigm, we found that CSM enabled the environmental cue to trigger seizure repetitively, and activating cue-responding engram cells could generate CSM artificially. Moreover, cue exposure initiated an analogous process of memory reconsolidation driven by mammalian target of rapamycin-brain-derived neurotrophic factor signaling. Pharmacological targeting of the mammalian target of rapamycin pathway within a limited time window reduced seizures in animals and interictal epileptiform discharges in patients with refractory seizures. Our findings reveal a causal link between seizure memory engrams and seizures, which leads us to a deeper understanding of epileptogenesis and points to a promising direction for epilepsy treatment. |
| doi_str_mv | 10.1126/sciadv.adk9484 |
| format | Article |
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However, direct evidence supporting the existence of seizure memory remains scarce. Leveraging a conditioned seizure memory (CSM) paradigm, we found that CSM enabled the environmental cue to trigger seizure repetitively, and activating cue-responding engram cells could generate CSM artificially. Moreover, cue exposure initiated an analogous process of memory reconsolidation driven by mammalian target of rapamycin-brain-derived neurotrophic factor signaling. Pharmacological targeting of the mammalian target of rapamycin pathway within a limited time window reduced seizures in animals and interictal epileptiform discharges in patients with refractory seizures. Our findings reveal a causal link between seizure memory engrams and seizures, which leads us to a deeper understanding of epileptogenesis and points to a promising direction for epilepsy treatment.</description><identifier>ISSN: 2375-2548</identifier><identifier>EISSN: 2375-2548</identifier><identifier>DOI: 10.1126/sciadv.adk9484</identifier><identifier>PMID: 38507477</identifier><language>eng</language><publisher>United States: American Association for the Advancement of Science</publisher><subject>Animals ; Electroencephalography ; Epilepsy ; Humans ; Mammals ; Neuroscience ; SciAdv r-articles ; Seizures - etiology ; Sirolimus ; TOR Serine-Threonine Kinases</subject><ispartof>Science advances, 2024-03, Vol.10 (12), p.eadk9484-eadk9484</ispartof><rights>Copyright © 2024 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). 2024 The Authors</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c346t-6d37e92b5888ebe24f57bf461887f97239546e21c036aa74cdce9bf7adce4a303</cites><orcidid>0000-0001-9750-2514 ; 0000-0003-2979-0045 ; 0000-0003-0174-2842 ; 0000-0001-6114-1593 ; 0000-0003-0868-0912 ; 0009-0004-0976-8718 ; 0000-0003-0857-2428 ; 0009-0006-6203-366X ; 0000-0001-6567-8160 ; 0000-0001-7359-6835 ; 0009-0008-7615-0861 ; 0009-0006-9615-7468 ; 0000-0001-9198-4778 ; 0000-0002-6829-1452</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10954199/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10954199/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38507477$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lai, Shirong</creatorcontrib><creatorcontrib>Zhang, Libo</creatorcontrib><creatorcontrib>Tu, Xinyu</creatorcontrib><creatorcontrib>Ma, Xinyue</creatorcontrib><creatorcontrib>Song, Yujing</creatorcontrib><creatorcontrib>Cao, Kexin</creatorcontrib><creatorcontrib>Li, Miaomiao</creatorcontrib><creatorcontrib>Meng, Jihong</creatorcontrib><creatorcontrib>Shi, Yiqiang</creatorcontrib><creatorcontrib>Wu, Qing</creatorcontrib><creatorcontrib>Yang, Chen</creatorcontrib><creatorcontrib>Lan, Zifan</creatorcontrib><creatorcontrib>Lau, Chunyue Geoffrey</creatorcontrib><creatorcontrib>Shi, Jie</creatorcontrib><creatorcontrib>Ma, Weining</creatorcontrib><creatorcontrib>Li, Shaoyi</creatorcontrib><creatorcontrib>Xue, Yan-Xue</creatorcontrib><creatorcontrib>Huang, Zhuo</creatorcontrib><title>Termination of convulsion seizures by destabilizing and perturbing seizure memory engrams</title><title>Science advances</title><addtitle>Sci Adv</addtitle><description>Epileptogenesis, arising from alterations in synaptic strength, shares mechanistic and phenotypic parallels with memory formation. However, direct evidence supporting the existence of seizure memory remains scarce. Leveraging a conditioned seizure memory (CSM) paradigm, we found that CSM enabled the environmental cue to trigger seizure repetitively, and activating cue-responding engram cells could generate CSM artificially. Moreover, cue exposure initiated an analogous process of memory reconsolidation driven by mammalian target of rapamycin-brain-derived neurotrophic factor signaling. Pharmacological targeting of the mammalian target of rapamycin pathway within a limited time window reduced seizures in animals and interictal epileptiform discharges in patients with refractory seizures. Our findings reveal a causal link between seizure memory engrams and seizures, which leads us to a deeper understanding of epileptogenesis and points to a promising direction for epilepsy treatment.</description><subject>Animals</subject><subject>Electroencephalography</subject><subject>Epilepsy</subject><subject>Humans</subject><subject>Mammals</subject><subject>Neuroscience</subject><subject>SciAdv r-articles</subject><subject>Seizures - etiology</subject><subject>Sirolimus</subject><subject>TOR Serine-Threonine Kinases</subject><issn>2375-2548</issn><issn>2375-2548</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUT1PwzAQtRCIVqUrI8rI0uKv2PGEUMWXVImlDEyWk1yKIbGLnVRqfz2pWqoy3b27d-_u9BC6JnhKCBV3sbCmXE9N-a14xs_QkDKZTmjKs_OTfIDGMX5hjAkXIiXqEg1YlmLJpRyijwWExjrTWu8SXyWFd-uujjsUwW67ADHJN0kJsTW5re3WumViXJmsILRdyHfwQEwaaHzYJOCWwTTxCl1Upo4wPsQRen96XMxeJvO359fZw3xSMC7aiSiZBEXzNMsyyIHyKpV5xQXJMlkpSZlKuQBKCsyEMZIXZQEqr6TpIzcMsxG63-uuuryBvuraYGq9CrYxYaO9sfp_x9lPvfRrTXAvTZTqFW4PCsH_dP2nurGxgLo2DnwXNVWSESxoSnvqdE8tgo8xQHXcQ7DeeaL3nuiDJ_3Azel1R_qfA-wXwUiNRg</recordid><startdate>20240322</startdate><enddate>20240322</enddate><creator>Lai, Shirong</creator><creator>Zhang, Libo</creator><creator>Tu, Xinyu</creator><creator>Ma, Xinyue</creator><creator>Song, Yujing</creator><creator>Cao, Kexin</creator><creator>Li, Miaomiao</creator><creator>Meng, Jihong</creator><creator>Shi, Yiqiang</creator><creator>Wu, Qing</creator><creator>Yang, Chen</creator><creator>Lan, Zifan</creator><creator>Lau, Chunyue Geoffrey</creator><creator>Shi, Jie</creator><creator>Ma, Weining</creator><creator>Li, Shaoyi</creator><creator>Xue, Yan-Xue</creator><creator>Huang, Zhuo</creator><general>American Association for the Advancement of Science</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-9750-2514</orcidid><orcidid>https://orcid.org/0000-0003-2979-0045</orcidid><orcidid>https://orcid.org/0000-0003-0174-2842</orcidid><orcidid>https://orcid.org/0000-0001-6114-1593</orcidid><orcidid>https://orcid.org/0000-0003-0868-0912</orcidid><orcidid>https://orcid.org/0009-0004-0976-8718</orcidid><orcidid>https://orcid.org/0000-0003-0857-2428</orcidid><orcidid>https://orcid.org/0009-0006-6203-366X</orcidid><orcidid>https://orcid.org/0000-0001-6567-8160</orcidid><orcidid>https://orcid.org/0000-0001-7359-6835</orcidid><orcidid>https://orcid.org/0009-0008-7615-0861</orcidid><orcidid>https://orcid.org/0009-0006-9615-7468</orcidid><orcidid>https://orcid.org/0000-0001-9198-4778</orcidid><orcidid>https://orcid.org/0000-0002-6829-1452</orcidid></search><sort><creationdate>20240322</creationdate><title>Termination of convulsion seizures by destabilizing and perturbing seizure memory engrams</title><author>Lai, Shirong ; Zhang, Libo ; Tu, Xinyu ; Ma, Xinyue ; Song, Yujing ; Cao, Kexin ; Li, Miaomiao ; Meng, Jihong ; Shi, Yiqiang ; Wu, Qing ; Yang, Chen ; Lan, Zifan ; Lau, Chunyue Geoffrey ; Shi, Jie ; Ma, Weining ; Li, Shaoyi ; Xue, Yan-Xue ; Huang, Zhuo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c346t-6d37e92b5888ebe24f57bf461887f97239546e21c036aa74cdce9bf7adce4a303</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Animals</topic><topic>Electroencephalography</topic><topic>Epilepsy</topic><topic>Humans</topic><topic>Mammals</topic><topic>Neuroscience</topic><topic>SciAdv r-articles</topic><topic>Seizures - etiology</topic><topic>Sirolimus</topic><topic>TOR Serine-Threonine Kinases</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lai, Shirong</creatorcontrib><creatorcontrib>Zhang, Libo</creatorcontrib><creatorcontrib>Tu, Xinyu</creatorcontrib><creatorcontrib>Ma, Xinyue</creatorcontrib><creatorcontrib>Song, Yujing</creatorcontrib><creatorcontrib>Cao, Kexin</creatorcontrib><creatorcontrib>Li, Miaomiao</creatorcontrib><creatorcontrib>Meng, Jihong</creatorcontrib><creatorcontrib>Shi, Yiqiang</creatorcontrib><creatorcontrib>Wu, Qing</creatorcontrib><creatorcontrib>Yang, Chen</creatorcontrib><creatorcontrib>Lan, Zifan</creatorcontrib><creatorcontrib>Lau, Chunyue Geoffrey</creatorcontrib><creatorcontrib>Shi, Jie</creatorcontrib><creatorcontrib>Ma, Weining</creatorcontrib><creatorcontrib>Li, Shaoyi</creatorcontrib><creatorcontrib>Xue, Yan-Xue</creatorcontrib><creatorcontrib>Huang, Zhuo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Science advances</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lai, Shirong</au><au>Zhang, Libo</au><au>Tu, Xinyu</au><au>Ma, Xinyue</au><au>Song, Yujing</au><au>Cao, Kexin</au><au>Li, Miaomiao</au><au>Meng, Jihong</au><au>Shi, Yiqiang</au><au>Wu, Qing</au><au>Yang, Chen</au><au>Lan, Zifan</au><au>Lau, Chunyue Geoffrey</au><au>Shi, Jie</au><au>Ma, Weining</au><au>Li, Shaoyi</au><au>Xue, Yan-Xue</au><au>Huang, Zhuo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Termination of convulsion seizures by destabilizing and perturbing seizure memory engrams</atitle><jtitle>Science advances</jtitle><addtitle>Sci Adv</addtitle><date>2024-03-22</date><risdate>2024</risdate><volume>10</volume><issue>12</issue><spage>eadk9484</spage><epage>eadk9484</epage><pages>eadk9484-eadk9484</pages><issn>2375-2548</issn><eissn>2375-2548</eissn><abstract>Epileptogenesis, arising from alterations in synaptic strength, shares mechanistic and phenotypic parallels with memory formation. 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| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Animals Electroencephalography Epilepsy Humans Mammals Neuroscience SciAdv r-articles Seizures - etiology Sirolimus TOR Serine-Threonine Kinases |
| title | Termination of convulsion seizures by destabilizing and perturbing seizure memory engrams |
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