Transient targeting of hypothalamic orexin neurons alleviates seizures in a mouse model of epilepsy
Abstract Lateral hypothalamic (LH) hypocretin/orexin neurons (HONs) control brain-wide electrical excitation. Abnormally high excitation produces epileptic seizures, which affect millions of people and need better treatments. HON population activity spikes from minute to minute, but the role of this...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-45515-5 |
| _version_ | 1797273932687998976 |
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| author | Han-Tao Li Paulius Viskaitis Eva Bracey Daria Peleg-Raibstein Denis Burdakov |
| author_facet | Han-Tao Li Paulius Viskaitis Eva Bracey Daria Peleg-Raibstein Denis Burdakov |
| author_sort | Han-Tao Li |
| collection | DOAJ |
| description | Abstract Lateral hypothalamic (LH) hypocretin/orexin neurons (HONs) control brain-wide electrical excitation. Abnormally high excitation produces epileptic seizures, which affect millions of people and need better treatments. HON population activity spikes from minute to minute, but the role of this in seizures is unknown. Here, we describe correlative and causal links between HON activity spikes and seizures. Applying temporally-targeted HON recordings and optogenetic silencing to a male mouse model of acute epilepsy, we found that pre-seizure HON activity predicts and controls the electrophysiology and behavioral pathology of subsequent seizures. No such links were detected for HON activity during seizures. Having thus defined the time window where HONs influence seizures, we targeted it with LH deep brain stimulation (DBS), which inhibited HON population activity, and produced seizure protection. Collectively, these results uncover a feature of brain activity linked to seizures, and demonstrate a proof-of-concept treatment that controls this feature and alleviates epilepsy. |
| first_indexed | 2024-03-07T14:51:12Z |
| format | Article |
| id | doaj.art-199cc29e2be84e878ed018bd72d8768d |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-07T14:51:12Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-199cc29e2be84e878ed018bd72d8768d2024-03-05T19:39:23ZengNature PortfolioNature Communications2041-17232024-02-0115111210.1038/s41467-024-45515-5Transient targeting of hypothalamic orexin neurons alleviates seizures in a mouse model of epilepsyHan-Tao Li0Paulius Viskaitis1Eva Bracey2Daria Peleg-Raibstein3Denis Burdakov4Department of Health Sciences and Technology, Swiss Federal Institute of Technology | ETH ZurichDepartment of Health Sciences and Technology, Swiss Federal Institute of Technology | ETH ZurichDepartment of Health Sciences and Technology, Swiss Federal Institute of Technology | ETH ZurichDepartment of Health Sciences and Technology, Swiss Federal Institute of Technology | ETH ZurichDepartment of Health Sciences and Technology, Swiss Federal Institute of Technology | ETH ZurichAbstract Lateral hypothalamic (LH) hypocretin/orexin neurons (HONs) control brain-wide electrical excitation. Abnormally high excitation produces epileptic seizures, which affect millions of people and need better treatments. HON population activity spikes from minute to minute, but the role of this in seizures is unknown. Here, we describe correlative and causal links between HON activity spikes and seizures. Applying temporally-targeted HON recordings and optogenetic silencing to a male mouse model of acute epilepsy, we found that pre-seizure HON activity predicts and controls the electrophysiology and behavioral pathology of subsequent seizures. No such links were detected for HON activity during seizures. Having thus defined the time window where HONs influence seizures, we targeted it with LH deep brain stimulation (DBS), which inhibited HON population activity, and produced seizure protection. Collectively, these results uncover a feature of brain activity linked to seizures, and demonstrate a proof-of-concept treatment that controls this feature and alleviates epilepsy.https://doi.org/10.1038/s41467-024-45515-5 |
| spellingShingle | Han-Tao Li Paulius Viskaitis Eva Bracey Daria Peleg-Raibstein Denis Burdakov Transient targeting of hypothalamic orexin neurons alleviates seizures in a mouse model of epilepsy Nature Communications |
| title | Transient targeting of hypothalamic orexin neurons alleviates seizures in a mouse model of epilepsy |
| title_full | Transient targeting of hypothalamic orexin neurons alleviates seizures in a mouse model of epilepsy |
| title_fullStr | Transient targeting of hypothalamic orexin neurons alleviates seizures in a mouse model of epilepsy |
| title_full_unstemmed | Transient targeting of hypothalamic orexin neurons alleviates seizures in a mouse model of epilepsy |
| title_short | Transient targeting of hypothalamic orexin neurons alleviates seizures in a mouse model of epilepsy |
| title_sort | transient targeting of hypothalamic orexin neurons alleviates seizures in a mouse model of epilepsy |
| url | https://doi.org/10.1038/s41467-024-45515-5 |
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