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  3. Chemogenetic silencing of the subiculum blocks acute chronic temporal lobe epilepsy

Chemogenetic silencing of the subiculum blocks acute chronic temporal lobe epilepsy

  • Mol Brain. 2024 Nov 29;17(1):91. doi: 10.1186/s13041-024-01164-9.
Jianbang Lin 1 2,  Jing Liu 1 3,  Qi Zhang 4,  Taian Liu 1,  Zexuan Hong 1 3,  Yi Lu 1 2,  Cheng Zhong 1 2,  Zhonghua Lu 1 2 5,  Yuantao Li 6 7,  Yu Hu 8
Affiliations

Affiliations

  • 1 Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
  • 2 University of Chinese Academy of Sciences, Beijing, 100049, China.
  • 3 Department of Anesthesiology, Affiliated Shenzhen Maternity & Child Healthcare Hospital, Southern Medical University, Shenzhen, 518027, China.
  • 4 Department of Medicinal Chemistry and Natural Medicine Chemistry, College of Pharmacy, Harbin Medical University, Harbin, 150081, China.
  • 5 The Key Laboratory of Biomedical Imaging Science and System, Chinese Academy of Sciences, Shenzhen, 518055, China.
  • 6 Department of Anesthesiology, Affiliated Shenzhen Maternity & Child Healthcare Hospital, Southern Medical University, Shenzhen, 518027, China. szmchlyt@smu.edu.cn.
  • 7 Biomedical Research Institute, Hubei University of Medicine, Shiyan, 442000, China. szmchlyt@smu.edu.cn.
  • 8 Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China. yu.hu@siat.ac.cn.
PMID: 39614352 DOI: 10.1186/s13041-024-01164-9
Abstract

Temporal lobe epilepsy (TLE) is the most common form of medically-intractable epilepsy. Subicular hyperexcitability is frequently observed with TLE, presumably caused by impaired inhibition of local excitatory neurons. Here, we evaluated the effectiveness of silencing subicular pyramidal neurons to treat a rodent model of TLE. First, we generated a chronic TLE mouse model via initial intrahippocampal kainic acid (IHKA) injection. In the chronic state after first IHKA injection, behavioral seizures and histological abnormalities were reliably observed. We then injected an adeno-associated viral (AAV) vector carrying an inhibitory chemogenetic element, hM4Di, directly into the subiculum. Eight weeks after the first IHKA injection, acute seizures were induced by giving a second dose of kainic acid (KA), which mimicked generalized tonic-clonic seizures. Herein, precise control over generalized tonic-clonic seizure onset was achieved via this two-step process. We found that chemogenetic suppression of subicular pyramidal neurons had a robust anti-epileptogenesis effect in this acute-chronic model of TLE. These data confirm a crucial role of the subiculum in the propagation of hippocampal seizures and highlight the potential for using subicular chemogenetic manipulation to treat generalized tonic-clonic seizures.

Keywords

Chemogenetic; Generalized tonic–clonic seizures; Kainic acid; Subiculum; Temporal lobe epilepsy.

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