Depolarization block paradoxically drives surges of neurotransmitter release during seizure activity
OBJECTIVE: This study was undertaken to investigate the mechanisms underlying the paradoxical phenomena of excessive neurotransmitter release and suppressed sodium-spike generation due to depolarization block (DB) during seizure activity. METHODS: puff was applied to induce DB and monitor glutamate and dopamine release. Additionally, we examined dopamine release in the neocortex during kindling-evoked seizures following acute lesions of dopaminergic axons in the medial forebrain bundle in vivo. RESULTS: puff or during EA. In animals with bilateral medial forebrain bundle lesions, dopamine release in neocortex was largely preserved during kindling-evoked seizures. SIGNIFICANCE: rises and subsequent axonal DB may trigger neurotransmitter surges during epileptic seizures, providing a novel mechanistic insight into seizure-related neurotransmitter dynamics and a possible explanation for severe epilepsy-associated neuropsychiatric comorbidities.
Authors
- Wenqing Shui (ORCID: https://orcid.org/0000-0002-5245-2477)
- Haidong Lu (ORCID: https://orcid.org/0000-0003-1739-9508)
- Suixin Deng (ORCID: https://orcid.org/0000-0003-4795-2570)
- Yuandong Liu (ORCID: https://orcid.org/0000-0002-0274-130X)
- Quansheng He
- Zongyi Xu (ORCID: https://orcid.org/0000-0002-8267-6834)
- Liang Li (ORCID: https://orcid.org/0000-0002-6836-042X)
- Xiaoxue Zhang (ORCID: https://orcid.org/0000-0001-5246-6345)
- Shidi Wang
- Shuyu Yuan
- H Guo
- Kexin Wang (ORCID: https://orcid.org/0009-0001-1654-2926)
- Wei Duan (ORCID: https://orcid.org/0009-0006-7045-9935)
- Yousheng Shu (ORCID: https://orcid.org/0000-0002-2834-2876)
- Yang Tian (ORCID: https://orcid.org/0000-0001-8850-0349)
- Wei Ke (ORCID: https://orcid.org/0009-0002-8248-4338)
- Wanrui Li (ORCID: https://orcid.org/0009-0004-5450-7541)
Institutions
- Qingdao University (CN)
- Central South University (CN)
- ShanghaiTech University (CN)
- Shanghai Children's Hospital (CN)
- Huashan Hospital (CN)
- Ministry of Education and Child Care (CA)
- East China Normal University (CN)
Publication Details
- Journal
- Epilepsia
- Published
- 2026-05-11
- DOI
- https://doi.org/10.1002/epi.70280
- Primary Topic
- Neuroscience and Neuropharmacology Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- Program of Shanghai Academic Research Leader