Expression of GCaMP6s in the dentate gyrus induces tonic–clonic seizures

• Published in: Scientific reports 2024-04, Vol.14 (1), p.8104-8104, Article 8104
• Main Authors: Teng, Sasa, Wang, Wanqi, Wen, Jia Jun Joel, Wang, Jingxuan, Turi, Gergely F., Peng, Yueqing
• Format: Article
• Language: English
• Subjects: 631/378/1595/1554; 631/378/1689/178; Brain slice preparation; Ca2; Calcium; Calcium (intracellular); Calcium - metabolism; Calcium buffering; Calcium imaging; Calcium Signaling; Calcium signalling; Calcium, Dietary - metabolism; Convulsions & seizures; Dentate gyrus; Dentate Gyrus - metabolism; EEG; Electrophysiology; Epilepsy; Excitability; GCaMP6s; Granule cells; Humanities and Social Sciences; Humans; Intracellular; Intracellular signalling; multidisciplinary; Neurons - metabolism; Science; Science (multidisciplinary); Seizures; Seizures - genetics; Seizures - metabolism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-58819-9

GCaMP is a genetically encoded calcium indicator (GECI) widely used in neuroscience research. It measures intracellular Ca 2+ level by fluorescence changes as it directly binds to Ca 2+ . In this process, the effect of this calcium buffer on the intracellular calcium signaling and cell physiology is often not taken into consideration. However, growing evidence from calcium imaging studies shows GCaMP expression under certain conditions can generate aberrant activity, such as seizures. In this study, we examined the effect of GCaMP6 expression in the dentate gyrus (DG) on epileptogenesis. We found that viral expression of GCaMP6s but not GCaMP6f in the DG induces tonic–clonic seizures several weeks after viral injection. Cell-type specific expression of GCaMP6s revealed the granule cells (GCs) as the key player in GCaMP6s-induced epilepsy. Finally, by using slice electrophysiology, we demonstrated that GCaMP6s expression increases neuronal excitability in the GCs. Together, this study highlights the ability of GCaMP6s in DG-associated epileptogenesis.