The Brahma-related gene 1 (Brg1) encodes the catalytic subunit of the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex, which regulates gene expression by relaxing chromatin structure, allowing greater access to transcription factors and repressors. Although the involvement of SWI/SNF-regulated genes in conditions such as autism spectrum disorder and epilepsy has been established, the specific contribution of Brg1 to epileptogenesis has not been well characterized. Using various tools, including pharmacological treatment, genomic manipulation with the CRISPR/Cas9 system in vivo, RNA sequencing, calcium imaging, and behavioral analysis, we investigated the function of Brg1 in the context of epilepsy. We discovered that disruption of Brg1 induces seizure-like behavior, increasing brain activity in zebrafish larvae. Delving deeper into the molecular underpinnings, we found that this is attributed to an imbalance between glutamatergic and GABAergic transmission. Transcriptomic analysis also highlighted differentially expressed genes related to the GABAergic synapse and the neurotransmitter vesicle cycle pathways. Finally, Brg1 disruption induces an inflammatory response and microglia activation that lead to neuronal death when the inhibition is prolonged. In conclusion, our findings indicate that Brg1 plays a pivotal role in the onset of seizures, exerting an impact on synaptic transmission. This underscores Brg1 as a potential therapeutic target for epilepsy.The research was financed under the NCN MAESTRO grant 2020/38/A/NZ3/00447 project.