Our study is the first to define key aspects of acute neuronal dysregulation in this important genetic model of Pik3ca-driven epilepsy, and demonstrates these mechanisms are distinct from synaptic and network-related mechanisms reported in MTOR, TSC, and RHEB epilepsy models (Crino, 2016; Kim and Lee, 2019; Stafstrom, 2019; Hsieh et al., 2020) with PI3K pathway dysregulation. Here, TSC1 is linked to epilepsy.