Inhibiting astrocyte calcium dynamics terminates status epilepticus via wireless septal stimulation.

Abstract

Status epilepticus (SE) is an acute medical emergency with unclear cellular and circuit mechanisms, and it is imperative to develop anti-SE strategies. Here, we observe distinct astrocytic Caactivity patterns during SE: generalized seizures (GS) show synchronized activity between CA3 and contralateral S1, while focal seizures (FS) exhibit desynchronization. Additionally, micrometer-scale wireless electrical stimulation (WES) targeting the medial septum and ventral diagonal band of Broca (MS/vDB) effectively terminates SE and suppresses abnormal astrocytic Caactivity, comparable to conventional deep brain stimulation (DBS). The effect is linked to MS/vDB GABAergic neuron activation, which suppresses calcium dynamics within the CA3 astrocyte-pyramidal neuron microcircuit. Meanwhile, WES of the MS/vDB effectively suppresses chronic spontaneous seizures induced by pilocarpine within 10 days. This study shows the divergent patterns of astrocytic activity during SE. It also demonstrates that WES of MS/vDB can effectively suppress SE, establishing an advanced therapeutic strategy.