Modulation of GABAergic neurons in acute epilepsy using sonogenetics

Abstract

Epilepsy, a neurological disorder caused by hypersynchronous neural disturbances, has traditionally been treated with surgery, pharmacotherapy, and neuromodulation techniques such as deep brain stimulation and vagus nerve stimulation. However, these methods are often limited by invasiveness, off-target effects, and poor resolution. We present a noninvasive alternative utilizing sonogenetics to selectively stimulate γ-aminobutyric acid (GABA)ergic neurons in the amygdala through engineered auditory-sensing protein, mPrestin (N7T, N308S), in a pentylenetetrazole-induced rat model. Activation of GABAergic neurons induced by the sonication with 0.5-MHz transcranial ultrasound can modulate epileptiform activity by 50 %. Electrophysiological recordings confirmed effective neuromodulation and persistent seizure suppression up to 60 min post-treatment without tissue damage, inflammation, or apoptosis. This sonogenetic approach offers a promising, safe method for epilepsy management by targeting GABAergic neurons.