Selective magnetoelectric stimulation antagonizes GABAA receptors subunit in the left prelimbic cortex neurons to alleviate schizophrenia-like behaviors

Schizophrenia (SCZ) is a prevalent and disabling mental disorder. Clinically, its complex symptoms, including negative symptoms and cognitive impairments, can be ameliorated using electromagnetic techniques such as repetitive transcranial magnetic stimulation (rTMS). To investigate the neural mechanisms of magnetic stimulation and identify selective therapeutic targets, we employed a combined magnetic stimulation system treatment (c-MSST). Targeting the mouse left prelimbic cortex (PrL) with c-MSST reversed SCZ-like behaviors and dendritic spine density reductions induced by MK-801 injection. SCZ-like mice showed a region-specific increase in Gabre (gamma-aminobutyric acid type A receptor subunit epsilon) in the left PrL, normalized by c-MSST. Specific Gabre knockdown in the left PrL reversed SCZ-like behaviors induced by MK-801. Additionally, the transgenic mouse with Gabre knock-in specific to the PrL exhibited SCZ-like behaviors and synaptic plasticity deficits, both reversed by c-MSST. Overexpression of the p62 gene disrupted Gabarap and Gabarapl1 binding, reducing Gabre surface expression. Our findings suggest Gabre and related circuits as promising targets for schizophrenia treatment.