Protocol to downregulate GABAergic-astrocyte signaling via astrocyte-selective ablation of GABA(B) receptor in adult mice

Here, we present a protocol to selectively downregulate GABA(B) receptor (GABA(B)R) expression in astrocytes of mouse medial prefrontal cortex (mPFC). We first describe the procedure of surgeries and viral injections. We then detail genetic, histological, and functional characterizations of astrocytic GABA(B)R ablation using RT-PCR, imaging, and behavioral assays. The use of GABA(B) flox mice can be easily adapted to generate astrocyte-selective GABA(B)R ablation in different brain areas and postnatal stages, leading to local downregulation of GABAergic-astrocyte signaling without developmental issues. For complete details on the use and execution of this protocol, please refer to Mederos et al. (2021).