Microglial VRK2 Regulates Astrocytic GABA Synthesis and Tonic Inhibition in the Thalamus.

ABSTRACT: Vaccinia-related kinase 2 (VRK2) is a prominent genetic risk factor for neurodevelopmental disorders (NDDs), including schizophrenia and epilepsy, which are characterized by cognitive and behavioral impairments. The mediodorsal (MD) thalamus, a higher-order nucleus involved in executive function and social behavior, is frequently disrupted in these conditions. However, how VRK2 influences thalamic regulation remains unclear. Here, we show that Vrk2-deficient mice exhibit a significant reduction in tonic GABA currents in the MD thalamus, accompanied by decreased excitatory synaptic input but preserved intrinsic neuronal excitability. Although VRK2 is not expressed in astrocytes, its deletion impaired astrocyte-mediated tonic inhibition, suggesting a non-cell-autonomous mechanism. Single-cel

SUBMITTER: Lee D 

PROVIDER: S-EPMC12631724 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature