Overexpression of neuregulin 1 in GABAergic interneurons results in reversible cortical disinhibition.

ABSTRACT: Cortical disinhibition is a common feature of several neuropsychiatric diseases such as schizophrenia, autism and intellectual disabilities. However, the underlying mechanisms are not fully understood. To mimic increased expression of Nrg1, a schizophrenia susceptibility gene in GABAergic interneurons from patients with schizophrenia, we generated gtoNrg1 mice with overexpression of Nrg1 in GABAergic interneurons. gtoNrg1 mice showed cortical disinhibition at the cellular, synaptic, neural network and behavioral levels. We revealed that the intracellular domain of NRG1 interacts with the cytoplasmic loop 1 of Na_v1.1, a sodium channel critical for the excitability of GABAergic interneurons, and inhibits Na_v currents. Intriguingly, activation of GABAergic interneurons o

SUBMITTER: Wang YY 

PROVIDER: S-EPMC7804852 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature