Loss and Gain of MeCP2 Cause Similar Hippocampal Circuit Dysfunction that Is Rescued by Deep Brain Stimulation in a Rett Syndrome Mouse Model.

ABSTRACT: Loss- and gain-of-function mutations in methyl-CpG-binding protein 2 (MECP2) underlie two distinct neurological syndromes with strikingly similar features, but the synaptic and circuit-level changes mediating these shared features are undefined. Here we report three novel signs of neural circuit dysfunction in three mouse models of MECP2 disorders (constitutive Mecp2 null, mosaic Mecp2(+/-), and MECP2 duplication): abnormally elevated synchrony in the firing activity of hippocampal CA1 pyramidal neurons, an impaired homeostatic response to perturbations of excitatory-inhibitory balance, and decreased excitatory synaptic response in inhibitory neurons. Conditional mutagenesis studies revealed that MeCP2 dysfunction in excitatory neurons mediated elevated synchrony at baseline, while MeCP2 d

SUBMITTER: Lu H 

PROVIDER: S-EPMC5019177 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature