Developmental excitatory-to-inhibitory GABA-polarity switch is disrupted in 22q11.2 deletion syndrome: a potential target for clinical therapeutics.

ABSTRACT: Individuals with 22q11.2 microdeletion syndrome (22q11.2 DS) show cognitive and behavioral dysfunctions, developmental delays in childhood and risk of developing schizophrenia and autism. Despite extensive previous studies in adult animal models, a possible embryonic root of this syndrome has not been determined. Here, in neurons from a 22q11.2 DS mouse model (Lgdel +/-), we found embryonic-premature alterations in the neuronal chloride cotransporters indicated by dysregulated NKCC1 and KCC2 protein expression levels. We demonstrate with large-scale spiking activity recordings a concurrent deregulation of the spontaneous network activity and homeostatic network plasticity. Additionally, Lgdel +/- networks at early development show abnormal neuritogenesis and void of synchronized spontaneou

SUBMITTER: Amin H 

PROVIDER: S-EPMC5691208 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature