Kang E, Song J, Lin Y, Park J, Lee JH, Hussani Q, Gu Y, Ge S, Li W, Hsu KS, Berninger B, Christian KM, Song H, Ming GL (2019) Interplay between a Mental Disorder Risk Gene and Developmental Polarity Switch of GABA Action Leads to Excitation-Inhibition Imbalance. Cell Rep 28: 1419-1428.e3

Excitation-inhibition (E-I) imbalance is considered a hallmark of various neurodevelopmental disorders, including schizophrenia and autism. How genetic risk factors disrupt coordinated glutamatergic and GABAergic synapse formation to cause an E-I imbalance is not well understood. Here, we show that knockdown of Disrupted-in-schizophrenia 1 (DISC1), a risk gene for major mental disorders, leads to E-I imbalance in mature dentate granule neurons. We found that excessive GABAergic inputs from parvalbumin-, but not somatostatin-, expressing interneurons enhance the formation of both glutamatergic and GABAergic synapses in immature mutant neurons. Following the switch in GABAergic signaling polarity from depolarizing to hyperpolarizing during neuronal maturation, heightened inhibition from excessive parvalbumin

Pubmed: 31390557