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Inhibitory interneurons mediate autism-associated behaviors via 4E-BP2.

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2019

Proc Natl Acad Sci U S A. 2019 Sep 3;116(36):18060-18067. doi: 10.1073/pnas.1908126116. Epub 2019 Aug 19.

Inhibitory interneurons mediate autism-associated behaviors via 4E-BP2.

S Wiebe;A Nagpal;VT Truong;J Park;A Skalecka;AJ He;K Gamache;A Khoutorsky;I Gantois;N Sonenberg

McGill University, Montreal, QC H3G 1Y6, Canada

Service type: Knockout mice

Abstract

Translational control plays a key role in regulation of neuronal activity and behavior. Deletion of the translational repressor 4E-BP2 in mice alters excitatory and inhibitory synaptic functions, engendering autistic-like behaviors. The contribution of 4E-BP2-dependent translational control in excitatory and inhibitory neurons and astrocytic cells to these behaviors remains unknown. To investigate this, we generated cell-type-specific conditional 4E-BP2 knockout mice and tested them for the salient features of autism, including repetitive stereotyped behaviors (self-grooming and marble burying), sociability (3-chamber social and direct social interaction tests), and communication (ultrasonic vocalizations in pups). We found that deletion of 4E-BP2 in GABAergic inhibitory neurons, defined by Gad2, resulted in impairments in social interaction and vocal communication. In contrast, deletion of 4E-BP2 in forebrain glutamatergic excitatory neurons, defined by Camk2a, or in astrocytes, defined by Gfap, failed to cause autistic-like behavioral abnormalities. Taken together, we provide evidence for an inhibitory-cell-specific role of 4E-BP2 in engendering autism-related behaviors.

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