GABA neuronal deletion of Shank3 exons 14–16 in mice suppresses striatal excitatory synaptic input and induces social and locomotor abnormalities

Taesun Yoo, Heejin Cho, Jiseok Lee, Haram Park, Ye Eun Yoo, Esther Yang, Jin Yong Kim, Hyun Kim, Eunjoon Kim

    Research output: Contribution to journalArticlepeer-review

    36 Citations (Scopus)

    Abstract

    Shank3 is an excitatory postsynaptic scaffolding protein implicated in multiple brain disorders, including autism spectrum disorders (ASD) and Phelan-McDermid syndrome (PMS). Although previous neurobiological studies on Shank3 and Shank3-mutant mice have revealed diverse roles of Shank3 in the regulation of synaptic, neuronal and brain functions, whether Shank3 expression in specific cell types distinctly contributes to mouse phenotypes remains largely unclear. In the present study, we generated two Shank3-mutant mouse lines (exons 14–16) carrying global and GABA neuron-specific deletions and characterized their electrophysiological and behavioral phenotypes. These mouse lines show similar decreases in excitatory synaptic input onto dorsolateral striatal neurons. In addition, the abnormal social and locomotor behaviors observed in global Shank3-mutant mice are strongly mimicked by GABA neuron-specific Shank3-mutant mice, whereas the repetitive and anxiety-like behaviors are only partially mimicked. These results suggest that GABAergic Shank3 (exons 14–16) deletion has strong influences on striatal excitatory synaptic transmission and social and locomotor behaviors in mice.

    Original languageEnglish
    Article number341
    JournalFrontiers in Cellular Neuroscience
    Volume12
    DOIs
    Publication statusPublished - 2018 Oct 9

    Bibliographical note

    Publisher Copyright:
    © 2018 Yoo, Cho, Lee, Park, Yoo, Yang, Kim, Kim and Kim.

    Keywords

    • Autism
    • Phelan-McDermid syndrome
    • Repetitive behavior
    • Shank3
    • Social interaction
    • Striatum

    ASJC Scopus subject areas

    • Cellular and Molecular Neuroscience

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