IP3R1 deficiency in the cerebellum/brainstem causes basal ganglia-independent dystonia by triggering tonic Purkinje cell firings in mice

Chihiro Hisatsune, Hiroyuki Miyamoto, Moritoshi Hirono, Naohide Yamaguchi, Takeyuki Sugawara, Naoko Ogawa, Etsuko Ebisui, Toshio Ohshima, Masahisa Yamada, Takao K. Hensch, Mitsuharu Hattori, Katsuhiko Mikoshiba

    Research output: Contribution to journalArticle

    26 Citations (Scopus)

    Abstract

    The type 1 inositol 1,4,5- trisphosphate receptor (IP3R1) is a Ca2+ channel on the endoplasmic reticulum and is a predominant isoform in the brain among the three types of IP3Rs. Mice lacking IP3R1 show seizure-like behavior; however the cellular and neural circuit mechanism by which IP3R1 deletion causes the abnormal movements is unknown. Here, we found that the conditional knockout mice lacking IP3R1 specifically in the cerebellum and brainstem experience dystonia and show that cerebellar Purkinje cell (PC) firing patterns were coupled to specific dystonic movements. Recordings in freely behaving mice revealed epochs of low and high frequency PC complex spikes linked to body extension and rigidity, respectively. Remarkably, dystonic symptoms were independent of the basal ganglia, and could be rescued by inactivation of the cerebellum, inferior olive or in the absence of PCs. These findings implicate IP3R1-dependent PC firing patterns in cerebellum in motor coordination and the expression of dystonia through the olivo-cerebellar pathway.

    Original languageEnglish
    Article number156
    JournalFrontiers in Neural Circuits
    Volume7
    Issue numberOCT
    Publication statusPublished - 2013 Oct 4

    Fingerprint

    Dystonia
    Purkinje Cells
    Basal Ganglia
    Cerebellum
    Brain Stem
    Inositol 1,4,5-Trisphosphate Receptors
    Dyskinesias
    Knockout Mice
    Endoplasmic Reticulum
    Protein Isoforms
    Seizures
    Brain

    Keywords

    • Basal ganglia
    • Cerebellum
    • Complex spikes
    • Dystonia
    • Inferior olive
    • Inositol 1,4,5-trisphosphate
    • Purkinje cells
    • SCA15

    ASJC Scopus subject areas

    • Neuroscience (miscellaneous)
    • Cellular and Molecular Neuroscience
    • Sensory Systems
    • Cognitive Neuroscience
    • Medicine(all)

    Cite this

    Hisatsune, C., Miyamoto, H., Hirono, M., Yamaguchi, N., Sugawara, T., Ogawa, N., ... Mikoshiba, K. (2013). IP3R1 deficiency in the cerebellum/brainstem causes basal ganglia-independent dystonia by triggering tonic Purkinje cell firings in mice. Frontiers in Neural Circuits, 7(OCT), [156].

    IP3R1 deficiency in the cerebellum/brainstem causes basal ganglia-independent dystonia by triggering tonic Purkinje cell firings in mice. / Hisatsune, Chihiro; Miyamoto, Hiroyuki; Hirono, Moritoshi; Yamaguchi, Naohide; Sugawara, Takeyuki; Ogawa, Naoko; Ebisui, Etsuko; Ohshima, Toshio; Yamada, Masahisa; Hensch, Takao K.; Hattori, Mitsuharu; Mikoshiba, Katsuhiko.

    In: Frontiers in Neural Circuits, Vol. 7, No. OCT, 156, 04.10.2013.

    Research output: Contribution to journalArticle

    Hisatsune, C, Miyamoto, H, Hirono, M, Yamaguchi, N, Sugawara, T, Ogawa, N, Ebisui, E, Ohshima, T, Yamada, M, Hensch, TK, Hattori, M & Mikoshiba, K 2013, 'IP3R1 deficiency in the cerebellum/brainstem causes basal ganglia-independent dystonia by triggering tonic Purkinje cell firings in mice', Frontiers in Neural Circuits, vol. 7, no. OCT, 156.
    Hisatsune, Chihiro ; Miyamoto, Hiroyuki ; Hirono, Moritoshi ; Yamaguchi, Naohide ; Sugawara, Takeyuki ; Ogawa, Naoko ; Ebisui, Etsuko ; Ohshima, Toshio ; Yamada, Masahisa ; Hensch, Takao K. ; Hattori, Mitsuharu ; Mikoshiba, Katsuhiko. / IP3R1 deficiency in the cerebellum/brainstem causes basal ganglia-independent dystonia by triggering tonic Purkinje cell firings in mice. In: Frontiers in Neural Circuits. 2013 ; Vol. 7, No. OCT.
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