Postnatal development of a GABA deficit and disturbance of neural functions in mice lacking GAD65

Oliver Stork, Feng Yun Ji, Koichi Kaneko, Simone Stork, Yuko Yoshinobu, Takahiro Moriya, Shigenobu Shibata, Kunihiko Obata

    Research output: Contribution to journalArticle

    138 Citations (Scopus)

    Abstract

    The 65-kDa isoform of glutamic acid decarboxylase (GAD65) is believed to play an essential role for GABA synthesis in the central nervous system. Using mice with targeted disruption of the GAD65 gene (GAD65(-/-) mice) we investigated the contribution of GAD65 to GABA synthesis in different brain areas during postnatal development and in adulthood. In the amygdala, hypothalamus and parietal cortex of GAD65(+/+) mice an increase of GABA levels was observed during postnatal development, most prominently between the first and second month after birth. This increase appeared to be dependent on GAD65, as it was delayed by 2 months in GAD65(+/-) mice and was not observed in GAD65(-/-) mice. Likely as a consequence of their GABA deficit, adult GAD65(-/-) mice showed a largely abnormal neural activity with frequent paroxysmal discharges and spontaneous seizures. They furthermore displayed increased anxiety-like behaviour in a light/dark avoidance test and reduced intermale aggression, as well as a reduced forced-swimming-induced immobility indicative of an antidepressant-like behavioural change. Adult GAD65(+/-) mice did not show behavioural disturbances except for a reduced aggressive behaviour that was comparable to that in GAD65(-/-) mice. We conclude that GAD65-mediated GABA synthesis may be crucially involved in control of emotional behaviour and indispensable for a tonic inhibition that prevents the development of hyperexcitability in the maturating central nervous system. Aggressive, and possibly other social behaviour may be especially prone to regulation through GAD65-mediated GABA synthesis. (C) 2000 Elsevier Science B.V.

    Original languageEnglish
    Pages (from-to)45-58
    Number of pages14
    JournalBrain Research
    Volume865
    Issue number1
    DOIs
    Publication statusPublished - 2000 May 19

    Fingerprint

    gamma-Aminobutyric Acid
    Central Nervous System
    Parietal Lobe
    Behavior Control
    Glutamate Decarboxylase
    Social Behavior
    Amygdala
    Aggression
    Antidepressive Agents
    Hypothalamus
    Protein Isoforms
    Seizures
    Anxiety
    Parturition
    Light
    Brain
    Genes

    Keywords

    • Amygdala
    • Emotional behaviour
    • Hypothalamus
    • Knock out mouse
    • Seizure

    ASJC Scopus subject areas

    • Neuroscience(all)

    Cite this

    Stork, O., Ji, F. Y., Kaneko, K., Stork, S., Yoshinobu, Y., Moriya, T., ... Obata, K. (2000). Postnatal development of a GABA deficit and disturbance of neural functions in mice lacking GAD65. Brain Research, 865(1), 45-58. https://doi.org/10.1016/S0006-8993(00)02206-X

    Postnatal development of a GABA deficit and disturbance of neural functions in mice lacking GAD65. / Stork, Oliver; Ji, Feng Yun; Kaneko, Koichi; Stork, Simone; Yoshinobu, Yuko; Moriya, Takahiro; Shibata, Shigenobu; Obata, Kunihiko.

    In: Brain Research, Vol. 865, No. 1, 19.05.2000, p. 45-58.

    Research output: Contribution to journalArticle

    Stork, O, Ji, FY, Kaneko, K, Stork, S, Yoshinobu, Y, Moriya, T, Shibata, S & Obata, K 2000, 'Postnatal development of a GABA deficit and disturbance of neural functions in mice lacking GAD65', Brain Research, vol. 865, no. 1, pp. 45-58. https://doi.org/10.1016/S0006-8993(00)02206-X
    Stork, Oliver ; Ji, Feng Yun ; Kaneko, Koichi ; Stork, Simone ; Yoshinobu, Yuko ; Moriya, Takahiro ; Shibata, Shigenobu ; Obata, Kunihiko. / Postnatal development of a GABA deficit and disturbance of neural functions in mice lacking GAD65. In: Brain Research. 2000 ; Vol. 865, No. 1. pp. 45-58.
    @article{ebb028bb97f14273832e333894508479,
    title = "Postnatal development of a GABA deficit and disturbance of neural functions in mice lacking GAD65",
    abstract = "The 65-kDa isoform of glutamic acid decarboxylase (GAD65) is believed to play an essential role for GABA synthesis in the central nervous system. Using mice with targeted disruption of the GAD65 gene (GAD65(-/-) mice) we investigated the contribution of GAD65 to GABA synthesis in different brain areas during postnatal development and in adulthood. In the amygdala, hypothalamus and parietal cortex of GAD65(+/+) mice an increase of GABA levels was observed during postnatal development, most prominently between the first and second month after birth. This increase appeared to be dependent on GAD65, as it was delayed by 2 months in GAD65(+/-) mice and was not observed in GAD65(-/-) mice. Likely as a consequence of their GABA deficit, adult GAD65(-/-) mice showed a largely abnormal neural activity with frequent paroxysmal discharges and spontaneous seizures. They furthermore displayed increased anxiety-like behaviour in a light/dark avoidance test and reduced intermale aggression, as well as a reduced forced-swimming-induced immobility indicative of an antidepressant-like behavioural change. Adult GAD65(+/-) mice did not show behavioural disturbances except for a reduced aggressive behaviour that was comparable to that in GAD65(-/-) mice. We conclude that GAD65-mediated GABA synthesis may be crucially involved in control of emotional behaviour and indispensable for a tonic inhibition that prevents the development of hyperexcitability in the maturating central nervous system. Aggressive, and possibly other social behaviour may be especially prone to regulation through GAD65-mediated GABA synthesis. (C) 2000 Elsevier Science B.V.",
    keywords = "Amygdala, Emotional behaviour, Hypothalamus, Knock out mouse, Seizure",
    author = "Oliver Stork and Ji, {Feng Yun} and Koichi Kaneko and Simone Stork and Yuko Yoshinobu and Takahiro Moriya and Shigenobu Shibata and Kunihiko Obata",
    year = "2000",
    month = "5",
    day = "19",
    doi = "10.1016/S0006-8993(00)02206-X",
    language = "English",
    volume = "865",
    pages = "45--58",
    journal = "Brain Research",
    issn = "0006-8993",
    publisher = "Elsevier",
    number = "1",

    }

    TY - JOUR

    T1 - Postnatal development of a GABA deficit and disturbance of neural functions in mice lacking GAD65

    AU - Stork, Oliver

    AU - Ji, Feng Yun

    AU - Kaneko, Koichi

    AU - Stork, Simone

    AU - Yoshinobu, Yuko

    AU - Moriya, Takahiro

    AU - Shibata, Shigenobu

    AU - Obata, Kunihiko

    PY - 2000/5/19

    Y1 - 2000/5/19

    N2 - The 65-kDa isoform of glutamic acid decarboxylase (GAD65) is believed to play an essential role for GABA synthesis in the central nervous system. Using mice with targeted disruption of the GAD65 gene (GAD65(-/-) mice) we investigated the contribution of GAD65 to GABA synthesis in different brain areas during postnatal development and in adulthood. In the amygdala, hypothalamus and parietal cortex of GAD65(+/+) mice an increase of GABA levels was observed during postnatal development, most prominently between the first and second month after birth. This increase appeared to be dependent on GAD65, as it was delayed by 2 months in GAD65(+/-) mice and was not observed in GAD65(-/-) mice. Likely as a consequence of their GABA deficit, adult GAD65(-/-) mice showed a largely abnormal neural activity with frequent paroxysmal discharges and spontaneous seizures. They furthermore displayed increased anxiety-like behaviour in a light/dark avoidance test and reduced intermale aggression, as well as a reduced forced-swimming-induced immobility indicative of an antidepressant-like behavioural change. Adult GAD65(+/-) mice did not show behavioural disturbances except for a reduced aggressive behaviour that was comparable to that in GAD65(-/-) mice. We conclude that GAD65-mediated GABA synthesis may be crucially involved in control of emotional behaviour and indispensable for a tonic inhibition that prevents the development of hyperexcitability in the maturating central nervous system. Aggressive, and possibly other social behaviour may be especially prone to regulation through GAD65-mediated GABA synthesis. (C) 2000 Elsevier Science B.V.

    AB - The 65-kDa isoform of glutamic acid decarboxylase (GAD65) is believed to play an essential role for GABA synthesis in the central nervous system. Using mice with targeted disruption of the GAD65 gene (GAD65(-/-) mice) we investigated the contribution of GAD65 to GABA synthesis in different brain areas during postnatal development and in adulthood. In the amygdala, hypothalamus and parietal cortex of GAD65(+/+) mice an increase of GABA levels was observed during postnatal development, most prominently between the first and second month after birth. This increase appeared to be dependent on GAD65, as it was delayed by 2 months in GAD65(+/-) mice and was not observed in GAD65(-/-) mice. Likely as a consequence of their GABA deficit, adult GAD65(-/-) mice showed a largely abnormal neural activity with frequent paroxysmal discharges and spontaneous seizures. They furthermore displayed increased anxiety-like behaviour in a light/dark avoidance test and reduced intermale aggression, as well as a reduced forced-swimming-induced immobility indicative of an antidepressant-like behavioural change. Adult GAD65(+/-) mice did not show behavioural disturbances except for a reduced aggressive behaviour that was comparable to that in GAD65(-/-) mice. We conclude that GAD65-mediated GABA synthesis may be crucially involved in control of emotional behaviour and indispensable for a tonic inhibition that prevents the development of hyperexcitability in the maturating central nervous system. Aggressive, and possibly other social behaviour may be especially prone to regulation through GAD65-mediated GABA synthesis. (C) 2000 Elsevier Science B.V.

    KW - Amygdala

    KW - Emotional behaviour

    KW - Hypothalamus

    KW - Knock out mouse

    KW - Seizure

    UR - http://www.scopus.com/inward/record.url?scp=0034685841&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=0034685841&partnerID=8YFLogxK

    U2 - 10.1016/S0006-8993(00)02206-X

    DO - 10.1016/S0006-8993(00)02206-X

    M3 - Article

    C2 - 10814732

    AN - SCOPUS:0034685841

    VL - 865

    SP - 45

    EP - 58

    JO - Brain Research

    JF - Brain Research

    SN - 0006-8993

    IS - 1

    ER -