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 journalArticlepeer-review

142 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

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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