Journal Article

A deficit of brain dystrophin impairs specific amygdala GABAergic transmission and enhances defensive behaviour in mice

Masayuki Sekiguchi, Ko Zushida, Mikiharu Yoshida, Motoko Maekawa, Sari Kamichi, Mizuko Yoshida, Yoshinori Sahara, Shigeki Yuasa, Shin'ichi Takeda and Keiji Wada

in Brain

Published on behalf of The Guarantors of Brain

Volume 132, issue 1, pages 124-135
Published in print January 2009 | ISSN: 0006-8950
Published online October 2009 | e-ISSN: 1460-2156 | DOI:
A deficit of brain dystrophin impairs specific amygdala GABAergic transmission and enhances defensive behaviour in mice

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Duchenne muscular dystrophy (DMD) is accompanied by cognitive deficits and psychiatric symptoms. In the brain, dystrophin, the protein responsible for DMD, is localized to a subset of GABAergic synapses, but its role in brain function has not fully been addressed. Here, we report that defensive behaviour, a response to danger or a threat, is enhanced in dystrophin-deficient mdx mice. Mdx mice consistently showed potent defensive freezing responses to a brief restraint that never induced such responses in wild-type mice. Unconditioned and conditioned defensive responses to electrical footshock were also enhanced in mdx mice. No outstanding abnormality was evident in the performances of mdx mice in the elevated plus maze test, suggesting that the anxiety state is not altered in mdx mice. We found that, in mdx mice, dystrophin is expressed in the amygdala, and that, in the basolateral nucleus (BLA), the numbers of GABAA receptor α2 subunit clusters are reduced. In BLA pyramidal neurons, the frequency of norepinephrine-induced GABAergic inhibitory synaptic currents was reduced markedly in mdx mice. Morpholino oligonucleotide-induced expression of truncated dystrophin in the brains of mdx mice, but not in the muscle, ameliorated the abnormal freezing response to restraint. These results suggest that a deficit of brain dystrophin induces an alteration of amygdala local inhibitory neuronal circuits and enhancement of fear-motivated defensive behaviours in mice.

Keywords: GABAergic synapse; scaffolding proteins; dystrophin; defensive behaviour; amygdala

Journal Article.  8308 words.  Illustrated.

Subjects: Neurology ; Neuroscience

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