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Cerebral Cortex Advance Access originally published online on May 20, 2007
Cerebral Cortex 2008 18(2):315-330; doi:10.1093/cercor/bhm056
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© The Author 2007. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Quantitative Chemical Composition of Cortical GABAergic Neurons Revealed in Transgenic Venus-Expressing Rats

Masakazu Uematsu1,2,3, Yasuharu Hirai4,5, Fuyuki Karube4, Satoe Ebihara1, Megumi Kato6, Kuniya Abe7, Kunihiko Obata1,8, Sachiko Yoshida2, Masumi Hirabayashi5,6, Yuchio Yanagawa1,3,9 and Yasuo Kawaguchi4,5

1 Laboratory of Neurochemistry, National Institute for Physiological Sciences (NIPS), Okazaki 444-8585, Japan, 2 Department of Materials Science, Toyohashi University of Technology, Toyohashi 441-8580, Japan, 3 SORST, JST, Kawaguchi 332-0012, Japan, 4 Division of Cerebral Circuitry, NIPS, 5 Department of Physiological Sciences, The Graduate University for Advanced Studies (SOKENDAI), Okazaki 444-8585, Japan, 6 Center for Genetic Analysis of Behavior, NIPS, 7 BioResource Center, RIKEN Tsukuba Institute, Tsukuba 305-0074, Japan, 8 Neuronal Circuit Mechanisms Research Group, BSI, RIKEN, Wako 351-0198, Japan, 9 Department of Genetic and Behavioral Neuroscience, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan

Address correspondence to Yasuo Kawaguchi, Division of Cerebral Circuitry, National Institute for Physiological Sciences, Myodaiji, Okazaki 444-8585, Japan. Email: yasuo{at}nips.ac.jp, or to Yuchio Yanagawa, Department of Genetic and Behavioral Neuroscience, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan. Email: yanagawa{at}med.gunma-u.ac.jp.

Although neocortical GABAergic ({gamma}-aminobutyric acidergic) interneurons have been the focus of intense study, especially in the rat, a consensus view of the functional diversity and organization of inhibitory cortical neurons has not yet been achieved. To better analyze GABAergic neurons in the rat, we used a bacterial artificial chromosome (BAC) construct and established 2 lines of transgenic rats that coexpress Venus, a yellow fluorescent protein, with the vesicular GABA transporter. The brain GABA content from both transgenic lines was similar to the level found in wild-type rats. In the frontal cortex, Venus was expressed in >95% of GABAergic neurons, most of which also expressed at least one of 6 biochemical markers, including {alpha}-actitin-2, which preferentially labeled late-spiking neurogliaform cells. Taking advantage of the fact that Venus expression allows for targeted recording from all classes of nonpyramidal cells, irrespective of their somatic morphologies, we demonstrated that fast-spiking neurons, which were heterogeneous in somatic size as well as vertical dendritic projection, had relatively uniform horizontal dimensions, suggesting a cell type–specific columnar input territory. Our data demonstrate the benefits of VGAT-Venus rats for investigating GABAergic circuits, as well as the feasibility of using BAC technology in rats to label subsets of specific, genetically defined neurons.

Key Words: bacterial artificial chromosome • cortex • interneuron • transgenic rat • Venus • vesicular GABA transporter


The first 2 authors contributed equally to this work.


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