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

• Published in: Cerebral cortex (New York, N.Y. 1991) Vol. 18; no. 2; pp. 315 - 330
• Main Authors: Uematsu, Masakazu, Hirai, Yasuharu, Karube, Fuyuki, Ebihara, Satoe, Kato, Megumi, Abe, Kuniya, Obata, Kunihiko, Yoshida, Sachiko, Hirabayashi, Masumi, Yanagawa, Yuchio, Kawaguchi, Yasuo
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01-02-2008; Oxford Publishing Limited (England)
• Subjects: Animals; Animals, Genetically Modified; bacterial artificial chromosome; Bacterial Proteins; Brain Mapping - methods; Cerebral Cortex - metabolism; cortex; gamma-Aminobutyric Acid - metabolism; interneuron; Interneurons - metabolism; Luminescent Proteins; Microscopy, Fluorescence - methods; Neural Inhibition - physiology; Rats - genetics; Synaptic Transmission - physiology; Tissue Distribution; transgenic rat; Venus; vesicular GABA transporter; bacterial artificial chromosome; cortex; transgenic rat; interneuron; vesicular GABA transporter; Venus
• ISSN: 1047-3211; 1460-2199
• DOI: 10.1093/cercor/bhm056

Although neocortical GABAergic (γ-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 α-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.