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

Cereb Cortex. 2008 Feb;18(2):315-30. doi: 10.1093/cercor/bhm056. Epub 2007 May 20.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Bacterial Proteins*
  • Brain Mapping / methods*
  • Cerebral Cortex / metabolism*
  • Interneurons / metabolism*
  • Luminescent Proteins*
  • Microscopy, Fluorescence / methods
  • Neural Inhibition / physiology*
  • Rats / genetics
  • Synaptic Transmission / physiology*
  • Tissue Distribution
  • gamma-Aminobutyric Acid / metabolism*

Substances

  • Bacterial Proteins
  • Luminescent Proteins
  • yellow fluorescent protein, Bacteria
  • gamma-Aminobutyric Acid