Virus-mediated swapping of zolpidem-insensitive with zolpidem-sensitive GABAA receptors in cortical pyramidal cells

Sümegi, Máté and Fukazawa, Yugo and Matsui, Ko and Lőrincz, Andrea and Eyre, Mark David and Nusser, Zoltán and Shigemoto, Ryuichi (2012) Virus-mediated swapping of zolpidem-insensitive with zolpidem-sensitive GABAA receptors in cortical pyramidal cells. JOURNAL OF PHYSIOLOGY - LONDON, 590 (7). pp. 1517-1534. ISSN 0022-3751

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Abstract

Key points We generated lenti- and adeno-associated viruses which were used to replace the zolpidem-insensitive GABA(A) receptors of a transgenic mouse line with wild-type, zolpidem-sensitive ones. The virally expressed wild-type, zolpidem-sensitive GABA(A) receptor gamma2 subunits were tagged with a small immunotag (AU1). Light microscopic fluorescent and electron microscopic freeze-fracture immunogold labelling revealed that the virally introduced AU1-tagged gamma2 subunit-containing receptors had a normal synaptic distribution on cortical pyramidal cells. In vitro patch-clamp recordings demonstrated that the insertion of this immunotag did not alter the kinetic and pharmacological properties of the virally inserted gamma2 subunits. Our results demonstrate a novel transgenic-viral pharmacogenetic approach, which allows the selective silencing of well-defined neuronal populations in the brain.

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