Journal Article

DZNE-2020-01133

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Nonspecific Expression in Limited Excitatory Cell Populations in Interneuron-Targeting Cre-driver Lines Can Have Large Functional Effects

Müller-Komorowska, D. ; Opitz, T. ; Elzoheiry, S. ; Schweizer, M. ; Ambrad Giovannetti, E.DZNE* ; Beck, H. (Corresponding author)

2020
Frontiers Research Foundation Lausanne

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Please use a persistent id in citations: doi:10.3389/fncir.2020.00016

Abstract: Transgenic Cre-recombinase expressing mouse lines are widely used to express fluorescent proteins and opto-/chemogenetic actuators, making them a cornerstone of modern neuroscience. The investigation of interneurons in particular has benefitted from the ability to genetically target specific cell types. However, the specificity of some Cre driver lines has been called into question. Here, we show that nonspecific expression in a subset of hippocampal neurons can have substantial nonspecific functional effects in a somatostatin-Cre (SST-Cre) mouse line. Nonspecific targeting of CA3 pyramidal cells caused large optogenetically evoked excitatory currents in remote brain regions. Similar, but less severe patterns of nonspecific expression were observed in a widely used SST-IRES-Cre line, when crossed with a reporter mouse line. Viral transduction on the other hand yielded more specific expression but still resulted in nonspecific expression in a minority of pyramidal layer cells. These results suggest that a careful analysis of specificity is mandatory before the use of Cre driver lines for opto- or chemogenetic manipulation approaches.

Keyword(s): Animals (MeSH) ; CA3 Region, Hippocampal: chemistry (MeSH) ; CA3 Region, Hippocampal: cytology (MeSH) ; CA3 Region, Hippocampal: metabolism (MeSH) ; Gene Expression (MeSH) ; Integrases: analysis (MeSH) ; Integrases: biosynthesis (MeSH) ; Integrases: genetics (MeSH) ; Interneurons: chemistry (MeSH) ; Interneurons: metabolism (MeSH) ; Mice (MeSH) ; Mice, Inbred C57BL (MeSH) ; Mice, Transgenic (MeSH) ; Optogenetics: methods (MeSH) ; Somatostatin: analysis (MeSH) ; Somatostatin: biosynthesis (MeSH) ; Somatostatin: genetics (MeSH)

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Contributing Institute(s):

1. U Preclinical Researchers - Bonn (U Preclinical Researchers - Bonn)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Appears in the scientific report 2020

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Database coverage:
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