TY  - JOUR
AU  - Müller-Komorowska, Daniel
AU  - Opitz, Thoralf
AU  - Elzoheiry, Shehabeldin
AU  - Schweizer, Michaela
AU  - Ambrad Giovannetti, Eleonora
AU  - Beck, Heinz
TI  - Nonspecific Expression in Limited Excitatory Cell Populations in Interneuron-Targeting Cre-driver Lines Can Have Large Functional Effects
JO  - Frontiers in neural circuits
VL  - 14
SN  - 1662-5110
CY  - Lausanne
PB  - Frontiers Research Foundation
M1  - DZNE-2020-01133
SP  - 16
PY  - 2020
AB  - 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.
KW  - Animals
KW  - CA3 Region, Hippocampal: chemistry
KW  - CA3 Region, Hippocampal: cytology
KW  - CA3 Region, Hippocampal: metabolism
KW  - Gene Expression
KW  - Integrases: analysis
KW  - Integrases: biosynthesis
KW  - Integrases: genetics
KW  - Interneurons: chemistry
KW  - Interneurons: metabolism
KW  - Mice
KW  - Mice, Inbred C57BL
KW  - Mice, Transgenic
KW  - Optogenetics: methods
KW  - Somatostatin: analysis
KW  - Somatostatin: biosynthesis
KW  - Somatostatin: genetics
LB  - PUB:(DE-HGF)16
C6  - pmid:32395103
C2  - pmc:PMC7197702
DO  - DOI:10.3389/fncir.2020.00016
UR  - https://pub.dzne.de/record/151549
ER  -