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@ARTICLE{MllerKomorowska:151549,
author = {Müller-Komorowska, Daniel and Opitz, Thoralf and
Elzoheiry, Shehabeldin and Schweizer, Michaela and Ambrad
Giovannetti, Eleonora and Beck, Heinz},
title = {{N}onspecific {E}xpression in {L}imited {E}xcitatory {C}ell
{P}opulations in {I}nterneuron-{T}argeting {C}re-driver
{L}ines {C}an {H}ave {L}arge {F}unctional {E}ffects},
journal = {Frontiers in neural circuits},
volume = {14},
issn = {1662-5110},
address = {Lausanne},
publisher = {Frontiers Research Foundation},
reportid = {DZNE-2020-01133},
pages = {16},
year = {2020},
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.},
keywords = {Animals / CA3 Region, Hippocampal: chemistry / CA3 Region,
Hippocampal: cytology / CA3 Region, Hippocampal: metabolism
/ Gene Expression / Integrases: analysis / Integrases:
biosynthesis / Integrases: genetics / Interneurons:
chemistry / Interneurons: metabolism / Mice / Mice, Inbred
C57BL / Mice, Transgenic / Optogenetics: methods /
Somatostatin: analysis / Somatostatin: biosynthesis /
Somatostatin: genetics},
cin = {U Preclinical Researchers - Bonn},
ddc = {610},
cid = {I:(DE-2719)7000005},
pnm = {342 - Disease Mechanisms and Model Systems (POF3-342)},
pid = {G:(DE-HGF)POF3-342},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:32395103},
pmc = {pmc:PMC7197702},
doi = {10.3389/fncir.2020.00016},
url = {https://pub.dzne.de/record/151549},
}