Nonspecific Expression in Limited Excitatory Cell Populations in Interneuron-Targeting Cre-driver Lines Can Have Large Functional Effects
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Nonspecific Expression in Limited Excitatory Cell Populations in Interneuron-Targeting Cre-driver Lines Can Have Large Functional Effects. / Müller-Komorowska, Daniel; Opitz, Thoralf; Elzoheiry, Shehabeldin; Schweizer, Michaela; Ambrad Giovannetti, Eleonora; Beck, Heinz.
in: FRONT NEURAL CIRCUIT, Jahrgang 14, 27.04.2020, S. 16.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Nonspecific Expression in Limited Excitatory Cell Populations in Interneuron-Targeting Cre-driver Lines Can Have Large Functional Effects
AU - Müller-Komorowska, Daniel
AU - Opitz, Thoralf
AU - Elzoheiry, Shehabeldin
AU - Schweizer, Michaela
AU - Ambrad Giovannetti, Eleonora
AU - Beck, Heinz
N1 - Copyright © 2020 Müller-Komorowska, Opitz, Elzoheiry, Schweizer, Ambrad Giovannetti and Beck.
PY - 2020/4/27
Y1 - 2020/4/27
N2 - 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.
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.
U2 - 10.3389/fncir.2020.00016
DO - 10.3389/fncir.2020.00016
M3 - SCORING: Journal article
C2 - 32395103
VL - 14
SP - 16
JO - FRONT NEURAL CIRCUIT
JF - FRONT NEURAL CIRCUIT
SN - 1662-5110
ER -
