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Neuron. 2015 Jan 21;85(2):429-38. doi: 10.1016/j.neuron.2014.12.036.

Diversity of transgenic mouse models for selective targeting of midbrain dopamine neurons.

Author information

1
Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 265 Campus Drive, Stanford CA 94305-5453, USA. Electronic address: lammel@berkeley.edu.
2
Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 265 Campus Drive, Stanford CA 94305-5453, USA.
3
Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 265 Campus Drive, Stanford CA 94305-5453, USA; Department of Molecular and Cellular Physiology, Stanford University School of Medicine, 265 Campus Drive, Stanford CA 94305-5453, USA.
4
Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 265 Campus Drive, Stanford CA 94305-5453, USA; Howard Hughes Medical Institute and Department of Biology, Stanford University, Stanford, CA 94305, USA.
5
Howard Hughes Medical Institute and Department of Biology, Stanford University, Stanford, CA 94305, USA.
6
Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 265 Campus Drive, Stanford CA 94305-5453, USA. Electronic address: malenka@stanford.edu.

Abstract

Ventral tegmental area (VTA) dopamine (DA) neurons have been implicated in reward, aversion, salience, cognition, and several neuropsychiatric disorders. Optogenetic approaches involving transgenic Cre-driver mouse lines provide powerful tools for dissecting DA-specific functions. However, the emerging complexity of VTA circuits requires Cre-driver mouse lines that restrict transgene expression to a precisely defined cell population. Because of recent work reporting that VTA DA neurons projecting to the lateral habenula release GABA, but not DA, we performed an extensive anatomical, molecular, and functional characterization of prominent DA transgenic mouse driver lines. We find that transgenes under control of the tyrosine hydroxylase, but not the dopamine transporter, promoter exhibit dramatic non-DA cell-specific expression patterns within and around VTA nuclei. Our results demonstrate how Cre expression in unintentionally targeted cells in transgenic mouse lines can confound the interpretation of supposedly cell-type-specific experiments. This Matters Arising paper is in response to Stamatakis et al. (2013), published in Neuron. See also the Matters Arising Response paper by Stuber et al. (2015), published concurrently with this Matters Arising in Neuron.

PMID:
25611513
PMCID:
PMC5037114
DOI:
10.1016/j.neuron.2014.12.036
[Indexed for MEDLINE]
Free PMC Article

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