title: Diversity of transgenic mouse models for selective targeting of midbrain dopamine neurons.
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.
authors.affiliation: 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.
authors.forename: Stephan
authors.initials: S
authors.lastname: Lammel
authors.affiliation: Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 265 Campus Drive, Stanford CA 94305-5453, USA.
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Steinberg
authors.affiliation: 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.
authors.forename: Csaba
authors.initials: C
authors.lastname: Földy
authors.affiliation: Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 265 Campus Drive, Stanford CA 94305-5453, USA.
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Wall
authors.affiliation: 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.
authors.forename: Kevin
authors.initials: K
authors.lastname: Beier
authors.affiliation: Howard Hughes Medical Institute and Department of Biology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Liqun
authors.initials: L
authors.lastname: Luo
authors.affiliation: 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.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Malenka
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000378:metabolism*; D059330:GABAergic Neurons / Q000378:metabolism*; D015870:Gene Expression; D019262:Habenula / Q000378:metabolism*; D008636:Mesencephalon / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics* / Q000378:metabolism; D023421:Models, Animal; D011401:Promoter Regions, Genetic; D015533:Transcriptional Activation; D017557:Ventral Tegmental Area / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D005680:gamma-Aminobutyric Acid; D004298:Dopamine