title: Circuit Architecture of VTA Dopamine Neurons Revealed by Systematic Input-Output Mapping.
abstract: Dopamine (DA) neurons in the midbrain ventral tegmental area (VTA) integrate complex inputs to encode multiple signals that influence motivated behaviors via diverse projections. Here, we combine axon-initiated viral transduction with rabies-mediated trans-synaptic tracing and Cre-based cell-type-specific targeting to systematically map input-output relationships of VTA-DA neurons. We found that VTA-DA (and VTA-GABA) neurons receive excitatory, inhibitory, and modulatory input from diverse sources. VTA-DA neurons projecting to different forebrain regions exhibit specific biases in their input selection. VTA-DA neurons projecting to lateral and medial nucleus accumbens innervate largely non-overlapping striatal targets, with the latter also sending extensive extra-striatal axon collaterals. Using electrophysiology and behavior, we validated new circuits identified in our tracing studies, including a previously unappreciated top-down reinforcing circuit from anterior cortex to lateral nucleus accumbens via VTA-DA neurons. This study highlights the utility of our viral-genetic tracing strategies to elucidate the complex neural substrates that underlie motivated behaviors.
authors.affiliation: Howard Hughes Medical Institute and Department of Biology, Stanford University, Stanford, CA 94305, USA; Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Kevin T
authors.initials: KT
authors.lastname: Beier
authors.affiliation: Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Steinberg
authors.affiliation: Howard Hughes Medical Institute and Department of Biology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Katherine E
authors.initials: KE
authors.lastname: DeLoach
authors.affiliation: Howard Hughes Medical Institute and Department of Biology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Stanley
authors.initials: S
authors.lastname: Xie
authors.affiliation: Howard Hughes Medical Institute and Department of Biology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Miyamichi
authors.affiliation: Howard Hughes Medical Institute and Department of Biology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Schwarz
authors.affiliation: Howard Hughes Medical Institute and Department of Biology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Xiaojing J
authors.initials: XJ
authors.lastname: Gao
authors.affiliation: Institut de Génétique Moléculaire de Montpellier, CNRS 5535, 34293 Montpellier, France; Université de Montpellier, 34000 Montpellier, France.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Kremer
authors.affiliation: Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: malenka@stanford.edu.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Malenka
authors.affiliation: Howard Hughes Medical Institute and Department of Biology, Stanford University, Stanford, CA 94305, USA. Electronic address: lluo@stanford.edu.
authors.forename: Liqun
authors.initials: L
authors.lastname: Luo
mesh_terms: D000818:Animals; D001931:Brain Mapping; D004298:Dopamine / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009434:Neural Pathways; D009474:Neurons / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000378:metabolism; D011820:Rabies virus; D017557:Ventral Tegmental Area / Q000166:cytology* / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D005680:gamma-Aminobutyric Acid; D004298:Dopamine