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Cell. 2015 Jul 30;162(3):622-34. doi: 10.1016/j.cell.2015.07.015.

Circuit Architecture of VTA Dopamine Neurons Revealed by Systematic Input-Output Mapping.

Author information

1
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.
2
Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
3
Howard Hughes Medical Institute and Department of Biology, Stanford University, Stanford, CA 94305, USA.
4
Institut de Génétique Moléculaire de Montpellier, CNRS 5535, 34293 Montpellier, France; Université de Montpellier, 34000 Montpellier, France.
5
Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: malenka@stanford.edu.
6
Howard Hughes Medical Institute and Department of Biology, Stanford University, Stanford, CA 94305, USA. Electronic address: lluo@stanford.edu.

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.

PMID:
26232228
PMCID:
PMC4522312
DOI:
10.1016/j.cell.2015.07.015
[Indexed for MEDLINE]
Free PMC Article

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