Cell
Volume 162, Issue 3, 30 July 2015, Pages 622-634
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Article
Circuit Architecture of VTA Dopamine Neurons Revealed by Systematic Input-Output Mapping

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Highlights

  • VTA dopamine (DA) and GABA neurons receive similar inputs from diverse sources

  • VTA-DA neurons projecting to different output sites receive biased input

  • VTA-DA neurons projecting to lateral and medial NAc innervate non-overlapping targets

  • A top-down anterior cortex→VTA-DA→lateral NAc circuit is reinforcing

Summary

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.

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5

Present address: Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan

6

Present address: Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA