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.
Circuit Architecture of VTA Dopamine Neurons Revealed by Systematic Input-Output Mapping
Beier, K. T.; Steinberg, E. E.; DeLoach, K. E.; Xie, S.; Miyamichi, K.; Schwarz, L.; Gao, X. J.; Kremer, E. J.; Malenka, R. C.; Luo, L.
2015-07-30 / vol 162 / pages 622-34
10.1016/j.cell.2015.07.015 S0092-8674(15)00852-1 [pii]
1097-4172 (Electronic) 0092-8674 (Linking)
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