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

By Kevin T. Beier, Elizabeth E Steinberg, K. DeLoach, Stanley Xie, Kazunari Miyamichi, L. Schwarz, Xiaojing J. Gao, E. Kremer, R. Malenka, Liqun Luo. 2015

946 citations recorded by the source corpus.

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 transsynaptic 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 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.

Subfields: Cellular and Molecular Neuroscience, Cognitive Neuroscience, Molecular Biology

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cellular and Molecular Neuroscience

1. R. Malenka
2. Karl Deisseroth
3. Liqun Luo
4. T. J. Davidson
5. György Buzsáki
6. Mark T. Harnett
7. Gina G. Turrigiano
8. S. Hyman

In Cognitive Neuroscience

1. R. Malenka
2. Karl Deisseroth
3. T. J. Davidson
4. Liqun Luo
5. György Buzsáki
6. S. Lammel
7. S. Hyman
8. Mark T. Harnett

In Molecular Biology

1. Liqun Luo
2. Karl Deisseroth
3. R. Malenka
4. Mark T. Harnett

Citations in the corpus

• Coordinated and Compartmentalized Neuromodulation Shapes Sensory Processing in Drosophila (2015, neutral): “…important mediators of flexible circuit processing, their anatomic and functional heterogeneity and the intricate wiring of their target neuropils (Beier et al., 2015; Fiorillo et al., 2013; Lammel et al., 2014; Lerner et al., 2015) have made it difficult to resolve how they can selectively alter…”
• Intact-Brain Analyses Reveal Distinct Information Carried by SNc Dopamine Subcircuits (2015, methodology): “Afferents to projection-defined SNc DA neurons also differ; in particular, we here identify new principles of afferent-projection complexity in SNc subcircuits (see Beier et al., 2015 for additional illuminating information regarding VTA subcircuits).”