Afferent Inputs to Neurotransmitter-Defined Cell Types in the Ventral Tegmental Area

• Published in: Cell reports (Cambridge) 2016-06, Vol.15 (12), p.2796-2808
• Main Authors: Faget, Lauren, Osakada, Fumitaka, Duan, Jinyi, Ressler, Reed, Johnson, Alexander B., Proudfoot, James A., Yoo, Ji Hoon, Callaway, Edward M., Hnasko, Thomas S.
• Format: Article
• Language: English
• Subjects: Animals; Cell Count; Female; Immunohistochemistry; Male; Mice; Neurons, Afferent - metabolism; Neurotransmitter Agents - metabolism; Rabies virus - physiology; Synapses - metabolism; Ventral Tegmental Area - cytology; Ventral Tegmental Area - metabolism
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2016.05.057

The ventral tegmental area (VTA) plays a central role in the neural circuit control of behavioral reinforcement. Though considered a dopaminergic nucleus, the VTA contains substantial heterogeneity in neurotransmitter type, containing also GABA and glutamate neurons. Here, we used a combinatorial viral approach to transsynaptically label afferents to defined VTA dopamine, GABA, or glutamate neurons. Surprisingly, we find that these populations received qualitatively similar inputs, with dominant and comparable projections from the lateral hypothalamus, raphe, and ventral pallidum. However, notable differences were observed, with striatal regions and globus pallidus providing a greater share of input to VTA dopamine neurons, cortical input preferentially on to glutamate neurons, and GABA neurons receiving proportionally more input from the lateral habenula and laterodorsal tegmental nucleus. By comparing inputs to each of the transmitter-defined VTA cell types, this study sheds important light on the systems-level organization of diverse inputs to VTA. [Display omitted] •Dopamine, GABA, and glutamate VTA neurons receive qualitatively similar inputs•Hypothalamus and raphe provide the largest inputs to each VTA cell type•Dopamine neurons receive proportionally more input from basal ganglia•Glutamate neurons receive more cortical inputs Afferents to ventral tegmental area (VTA) neurons control reward-seeking behaviors, but their relative arrangement onto heterogeneous VTA cell types has remained largely unknown. Faget et al. now use an optimized transsynaptic retrograde tracing approach to provide a comprehensive map of inputs to each transmitter-defined VTA cell type.