Whole-Brain Mapping of Direct Inputs to Midbrain Dopamine Neurons

Recent studies indicate that dopamine neurons in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) convey distinct signals. To explore this difference, we comprehensively identified each area's monosynaptic inputs using the rabies virus. We show that dopamine neurons in both areas integrate inputs from a more diverse collection of areas than previously thought, including autonomic, motor, and somatosensory areas. SNc and VTA dopamine neurons receive contrasting excitatory inputs: the former from the somatosensory/motor cortex and subthalamic nucleus, which may explain their short-latency responses to salient events; and the latter from the lateral hypothalamus, which may explain their involvement in value coding. We demonstrate that neurons in the striatum that project directly to dopamine neurons form patches in both the dorsal and ventral striatum, whereas those projecting to GABAergic neurons are distributed in the matrix compartment. Neuron-type-specific connectivity lays a foundation for studying how dopamine neurons compute outputs. ► Tracing direct inputs to midbrain dopamine (DA) neurons using rabies virus ► DA neurons receive direct inputs from autonomic, motor and somatosensory areas ► Direct cortical and subthalamic inputs may explain short-latency excitation of SNc ► The largest numbers of direct inputs come from dorsal and ventral striatum patches Understanding how the activity of a given type of neuron is regulated requires understanding their inputs. Watabe-Uchida et al. applied a rabies-virus-mediated tracing method to midbrain dopamine neurons to provide a comprehensive view of their inputs.