Motor-to-Limbic Design of Direct Synaptic Communication between Dopamine Neurons in the Midbrain.

Midbrain dopamine (DA) neurons are diverse with distinct subpopulations being essential for key functions of the brain: nigrostriatal DA neurons for voluntary movement and mesolimbic DA neurons for learning from reward prediction errors. In addition to being primarily associated with distinct senso-motor or limbic cortical-striatal circuits, DA subpopulations also directly communicate with each other via local DA release in the midbrain. While the inhibitory synaptic nature of this dopamine-to-dopamine signaling has been well established, the pre- and postsynaptic identity and logic of connectivity among DA subpopulations are still unresolved. To fill this gap, we combined retrograde tracing with projection-specific optogenetic stimulation of DA neurons and patch-clamp recordings in vitro in the adult mouse of either sex. We functionally identified a unidirectional, motor-to-limbic design of the DA synapse in the midbrain. This motor-to-limbic negative feedback connection in the midbrain was independently confirmed by monosynaptic rabies tracing of projection-defined DA subpopulations. This DA synapse might complement the limbic-to-motor striato-nigro-striatal feedforward architecture of the basal ganglia.