Striatonigrostriatal Circuit Architecture for Disinhibition of Dopamine Signaling

SUMMARY/ABSTRACTThe basal ganglia operate largely in closed parallel loops, including an associative circuit for goal-directed behavior originating from the dorsomedial striatum (DMS) and a somatosensory circuit important for habit formation originating from the dorsolateral striatum (DLS). An exception to this parallel circuit organization has been proposed to explain how information might be transferred between striatal subregions, for example from DMS to DLS during habit formation. The "ascending spiral hypothesis" proposes that DMS disinhibits dopamine signaling in DLS through a tri-synaptic, open-loop striato-nigro-striatal circuit. Here, we used transsynaptic and intersectional genetic tools to investigate both closed- and open-loop striato-nigro-striatal circuits. We found strong evidence for closed loops, which would allow striatal subregions to regulate their own dopamine release. We also found evidence for functional synapses in open loops. However, these synapses were unable to modulate tonic dopamine neuron firing, questioning the prominence of their role in mediating crosstalk between striatal subregions.