Conservation of the direct and indirect pathways dichotomy in mouse caudal striatum with uneven distribution of dopamine receptor D1- and D2-expressing neurons

The striatum is one of the key nuclei for adequate control of voluntary behaviors and reinforcement learning. Two striatal projection neuron types, expressing either dopamine receptor D1 (D1R) or dopamine receptor D2 (D2R) constitute two independent output routes: the direct or indirect pathways, respectively. These pathways co-work in balance to achieve coordinated behavior. Two projection neuron types are equivalently intermingled in most striatal space. However, recent studies revealed two atypical zones in the caudal striatum: the zone in which D1R-neurons are the minor population (D1R-poor zone) and that in which D2R-neurons are the minority (D2R-poor zone). It remains obscure as to whether these imbalanced zones have similar properties on axonal projections and electrophysiology to other striatal regions. Based on morphological experiments in mice using immunofluorescence, in situ hybridization, and neural tracing, here, we revealed the poor zones densely projected to the globus pallidus and substantia nigra pars lateralis, with a few collaterals in substantia nigra pars reticulata and compacta. As other striatal regions, D1R-neurons were the direct pathway neurons, while projection neurons in the poor zones possessed similar electrophysiological membrane properties to those in the conventional striatum using in vitro electrophysiological recording. In addition, the poor zones existed irrespective of the age of mice. We also identified the poor zones in the common marmoset as well as other rodents. These results suggest that the poor zones in the caudal striatum follow the conventional projection patterns irrespective of imbalanced distribution of projection neurons. The poor zones could be an innate structure and common in mammals and relate to specific functions via highly restricted projections.