Conservation of the Direct and Indirect Pathway Dichotomy in Mouse Caudal Striatum With Uneven Distribution of Dopamine Receptor D1- and D2-Expressing Neurons

Kumiko Ogata; Fuko Kadono; Yasuharu Hirai; Ken-Ichi Inoue; Masahiko Takada; Fuyuki Karube; Fumino Fujiyama

doi:10.3389/fnana.2022.809446

Conservation of the Direct and Indirect Pathway Dichotomy in Mouse Caudal Striatum With Uneven Distribution of Dopamine Receptor D1- and D2-Expressing Neurons

Front Neuroanat. 2022 Feb 4:16:809446. doi: 10.3389/fnana.2022.809446. eCollection 2022.

Authors

Kumiko Ogata¹, Fuko Kadono², Yasuharu Hirai^{1

2}, Ken-Ichi Inoue³, Masahiko Takada³, Fuyuki Karube^{1

2}, Fumino Fujiyama^{1

2}

Affiliations

¹ Laboratory of Neural Circuitry, Graduate School of Brain Science, Doshisha University, Kyotanabe, Japan.
² Laboratory of Histology and Cytology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
³ Systems Neuroscience Section, Primate Research Institute, Kyoto University, Inuyama, Japan.

Abstract

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 compared to other striatal regions. Based on morphological experiments in mice using immunofluorescence, in situ hybridization, and neural tracing, here, we revealed that 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. Similar to that in other striatal regions, D1R-neurons were the direct pathway neurons. We also showed that the membrane properties of projection neurons in the poor zones were largely similar to those in the conventional striatum using in vitro electrophysiological recording. In addition, the poor zones existed irrespective of the age or sex 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 the imbalanced distribution of projection neurons. The poor zones could be an innate structure and common in mammals. The unique striatal zones possessing highly restricted projections could relate to functions different from those of motor-related striatum.

Keywords: basal ganglia; direct pathway; dopamine receptor; indirect pathway; striatum; substantia nigra pars lateralis; tyrosine hydroxylase.