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.
Highlights
The striatum regulates voluntary movement and reward-related learning by integrating excitatory inputs from the cerebral cortex and thalamus (Alexander et al, 1986; Hikosaka et al, 2000; Kreitzer and Malenka, 2008; Redgrave et al, 2011; Peak et al, 2019)
The present study demonstrated that the rule of cellular correlation between dopamine receptor expression and projection pathways was conserved in the unusual part of the caudal striatum (cStr) where dopamine receptor D1 (D1R)-medium spiny neuron (MSN) and dopamine receptor D2 (D2R)-MSNs are unevenly distributed
We identified the characteristic projections from the poor zones to substantia nigra pars lateralis (SNpl) via the direct pathway and to the caudal globus pallidus (GP) via the indirect pathway (Figures 6, 7 and Supplementary Figures 2–4)
Summary
The striatum regulates voluntary movement and reward-related learning by integrating excitatory inputs from the cerebral cortex and thalamus (Alexander et al, 1986; Hikosaka et al, 2000; Kreitzer and Malenka, 2008; Redgrave et al, 2011; Peak et al, 2019). The medium spiny projection neurons (MSNs)—i.e., the major population of striatal neurons—are classified into two groups: direct and indirect pathway neurons, depending on their projection targets and gene expression. The direct pathway MSNs (dMSNs) directly transmit information to output nuclei, such as the globus pallidus internal segment (GPi) [the counter part of the entopeduncular nucleus (EP) in rodents] and substantia nigra (SN). The dMSNs express gamma-aminobutyric acid (GABA), dopamine receptor D1 (D1R), and substance P. Indirect pathway MSNs (iMSNs) express GABA, dopamine receptor D2 (D2R), and enkephalin, and project to the globus pallidus external segment (GP in rodents). GP projects to the output nuclei, namely, iMSNs indirectly project to the output nuclei (Albin et al, 1989; Alexander and Crutcher, 1990; Graybiel, 1990). It has long been believed that both types of projection neurons are randomly distributed (Lança et al, 1986; Gerfen, 1989; Tinterri et al, 2018) and each local striatal area contains an almost equal proportion of both types (Selemon and Goldman-Rakic, 1990; Hedreen and DeLong, 1991)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
