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

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.

Subthalamic nucleus exclusively evokes dopamine release in the tail of the striatum

“…Several possible reasons could explain all these differences between the tail and dorsolateral striatum. Firstly, expression of tyrosine hydroxylase is lower in the tail striatum (Miyamoto et al, 2019; Ogata et al, 2022). This finding, albeit in mouse, could be explained by a comparatively lower density of dopamine terminals in the tail striatum, which would lead to less spontaneous dopamine release and subsequent lower basal concentration (Liu et al, 2021; Rice et al, 2011) as well as smaller evoked dopamine release.…”

“…Indeed, unlike the dorsolateral striatum which receives input from densely packed dopamine neurons in the SNc that branch extensively (Matsuda et al, 2009), the tail striatum is innervated by a more sparsely populated cluster of dopamine neurons in the SNL (Fu et al, 2012; González‐Hernández & Rodríguez, 2000). Furthermore, unlike the relatively homogenous dorsolateral striatum, studies have shown that the tail striatum comprises of multiple subdivisions, notably two broad ventral regions lacking either the D 1 or D 2 dopamine receptors (Gangarossa et al, 2013; Miyamoto et al, 2019; Ogata et al, 2022). These subdivisions also have different compositions of GABAergic and cholinergic interneurons, which, through cortico‐striatal input, can modulate basal dopamine (Abudukeyoumu et al, 2019; Lopes et al, 2019; Roberts et al, 2021).…”

Dopamine transmission in the tail striatum: Regional variation and contribution of dopamine clearance mechanisms

“…Little is known about this division that could explain the disparity between TH expression and reduced dopamine release, largely because of its notable absence in previous tail striatum studies (e.g. Ogata et al., 2022). This discrepancy suggests additional local mechanisms modulating dopamine release are present in the dorsal tail striatum, but it remains to be seen what these are precisely.…”

“…Peak dopamine clearance velocity was also similar between most regions but was uniquely low in the intermediate division. We propose that this is as a result of the particularly low expression of DAT in this region (Ogata et al, 2022)…”

Dystonia-like behaviors and impaired sensory–motor integration following neurotoxic lesion of the pedunculopontine tegmental nucleus in mice

“…A PPTg lesion was thought to induce the hypoactivity of the STN and SNpr, and it was confirmed that a unilateral lesion of the PPTg could reverse the hyperactivity of the STN and SNpr in a 6-hydroxydopamine rat model ( 57 ). Moreover, a recent neuroanatomical study showed that the lateral part of the SNpr mainly received indirect pathway-related innervations ( 58 ). Combined with our finding that the neural activity of the lateral part of the SNpr was significantly reduced, it was proposed that the indirect pathway was impaired.…”