Abstract
The striatum is a very heterogenous brain area, composed of different domains and compartments, albeit lacking visible anatomical demarcations. Two populations of striatal spiny projection neurons (SPNs) build the so-called direct and indirect pathway of the basal ganglia, whose coordinated activity is essential to control locomotion. Dysfunction of striatal SPNs is part of many movement disorders, such as Parkinson’s disease (PD) and L-DOPA-induced dyskinesia. In this mini review article, I will highlight recent studies utilizing single-cell RNA sequencing to investigate the transcriptional profiles of striatal neurons. These studies discover that SPNs carry a transcriptional signature, indicating both their anatomical location and compartmental identity. Furthermore, the transcriptional profiles reveal the existence of additional distinct neuronal populations and previously unknown SPN sub-populations. In a parallel development, studies in rodent models of PD and L-DOPA-induced dyskinesia (LID) report that direct pathway SPNs do not react uniformly to L-DOPA therapy, and that only a subset of these neurons is underlying the development of abnormal movements. Together, these studies demonstrate a new level of cellular complexity for striatal (dys-) function and locomotor control.
Highlights
The striatum is an evolutionarily conserved brain area and input structure to the basal ganglia (Grillner et al, 2013)
Lesion or loss-of-function of the direct pathway reduces locomotion in animals, whereas disabling the indirect pathway results in hyperlocomotion (Durieux et al, 2009, 2012; Bateup et al, 2010). This is corroborated by optogenetic studies, showing that overt activation of the direct pathway induces locomotion, and activation of the indirect pathway leads to a cessation of ongoing movement (Kravitz et al, 2010)
The ‘‘box-and-arrow’’ model has been instrumental to a better understanding of the network changes underlying movement disorders and locomotor dysfunction; it has become apparent that the model does not reflect the true complexity of the basal ganglia network (Calabresi et al, 2014; Plotkin and Goldberg, 2019)
Summary
Dysfunction of striatal SPNs is part of many movement disorders, such as Parkinson’s disease (PD) and L-DOPA-induced dyskinesia In this mini review article, I will highlight recent studies utilizing single-cell RNA sequencing to investigate the transcriptional profiles of striatal neurons. Studies in rodent models of PD and L-DOPA-induced dyskinesia (LID) report that direct pathway SPNs do not react uniformly to L-DOPA therapy, and that only a subset of these neurons is underlying the development of abnormal movements. Together, these studies demonstrate a new level of cellular complexity for striatal (dys-) function and locomotor control
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