Striatal Control of Movement: A Role for New Neuronal (Sub-) Populations?

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.

Presynaptic cGMP sets synaptic strength in the striatum and is important for motor learning

“…M1 and PF are the two main sources of glutamatergic innervation to the striatum and EPSCs from both inputs increased equally after inhibition of PDEs (Fig 1D–F ). Striatal SPNs further divide into two major populations, forming the so‐called direct and indirect pathways (dSPNs and iSPNs, respectively), which have distinct transcriptional, molecular, electrophysiological, and morphological characteristics (Gertler et al , 2008 ; Heiman et al , 2008 ; Planert et al , 2013 ; Fieblinger et al , 2014 ; Gokce et al , 2016 ; Saunders et al , 2018 ; Fieblinger, 2021 ). Using viral transduction in a transgenic mouse that expresses Cre‐recombinase selectively in iSPNs (BAC‐ adora2a ‐Cre), Cre‐positive iSPNs were labeled with GFP and Cre‐negative neurons with tdTomato (Fig 1G ).…”

Integrative multi-dimensional characterization of striatal projection neuron heterogeneity in adult brain

“…The convergence between spatial mapping and multi-omics also supports a simplified classification of SPN cell types defined by their expression of DA receptors (D1R-only, D2R-only, D1/2R, D1/3R) and anatomic localization. Indeed, canonical D1R-only and D2R-only expressing cell types are known to have striosome and matrix subtypes [107][108][109][110][111] . Our combined multi-dimensional data defined the D1-NUDAP subtypes as D1/2R co-expressing eSPNs clustered within the OT 48 .…”

Neuro- and Cardiovascular Activities of Montivipera bornmuelleri Snake Venom

“…P19-derived neuronal cultures also express the dopamine D2 receptor, a molecular characteristic of striatopallidal medium spiny neurons (MSNs) [ 30 ]. MSNs represent 95% of the neuronal population in the striatum [ 48 ], a critical hub for locomotion control [ 49 ]. The high toxicity of the venom on this neuronal model could therefore suggest the observed motor behavior defects in a recently reported case of M. bornmuelleri snake bite [ 50 ].…”