Topic: striatal projection neurons

Cell replacement therapy (CRT) holds promise for restoring atrophied tissue in Huntington’s Disease (HD) by replenishing degenerating striatal projection neurons (SPNs). However, the heterogeneous cell compositions resulting from striatal differentiation protocols hinder clinical translation. Standardizing production procedures is essential to ensure the generation of defined and safe cell products. This study aims to devise a novel therapeutic approach for brain tissue regeneration in HD, ensuring the presence of specified SPN progenitors while excluding overly proliferative cell types.Here,

Regenerative medicine aims to revolutionize medical practice by offering cures for severe diseases. This is achieved through the utilization of human pluripotent stem cell (hPSC) lines, which undergo controlled differentiation before being transplanted into patients. A significant challenge lies in developing safe, robust, and controlled differentiation protocols, requiring the adaptation of research-only reagents to good manufacturing practice (GMP) standards.Cell-based therapies for Huntington’s disease aspire to restore neuronal circuitry and function by replacing lost neurons. Here, we pre

Basal ganglia (BG) circuits are crucial for motor initiation and suppression. Dopamine loss in these circuits triggers Parkinson's disease (PD) and debilitating motor impairments such as akinesia and bradykinesia. Levodopa treatments alleviates PD symptoms, but often leads to abnormal involuntary movements known as levodopa-induced dyskinesias (LIDs). Understanding the neuronal mechanism of LIDs is essential for developing novel therapeutic strategies. Recent studies suggest that LIDs result from abnormal striatal activity, yet how this activity affects downstream BG circuits to generate LIDs

Huntington’s disease (HD) is a currently incurable neurodegenerative disorder that manifests itself through motor and cognitive symptoms due to a predominant loss of striatal projection neurons (SPNs) in the striatum. Although HD is a neurodegenerative disease, growing evidence show that developmental alterations could be a key factor in the disease, determining the future vulnerability of certain cell types, such as SPNs. Here we show an early HD-related gene expression pattern elucidated by bulk and single-cell RNA sequencing performed on wt and HD isolated mouse striatal primordia at differ

The basal ganglia are notorious for their influence on action control and modulation of movements. Proper organization of neuronal activity within the two efferent pathways of the dorsal striatum, a major input of basal ganglia, is critical for appropriate behavioral control. The classical model of basal ganglia suggests that striatal indirect and direct pathways exert opposite action on the thalamo-cortical activation triggering motor control. Recent studies challenged this view by describing conjoint neuronal activities during action initiation or decision-making. Therefore, additional inves

Striatum plays an important role in the control of motor functions that are dependent on a balance between striatal dopamine and acetylcholine neuromodulators. The main source of acetylcholine in the striatum are cholinergic interneurons (CINs) which express heteromeric nicotinic acetylcholine receptors (nAChRs) containing beta2 subunit (beta2* nAChRs). Our group has previously shown that the deletion of beta2* nAChRs in CINs leads to behavioural changes in mice and to alterations of Fos expression in the striatum. Therefore, we hypothesize that the beta2 deletion leads to a decrease of CINs'

Sensorimotor regions of the neocortex send dense projections to the dorsal striatum making this region of basal ganglia an important structure of sensory integration. Anatomically, this innervation is diffuse, with axons from various cortical areas overlapping in the same striatal region. This suggests significant integration of information by striatal projection neurons (SPNs), contributing to the striatum’s role in decision making. However, the specific role of neurons forming direct and indirect pathways (d/iSPNs), as well as the level of convergence within one sensory modality onto single

The glycine receptor alpha 2 (GlyRα2) is the only functionally expressed glycine receptor in adult striatal projection neurons (SPNs) and an important modulator of signal integration within the dorsal striatum. SPNs are a convergence point for glutamatergic and dopaminergic input, which is key to reward-motivated behavior. Thus, targeting GlyRα2 offers great potential to modulate striatum-orchestrated behavior. However, the impact of GlyRα2's subcellular localization on SPN activity regulation remains unclear.Neurons are morphologically complex cells, containing many subcellular compartments (

The embryonic striatal development is a complex orchestrated process driven by a pattern of gene expression at neuronal progenitors. The correct maturation of striatal projection neurons (SPNs) that populate the striatum depends on their coordinated differentiation and their posterior organization into the striatal cytoarchitecture. Single-cell analysis can shed light into the physiology and pathology of striatal development, currently hampered by the heterogeneity of neural progenitors and the lack of gene markers. Here, we define for the first time the differentiation trajectories of SPNs by