Modeling long-range human nigrostriatal connectivity reveals striatal target-dependent maturation of dopamine neurons

ABSTRACT: The human nigrostriatal pathway, comprising dopaminergic neurons in the ventral midbrain that project to the dorsolateral striatum, is essential for motor control and selectively vulnerable in Parkinson's disease. How this circuit assembles during human development remains poorly understood, and in vitro models capturing its long-range connectivity and spatial organization have been lacking. Here, we establish a compartmentalized, human stem cell-based model of the nigrostriatal pathway by integrating ventral midbrain and striatal organoids within a custom-engineered microfluidic device that confines cell bodies while guiding axonal growth to recapitulate key aspects of in vivo topography. Functional connectivity was confirmed by retrograde rabies tracing, and optogenetic and pharmacologic

SUBMITTER: Sara Corsi 

PROVIDER: S-SCDT-10_1038-S44318-026-00942-6 | biostudies-other |

REPOSITORIES: biostudies-other