Transgenic tools targeting striatal and pallidal subpopulations revealed evolutionary conservation and specialization of the cortico-basal ganglia circuit in zebrafish

The cortico-basal ganglia circuit mediates decision-making. Here, we generated transgenic tools for adult zebrafish targeting specific subpopulations of the components of this circuit and utilized them to identify evolutionary homologs of the mammalian direct- and indirect-pathway striatal neurons which respectively project to the homologs of the internal and external segment of the globus pallidus (dEN and Vl) as in mammals. Unlike in mammals, the Vl mainly projected to the dEN directly, not by way of the subthalamic nucleus. Further single-cell RNA sequencing analysis revealed two pallidal output pathways: a major shortcut pathway directly connecting the dEN with the pallium and the evolutionarily conserved closed loop by way of the thalamus. Our resources and circuit map provide the common basis for the functional study of the basal ganglia in a small and optically tractable zebrafish brain for the comprehensive mechanistic understanding of the cortico-basal ganglia circuit.