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Npas1+-Nkx2. 1+ Neurons Form A Unique Pallidal Neuron Subclass

Abecassis, Z;Berceau, B;Win, J;Garcia, D;Xenias, H;

Within the basal ganglia circuit, the GPe is critically involved in motor control. Aside from Foxp2+ neurons and ChAT+ neurons that have been established as unique neuron types, there is no consensus on the classification of GPe neurons. Properties of the remaining neuron types are poorly defined. In this study, we leverage new mouse lines, viral tools, and molecular markers to study GPe neurons. By examining multiple modalities, we sought to better define GPe neuron subtypes. We found that Sox6 represents a novel, defining marker for GPe neuron subtypes. Lhx6+ neurons that lack the expression of Sox6 were devoid of both parvalbumin and Npas1. This result confirms previous assertions of the existence of a unique Lhx6+ population. Neurons that arise from the Dbx1+ lineage were similarly abundant in the GPe and displayed a heterogeneous makeup. Tracing experiments revealed that Npas1+-Nkx2.1+ neurons represent the principal, non-cholinergic, cortically-projecting neurons; they project profusely in the cortex and are part of a cortico-pallidal-cortical loop. Lastly, analysis of the spatial distribution and electrophysiological properties of a number of GPe neuron types further confirms the diversification of GPe subtypes. In summary, we provide improved descriptions of GPe neuron subtypes. By delineating different GPe neurons and their synaptic partners, our findings establish the circuit substrates that can be important for motor function and dysfunction. Our findings reconcile some of the discrepancies that arose from differences in techniques or the reliance on pre-existing tools.