Npas1+-Nkx2.1+ Neurons Are an Integral Part of the Cortico-pallido-cortical Loop

Zachary A. Abecassis, Brianna L. Berceau, Phyo H. Win, Daniela García, Harry S. Xenias, Qiaoling Cui, Arin Pamukcu, Suraj Cherian, Vivian M. Hernández, Uree Chon, Byung Kook Lim, Yongsoo Kim, Nicholas J. Justice, Raj Awatramani, Bryan M. Hooks, Charles R. Gerfen, Simina M. Boca, C. Savio Chan

Research output: Contribution to journalArticlepeer-review

56 Scopus citations


Within the basal ganglia circuit, the external globus pallidus (GPe) is critically involved in motor control. Aside from Foxp2 + neurons and ChAT + neurons that have been established as unique neuron types, there is little 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 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. Importantly, tracing experiments revealed that Npas1 +-Nkx2.1 + neurons represent the principal noncholinergic, cortically-projecting neurons. In other words, they form the pallido-cortical arm of the cortico-pallido-cortical loop. Our data further show that pyramidal-tract neurons in the cortex collateralized within the GPe, forming a closed-loop system between the two brain structures. Overall, our findings reconcile some of the discrepancies that arose from differences in techniques or the reliance on preexisting tools. Although spatial distribution and electrophysiological properties of GPe neurons reaffirm the diversification of GPe subtypes, statistical analyses strongly support the notion that these neuron subtypes can be categorized under the two principal neuron classes: PV + neurons and Npas1 + neurons.

Original languageEnglish (US)
Pages (from-to)743-768
Number of pages26
JournalJournal of Neuroscience
Issue number4
StatePublished - Jan 22 2020

All Science Journal Classification (ASJC) codes

  • General Neuroscience


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