RT Journal Article
SR Electronic
T1 Npas1<sup>+</sup>-Nkx2.1<sup>+</sup> Neurons Are an Integral Part of the Cortico-pallido-cortical Loop
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 743
OP 768
DO 10.1523/JNEUROSCI.1199-19.2019
VO 40
IS 4
A1 Zachary A. Abecassis
A1 Brianna L. Berceau
A1 Phyo H. Win
A1 Daniela García
A1 Harry S. Xenias
A1 Qiaoling Cui
A1 Arin Pamukcu
A1 Suraj Cherian
A1 Vivian M. Hernández
A1 Uree Chon
A1 Byung Kook Lim
A1 Yongsoo Kim
A1 Nicholas J. Justice
A1 Raj Awatramani
A1 Bryan M. Hooks
A1 Charles R. Gerfen
A1 Simina M. Boca
A1 C. Savio Chan
YR 2020
UL http://www.jneurosci.org/content/40/4/743.abstract
AB 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.SIGNIFICANCE STATEMENT The poor understanding of the neuronal composition in the external globus pallidus (GPe) undermines our ability to interrogate its precise behavioral and disease involvements. In this study, 12 different genetic crosses were used, hundreds of neurons were electrophysiologically characterized, and &gt;100,000 neurons were histologically- and/or anatomically-profiled. Our current study further establishes the segregation of GPe neuron classes and illustrates the complexity of GPe neurons in adult mice. Our results support the idea that Npas1+–Nkx2.1+ neurons are a distinct GPe neuron subclass. By providing a detailed analysis of the organization of the cortico-pallidal-cortical projection, our findings establish the cellular and circuit substrates that can be important for motor function and dysfunction.