Abstract
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 language | English (US) |
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Pages (from-to) | 743-768 |
Number of pages | 26 |
Journal | Journal of Neuroscience |
Volume | 40 |
Issue number | 4 |
DOIs | |
State | Published - Jan 22 2020 |
Funding
This work was supported by the National Institutes of Health (Grants R01 NS069777 to C.S.C., P50 NS047085 to C.S.C., R01 MH112768 to C.S.C., R01 NS097901 to C.S.C., R01 MH109466 to C.S.C., R01 NS088528 to C.S.C., R01 NS096240 to R.A., R01 MH110556 to R.A., P50 DA044121 to R.A., R01 MH107742 to B.L., R01 MH108594 to B.K.L., U01 MH114829 to B.K.L., R01 MH116176 to Y.K., R01 MH112768 to N.J.J., R56 MH114032 to N.J.J., R21 AA026022 to N.J.J., R01 NS103993 to B.M.H., ZIA MH002497 to C.R.G., T32 NS041234 to H.S.X., F32 NS098793 to H.S.X., and T32 AG020506 to A.P.), a NARSAD Young Investigator Award to B.M.H., a Howard Hughes Medical Institute HHMI-PF Medical Research Fellowship to Z.A.A., an AΩA Student Research Fellowship to Z.A.A., and a Northwestern University Weinberg Summer Research Grant to P.H.W. We thank Xixun Du, Yu Zhang, Vishnu Rangachari, Kris Shah, Elizabeth Augustine, and Daniel Hegeman for assistance on the project; Alexandria Granados, Morgan Marshall, and Nicole Curtis for colony management and technical support; Alicia Guemez-Gamboa for providing Emx1-Cre mice; Jeffrey Savas for providing VGluT1 antibody; and the Northwestern University Transgenic and Targeted Mutagenesis Laboratory for providing EIIa-Cre and CAG-Flp breeders. U01MH114829toB.K.L.,R01MH116176toY.K.,R01MH112768toN.J.J.,R56MH114032toN.J.J.,R21AA026022to N.J.J., R01 NS103993 to B.M.H., ZIA MH002497 to C.R.G., T32 NS041234 to H.S.X., F32 NS098793 to H.S.X., and T32 AG020506 to A.P.), a NARSAD Young Investigator Award to B.M.H., a Howard Hughes Medical Institute HHMI-PF MedicalResearchFellowshiptoZ.A.A.,anAΩAStudentResearchFellowshiptoZ.A.A.,andaNorthwesternUniver-sity Weinberg Summer Research Grant to P.H.W. We thank Xixun Du, Yu Zhang, Vishnu Rangachari, Kris Shah, ElizabethAugustine,andDanielHegemanforassistanceontheproject;AlexandriaGranados,MorganMarshall,and Nicole Curtis for colony management and technical support; Alicia Guemez-Gamboa for providing Emx1-Cre mice; JeffreySavasforprovidingVGluT1antibody;andtheNorthwesternUniversityTransgenicandTargetedMutagenesis Laboratory for providing EIIa-Cre and CAG-Flp breeders. The authors declare no competing financial interests. *Z.A.A. and B.L.B. contributed equally to this work. Correspondence should be addressed to C. Savio Chan at [email protected]. https://doi.org/10.1523/JNEUROSCI.1199-19.2019 Copyright © 2020 the authors This work was supported by the National Institutes of Health (Grants R01 NS069777 to C.S.C., P50 NS047085 to C.S.C., R01 MH112768 to C.S.C., R01 NS097901 to C.S.C., R01 MH109466 to C.S.C., R01 NS088528 to C.S.C., R01 NS096240 to R.A., R01 MH110556 to R.A., P50 DA044121 to R.A., R01 MH107742 to B.L., R01 MH108594 to B.K.L.,
Keywords
- arkypallidal neurons
- basal ganglia
- cellular diversity
- globus pallidus
- pallidocortical neurons
- prototypic neurons
ASJC Scopus subject areas
- General Neuroscience