title: Parvalbumin+ Neurons and Npas1+ Neurons Are Distinct Neuron Classes in the Mouse External Globus Pallidus.
abstract: Compelling evidence suggests that pathological activity of the external globus pallidus (GPe), a nucleus in the basal ganglia, contributes to the motor symptoms of a variety of movement disorders such as Parkinson's disease. Recent studies have challenged the idea that the GPe comprises a single, homogenous population of neurons that serves as a simple relay in the indirect pathway. However, we still lack a full understanding of the diversity of the neurons that make up the GPe. Specifically, a more precise classification scheme is needed to better describe the fundamental biology and function of different GPe neuron classes. To this end, we generated a novel multicistronic BAC (bacterial artificial chromosome) transgenic mouse line under the regulatory elements of the Npas1 gene. Using a combinatorial transgenic and immunohistochemical approach, we discovered that parvalbumin-expressing neurons and Npas1-expressing neurons in the GPe represent two nonoverlapping cell classes, amounting to 55% and 27% of the total GPe neuron population, respectively. These two genetically identified cell classes projected primarily to the subthalamic nucleus and to the striatum, respectively. Additionally, parvalbumin-expressing neurons and Npas1-expressing neurons were distinct in their autonomous and driven firing characteristics, their expression of intrinsic ion conductances, and their responsiveness to chronic 6-hydroxydopamine lesion. In summary, our data argue that parvalbumin-expressing neurons and Npas1-expressing neurons are two distinct functional classes of GPe neurons. This work revises our understanding of the GPe, and provides the foundation for future studies of its function and dysfunction.
  
  
  CONCLUSIONS
  Until recently, the heterogeneity of the constituent neurons within the external globus pallidus (GPe) was not fully appreciated. We addressed this knowledge gap by discovering two principal GPe neuron classes, which were identified by their nonoverlapping expression of the markers parvalbumin and Npas1. Our study provides evidence that parvalbumin and Npas1 neurons have different topologies within the basal ganglia.
authors: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, and.
authors: Vivian M
authors: VM
authors: Hernández
authors: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, and.
authors: Daniel J
authors: DJ
authors: Hegeman
authors: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, and.
authors: Qiaoling
authors: Q
authors: Cui
authors: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, and.
authors: Daniel A
authors: DA
authors: Kelver
authors: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, and.
authors: Michael P
authors: MP
authors: Fiske
authors: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, and.
authors: Kelly E
authors: KE
authors: Glajch
authors: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, and.
authors: Jason E
authors: JE
authors: Pitt
authors: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, and.
authors: Tina Y
authors: TY
authors: Huang
authors: Institute of Molecular Medicine, University of Texas, Houston, Texas 77030.
authors: Nicholas J
authors: NJ
authors: Justice
authors: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, and saviochan@gmail.com.
authors: C Savio
authors: http://orcid.org/0000-0002-3474-1718
authors: CS
authors: Chan
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000032:analysis / Q000096:biosynthesis*; D005260:Female; D005917:Globus Pallidus / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000096:biosynthesis*; D009474:Neurons / Q000737:chemistry / Q000145:classification* / Q000378:metabolism*; D010320:Parvalbumins / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D009419:Nerve Tissue Proteins; D010320:Parvalbumins; C512770:Npas1 protein, mouse
keywords: 6-OHDA; BAC transgenic mice; HCN; Kv4; Nav; intrinsic properties