Parvalbumin+ Neurons and Npas1+ Neurons Are Distinct Neuron Classes in the Mouse External Globus Pallidus. 2015

Vivian M Hernández, and Daniel J Hegeman, and Qiaoling Cui, and Daniel A Kelver, and Michael P Fiske, and Kelly E Glajch, and Jason E Pitt, and Tina Y Huang, and Nicholas J Justice, and C Savio Chan
Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, and.

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.

UI MeSH Term Description Entries
D008297 Male Males
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D008822 Mice, Transgenic Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN. Transgenic Mice,Founder Mice, Transgenic,Mouse, Founder, Transgenic,Mouse, Transgenic,Mice, Transgenic Founder,Transgenic Founder Mice,Transgenic Mouse
D009419 Nerve Tissue Proteins Proteins, Nerve Tissue,Tissue Proteins, Nerve
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D010320 Parvalbumins Low molecular weight, calcium binding muscle proteins. Their physiological function is possibly related to the contractile process. Parvalbumin,Parvalbumin B
D005260 Female Females
D005917 Globus Pallidus The representation of the phylogenetically oldest part of the corpus striatum called the paleostriatum. It forms the smaller, more medial part of the lentiform nucleus. Paleostriatum,Pallidum,Pallidums
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

Related Publications

Vivian M Hernández, and Daniel J Hegeman, and Qiaoling Cui, and Daniel A Kelver, and Michael P Fiske, and Kelly E Glajch, and Jason E Pitt, and Tina Y Huang, and Nicholas J Justice, and C Savio Chan
April 2017, Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology,
Vivian M Hernández, and Daniel J Hegeman, and Qiaoling Cui, and Daniel A Kelver, and Michael P Fiske, and Kelly E Glajch, and Jason E Pitt, and Tina Y Huang, and Nicholas J Justice, and C Savio Chan
October 2017, eLife,
Vivian M Hernández, and Daniel J Hegeman, and Qiaoling Cui, and Daniel A Kelver, and Michael P Fiske, and Kelly E Glajch, and Jason E Pitt, and Tina Y Huang, and Nicholas J Justice, and C Savio Chan
October 2020, The Journal of neuroscience : the official journal of the Society for Neuroscience,
Vivian M Hernández, and Daniel J Hegeman, and Qiaoling Cui, and Daniel A Kelver, and Michael P Fiske, and Kelly E Glajch, and Jason E Pitt, and Tina Y Huang, and Nicholas J Justice, and C Savio Chan
January 2023, Cell reports,
Vivian M Hernández, and Daniel J Hegeman, and Qiaoling Cui, and Daniel A Kelver, and Michael P Fiske, and Kelly E Glajch, and Jason E Pitt, and Tina Y Huang, and Nicholas J Justice, and C Savio Chan
February 2014, The Journal of neuroscience : the official journal of the Society for Neuroscience,
Vivian M Hernández, and Daniel J Hegeman, and Qiaoling Cui, and Daniel A Kelver, and Michael P Fiske, and Kelly E Glajch, and Jason E Pitt, and Tina Y Huang, and Nicholas J Justice, and C Savio Chan
January 2016, PloS one,
Vivian M Hernández, and Daniel J Hegeman, and Qiaoling Cui, and Daniel A Kelver, and Michael P Fiske, and Kelly E Glajch, and Jason E Pitt, and Tina Y Huang, and Nicholas J Justice, and C Savio Chan
April 2015, The Journal of neuroscience : the official journal of the Society for Neuroscience,
Vivian M Hernández, and Daniel J Hegeman, and Qiaoling Cui, and Daniel A Kelver, and Michael P Fiske, and Kelly E Glajch, and Jason E Pitt, and Tina Y Huang, and Nicholas J Justice, and C Savio Chan
September 1994, Brain research,
Vivian M Hernández, and Daniel J Hegeman, and Qiaoling Cui, and Daniel A Kelver, and Michael P Fiske, and Kelly E Glajch, and Jason E Pitt, and Tina Y Huang, and Nicholas J Justice, and C Savio Chan
January 2007, Progress in brain research,
Vivian M Hernández, and Daniel J Hegeman, and Qiaoling Cui, and Daniel A Kelver, and Michael P Fiske, and Kelly E Glajch, and Jason E Pitt, and Tina Y Huang, and Nicholas J Justice, and C Savio Chan
May 1999, Neuroreport,
Copied contents to your clipboard!