Parvalbumin + neurons and Npas1 + neurons are distinct neuron classes in the mouse external globus pallidus

Vivian M. Hernández, Daniel J. Hegeman, Qiaoling Cui, Daniel A. Kelver, Michael P. Fiske, Kelly E. Glajch, Jason E. Pitt, Tina Y. Huang, Nicholas J. Justice, C. Savio Chan*

*Corresponding author for this work

Research output: Contribution to journalArticle

44 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)11830-11847
Number of pages18
JournalJournal of Neuroscience
Volume35
Issue number34
DOIs
StatePublished - Aug 26 2015

Keywords

  • 6-OHDA
  • BAC transgenic mice
  • HCN
  • Intrinsic properties
  • Kv4
  • Nav

ASJC Scopus subject areas

  • Neuroscience(all)

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    Hernández, V. M., Hegeman, D. J., Cui, Q., Kelver, D. A., Fiske, M. P., Glajch, K. E., Pitt, J. E., Huang, T. Y., Justice, N. J., & Savio Chan, C. (2015). Parvalbumin + neurons and Npas1 + neurons are distinct neuron classes in the mouse external globus pallidus. Journal of Neuroscience, 35(34), 11830-11847. https://doi.org/10.1523/JNEUROSCI.4672-14.2015