Brain Structure and Function

, Volume 222, Issue 9, pp 4089–4110 | Cite as

Substance P effects exclusively on prototypic neurons in mouse globus pallidus

  • Kazuko Mizutani
  • Susumu Takahashi
  • Shinichiro Okamoto
  • Fuyuki KarubeEmail author
  • Fumino FujiyamaEmail author
Original Article


Previous studies have suggested that the neurokinin-1 receptor (NK-1R) expressing neurons in the globus pallidus (GP) receive substance P (SP), presumably released by axon collaterals of striatal direct neurons. However, the effect of SP on the GP remains unclear. In this study, we identified that the SP-responsive cells comprise a highly specific cell type in the GP with regard to immunofluorescence, electrophysiology, and projection properties. Morphologically, NK-1R-immunoreactive neurons occasionally co-expressed parvalbumin (PV) and/or Lim-homeobox 6 (Lhx6), but not Forkhead box protein P2 (FoxP2), which is mainly expressed by arkypallidal neurons. Retrograde tracing experiments also showed that some of GP neurons projecting to the subthalamic nucleus (namely prototypic neurons) expressed NK-1R as well as Lhx6 and/or PV, but not FoxP2. In vitro electrophysiological study revealed that, among 48 GP neurons, the SP agonist induced inward current in 21 neurons. The response was prevented by bath application of the NK-1R antagonist. Based on the firing properties, 92 recorded GP neurons were classified into three distinct types, i.e., CL1, 2, and 3. Interestingly, all the SP-responsive neurons were found to be in CL2 and CL3 types, but not in CL1. Moreover, active and passive membrane properties of the neurons in those clusters and immunofluorescent identification suggested that CL1 and CL2/3 could be considered as arkypallidal and prototypic neurons, respectively. Therefore, SP-responsive neurons were one of the populations of prototypic neurons based on both anatomical and electrophysiological results. Altogether, the striatal direct pathway neurons could affect the indirect pathway in the way of prototypic neurons, via the action of SP to NK-1R.


Neurokinin-1 receptor Globus pallidus Basal ganglia Striatum 



We thank Dr. H. Hioki (Kyoto University) and Dr. H. Kameda (Teikyo University) for providing the PV/myrGFP-LDLRct transgenic mice.

Compliance and ethical standards

Conflict of interest

The authors declare no competing financial interest.


This study was funded by Grants-in-Aid from The Ministry of Education, Culture, Sports, Science, and Technology (MEXT) for Scientific Research (25282247 and 15K12770 to FF; 26350983 and 16H01622 to FK; 25560435, 16H02840, 16H01623, 16K13115, 16H06543 to ST); MIC SCOPE (152107008) to ST; and for Scientific Researches on Innovative Areas “Adaptive Circuit Shift” (26112001) to FF.

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© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  1. 1.Laboratory of Neural Circuitry, Graduate School of Brain ScienceDoshisha UniversityKyotanabeJapan
  2. 2.Laboratory of Cognitive and Behavioral Neuroscience, Graduate School of Brain ScienceDoshisha UniversityKyotanabeJapan
  3. 3.Department of Morphological Brain Science, Graduate School of MedicineKyoto UniversityKyotoJapan

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