Topographic connectivity and cellular profiling reveal detailed input pathways and functionally distinct cell types in the subthalamic nucleus

Hyungju Jeon; Hojin Lee; Dae-Hyuk Kwon; Jiwon Kim; Keiko Tanaka-Yamamoto; Jang Soo Yook; Linqing Feng; Hye Ran Park; Yong Hoon Lim; Zang-Hee Cho; Sun Ha Paek; Jinhyun Kim

doi:10.1016/j.celrep.2022.110439

Topographic connectivity and cellular profiling reveal detailed input pathways and functionally distinct cell types in the subthalamic nucleus

Cell Rep. 2022 Mar 1;38(9):110439. doi: 10.1016/j.celrep.2022.110439.

Authors

Affiliations

¹ Brain Science Institute, Korea Institute of Science and Technology (KIST), 39-1 Hawolgokdong, Seongbukgu, Seoul 02792 Korea.
² Brain Science Institute, Korea Institute of Science and Technology (KIST), 39-1 Hawolgokdong, Seongbukgu, Seoul 02792 Korea; Division of Bio-Medical Science & Technology, KIST School, University of Science and Technology, Seoul 02792, Korea.
³ Neuroscience Convergence Center, Korea University, Seoul 02841, Korea.
⁴ Soonchunhyang University Seoul Hospital, Seoul 04401, Korea.
⁵ Neurosurgery, Movement Disorder Center, Seoul National University College of Medicine, Advanced Institute of Convergence Technology (AICT), Seoul National University, Seoul 03080, Korea.
⁶ Brain Science Institute, Korea Institute of Science and Technology (KIST), 39-1 Hawolgokdong, Seongbukgu, Seoul 02792 Korea; Division of Bio-Medical Science & Technology, KIST School, University of Science and Technology, Seoul 02792, Korea. Electronic address: jinnykim@me.com.

PMID: 35235786
DOI: 10.1016/j.celrep.2022.110439

Abstract

The subthalamic nucleus (STN) controls psychomotor activity and is an efficient therapeutic deep brain stimulation target in individuals with Parkinson's disease. Despite evidence indicating position-dependent therapeutic effects and distinct functions within the STN, the input circuit and cellular profile in the STN remain largely unclear. Using neuroanatomical techniques, we construct a comprehensive connectivity map of the indirect and hyperdirect pathways in the mouse STN. Our circuit- and cellular-level connectivities reveal a topographically graded organization with three types of indirect and hyperdirect pathways (external globus pallidus only, STN only, and collateral). We confirm consistent pathways into the human STN by 7 T MRI-based tractography. We identify two functional types of topographically distinct glutamatergic STN neurons (parvalbumin [PV+/-]) with synaptic connectivity from indirect and hyperdirect pathways. Glutamatergic PV+ STN neurons contribute to burst firing. These data suggest a complex interplay of information integration within the basal ganglia underlying coordinated movement control and therapeutic effects.

Keywords: cell type; connectivity; firing pattern; indirect and hyperdirect pathways; subthalamic nucleus.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Basal Ganglia / physiology
Globus Pallidus
Mice
Neural Pathways / physiology
Neurons / physiology
Subthalamic Nucleus*