Volume 40, Issue 11, November, 2024


Glutamatergic Circuits in the Pedunculopontine Nucleus Modulate Multiple Motor Functions

 Yanwang Huang1,2  · Shangyi Wang1,2,3 · Qingxiu Wang1  · Chaowen Zheng1,2 · Feng Yang1,2 · Lei Wei1  · Xintong Zhou1,2,3 · Zuoren Wang1,2,3,4
1 Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China 
2 University of Chinese Academy of Sciences, Beijing 100049, China 
3 School of Future Technology, University of Chinese Academy of Sciences, Beijing 100049, China 
4 School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China

Abstract
The functional role of glutamatergic (vGluT2) neurons in the pedunculopontine nucleus (PPN) in modulating motor activity remains controversial. Here, we demonstrated that the activity of vGluT2 neurons in the rostral PPN is correlated with locomotion and ipsilateral head-turning. Beyond these motor functions, we found that these rostral PPN-vGluT2 neurons remarkably respond to salient stimuli. Furthermore, we systematically traced the upstream and downstream projections of these neurons and identified two downstream projections from these neurons to the caudal pontine reticular nucleus/anterior gigantocellular reticular nucleus (PnC/GiA) and the zona incerta (ZI). Our findings indicate that the projections to the PnC/GiA inhibit movement, consistent with ‘pause-and-play’ behavior, whereas those to the ZI promote locomotion, and others respond to a new ‘pause-switch-play’ pattern. Collectively, these findings elucidate the multifaceted influence of the PPN on motor functions and provide a robust theoretical framework for understanding its physiological and potential therapeutic implications.

Keywords
Pedunculopontine nucleus; Glutamatergic neuron; Pause-and-play; Caudal pontine reticular nucleus; Anterior gigantocellular reticular nucleus; Zona incerta