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Biomedicines
Volume 13
Issue 8
10.3390/biomedicines13081943
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Red Nucleus Excitatory Neurons Initiate Directional Motor Movement in Mice

by
Chenzhao He
1,†,
Guibo Qi
1,†,
Xin He
1,†,
Wenwei Shao
1,
Chao Ma
1,
Zhangfan Wang
1,
Haochuan Wang
1,
Yuntong Tan
1,
Li Yu
1,
Yongsheng Xie
2,*,
Song Qin
1,3,* and
Liang Chen
1,*
1
Department of Anatomy and Histology Embryology , School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
2
Neurosurgical Institute, Fudan University, Shanghai 200040, China
3
State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai 200032, China
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Biomedicines 2025, 13(8), 1943; https://doi.org/10.3390/biomedicines13081943
Submission received: 12 June 2025 / Revised: 25 July 2025 / Accepted: 4 August 2025 / Published: 8 August 2025
(This article belongs to the Special Issue Animal Models for Neurological Disease Research)
Versions Notes

Abstract

Background: The red nucleus (RN) is a phylogenetically conserved structure within the midbrain that is traditionally associated with general motor coordination; however, its specific role in controlling directional movement remains poorly understood. Methods: This study systematically investigates the function and mechanism of RN neurons in directional movement by combining stereotactic brain injections, fiber photometry recordings, multi-unit in vivo electrophysiological recordings, optogenetic manipulation, and anterograde trans-synaptic tracing. Results: We analyzed mice performing standardized T-maze turning tasks and revealed that anatomically distinct RN neuronal ensembles exhibit direction-selective activity patterns. These neurons demonstrate preferential activation during ipsilateral turning movements, with activity onset consistently occurring after movement initiation. We establish a causal relationship between RN neuronal activity and directional motor control: selective activation of RN glutamatergic neurons facilitates ipsilateral turning, whereas temporally precise inhibition significantly impairs the execution of these movements. Anterograde trans-synaptic tracing using H129 reveals that RN neurons selectively project to spinal interneuron populations responsible for ipsilateral flexion and coordinated limb movements. Conclusions: These findings offer a framework for understanding asymmetric motor control in the brain. This work redefines the RN as a specialized hub within midbrain networks that mediate lateralized movements and offers new avenues for neuromodulatory treatments for neurodegenerative and post-injury motor disorders.
Keywords: red nucleus; excitatory neurons; lateralized movement; anterograde red nucleus; excitatory neurons; lateralized movement; anterograde

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MDPI and ACS Style

He, C.; Qi, G.; He, X.; Shao, W.; Ma, C.; Wang, Z.; Wang, H.; Tan, Y.; Yu, L.; Xie, Y.; et al. Red Nucleus Excitatory Neurons Initiate Directional Motor Movement in Mice. Biomedicines 2025, 13, 1943. https://doi.org/10.3390/biomedicines13081943

AMA Style

He C, Qi G, He X, Shao W, Ma C, Wang Z, Wang H, Tan Y, Yu L, Xie Y, et al. Red Nucleus Excitatory Neurons Initiate Directional Motor Movement in Mice. Biomedicines. 2025; 13(8):1943. https://doi.org/10.3390/biomedicines13081943

Chicago/Turabian Style

He, Chenzhao, Guibo Qi, Xin He, Wenwei Shao, Chao Ma, Zhangfan Wang, Haochuan Wang, Yuntong Tan, Li Yu, Yongsheng Xie, and et al. 2025. "Red Nucleus Excitatory Neurons Initiate Directional Motor Movement in Mice" Biomedicines 13, no. 8: 1943. https://doi.org/10.3390/biomedicines13081943

APA Style

He, C., Qi, G., He, X., Shao, W., Ma, C., Wang, Z., Wang, H., Tan, Y., Yu, L., Xie, Y., Qin, S., & Chen, L. (2025). Red Nucleus Excitatory Neurons Initiate Directional Motor Movement in Mice. Biomedicines, 13(8), 1943. https://doi.org/10.3390/biomedicines13081943

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