Volume 33, No 10, Oct 2023

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 33 Issue 10, October 2023: 775-789   |  Open Access

ORIGINAL ARTICLES

A direct spino-cortical circuit bypassing the thalamus modulates nociception

Bing Cai^1,2,3,† , Dan Wu^4,† , Hong Xie^2,10,† , Yan Chen^1,2,3 , Huadong Wang⁵ , Sen Jin⁵ , Yuran Song^1,2,3 , Anan Li⁶ , Shiqi Huang^2,7 , Sashuang Wang⁸ , Yingjin Lu¹ , Lan Bao^1,7,9 , Fuqiang Xu⁵ , Hui Gong⁶ , Changlin Li^1,8,* , Xu Zhang^1,2,3,7,*

¹Guangdong Institute of Intelligence Science and Technology, Hengqin, Zhuhai, Guangdong, China
²SIMR Joint Lab of Drug Innovation, Shanghai Advanced Research Institute, Chinese Academy of Sciences (CAS); Xuhui Central Hospital, Shanghai, China
³Research Unit of Pain Medicine, Chinese Academy of Medical Sciences, Hengqin, Zhuhai, Guangdong, China
⁴Institute of Neuroscience and State Key Laboratory of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, CAS, Shanghai, China
⁵Shenzhen Key Laboratory of Viral Vectors for Biomedicine, Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, CAS, Shenzhen, Guangdong, China
⁶HUST-Suzhou Institute for Brainsmatics, JITRI Institute for Brainsmatics, Suzhou, Jiangsu, China
⁷School of Life Science and Technology, ShanghaiTech University, Shanghai, China
⁸Department of Pain Medicine and Shenzhen Municipal Key Laboratory for Pain Medicine, Shenzhen Nanshan People’s Hospital, Shenzhen, Guangdong, China
⁹State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, CAS, Shanghai, China
¹⁰Present address: Institute of Photonic Chips; School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai, China
^†These authors contributed equally: Bing Cai, Dan Wu, Hong Xie
Correspondence: Changlin Li(licl@gdiist.cn)Xu Zhang(zhangx@sari.ac.cn)

Nociceptive signals are usually transmitted to layer 4 neurons in somatosensory cortex via the spinothalamic-thalamocortical pathway. The layer 5 corticospinal neurons in sensorimotor cortex are reported to receive the output of neurons in superficial layers; and their descending axons innervate the spinal cord to regulate basic sensorimotor functions. Here, we show that a subset of layer 5 neurons receives spinal inputs through a direct spino-cortical circuit bypassing the thalamus, and thus define these neurons as spino-cortical recipient neurons (SCRNs). Morphological studies revealed that the branches from spinal ascending axons formed a kind of disciform structure with the descending axons from SCRNs in the basilar pontine nucleus (BPN). Electron microscopy and calcium imaging further confirmed that the axon terminals from spinal ascending neurons and SCRNs made functional synaptic contacts in the BPN, linking the ascending sensory pathway to the descending motor control pathway. Furthermore, behavioral tests indicated that the spino-cortical connection in the BPN was involved in nociceptive responses. In vivo calcium imaging showed that SCRNs responded to peripheral noxious stimuli faster than neighboring layer 4 cortical neurons in awake mice. Manipulating activities of SCRNs could modulate nociceptive behaviors. Therefore, this direct spino-cortical circuit represents a noncanonical pathway, allowing a fast sensory-motor transition of the brain in response to noxious stimuli.

https://doi.org/10.1038/s41422-023-00832-0

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