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Postsynaptic potentiation of corticospinal projecting neurons in the anterior cingulate cortex after nerve injury

Tao Chen123, Kohei Koga13, Giannina Descalzi3, Shuang Qiu13, Jian Wang2, Le-Shi Zhang2, Zhi-Jian Zhang456, Xiao-Bin He47, Xin Qin8, Fu-Qiang Xu4567, Ji Hu1, Feng Wei9, Richard L Huganir10, Yun-Qing Li2* and Min Zhuo13*

Author Affiliations

1 Center for Neuron and Disease, Frontier Institute of Science and Technology, Xi’an Jiaotong University, Xi'an, China

2 Department of Anatomy, Histology and Embryology and K.K. Leung Brain Research Center, the Fourth Military Medical University, Xi’an 710032, China

3 Department of Physiology, Faculty of Medicine, Center for the Study of Pain, University of Toronto, 1 King’s College Circle, Toronto, Ontario M5S 1A8, Canada

4 Wuhan Institute of Physics and Mathematics, the Chinese Academy of Sciences, Wuhan 430071, China

5 Wuhan National Laboratory for Optoelectronics, Wuhan 430074, China

6 College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China

7 University of Chinese Academy of Sciences, Beijing 100049, China

8 College of Life Science, Wuhan University, Wuhan 430071, China

9 Department of Biomedical Sciences, University of Maryland Dental School, Baltimore, MD 21201, USA

10 Department of Neuroscience and Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA

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Molecular Pain 2014, 10:33  doi:10.1186/1744-8069-10-33

Published: 3 June 2014


Long-term potentiation (LTP) is the key cellular mechanism for physiological learning and pathological chronic pain. In the anterior cingulate cortex (ACC), postsynaptic recruitment or modification of AMPA receptor (AMPAR) GluA1 contribute to the expression of LTP. Here we report that pyramidal cells in the deep layers of the ACC send direct descending projecting terminals to the dorsal horn of the spinal cord (lamina I-III). After peripheral nerve injury, these projection cells are activated, and postsynaptic excitatory responses of these descending projecting neurons were significantly enhanced. Newly recruited AMPARs contribute to the potentiated synaptic transmission of cingulate neurons. PKA-dependent phosphorylation of GluA1 is important, since enhanced synaptic transmission was abolished in GluA1 phosphorylation site serine-845 mutant mice. Our findings provide strong evidence that peripheral nerve injury induce long-term enhancement of cortical-spinal projecting cells in the ACC. Direct top-down projection system provides rapid and profound modulation of spinal sensory transmission, including painful information. Inhibiting cortical top-down descending facilitation may serve as a novel target for treating neuropathic pain.