Deactivation of excitatory neurons in the prelimbic cortex via Cdk5 promotes pain sensation and anxiety

Guo-Qiang Wang, Cheng Cen, Chong Li, Shuai Cao, Ning Wang, Zheng Zhou, Xue-Mei Liu, Yu Xu, Na-Xi Tian, Ying Zhang, Jun Wang, Li-Ping Wang () and Yun Wang ()
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Guo-Qiang Wang: Key Laboratory for Neuroscience of Ministry of Education and Neuroscience, National Health and Family Planning Commission, Peking University
Cheng Cen: Key Laboratory for Neuroscience of Ministry of Education and Neuroscience, National Health and Family Planning Commission, Peking University
Chong Li: Key Laboratory for Neuroscience of Ministry of Education and Neuroscience, National Health and Family Planning Commission, Peking University
Shuai Cao: Key Laboratory for Neuroscience of Ministry of Education and Neuroscience, National Health and Family Planning Commission, Peking University
Ning Wang: Key Laboratory for Neuroscience of Ministry of Education and Neuroscience, National Health and Family Planning Commission, Peking University
Zheng Zhou: Shenzhen Key Lab of Neuropsychiatric Modulation, CAS Center for Excellence in Brain Science, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences
Xue-Mei Liu: Shenzhen Key Lab of Neuropsychiatric Modulation, CAS Center for Excellence in Brain Science, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences
Yu Xu: Key Laboratory for Neuroscience of Ministry of Education and Neuroscience, National Health and Family Planning Commission, Peking University
Na-Xi Tian: Key Laboratory for Neuroscience of Ministry of Education and Neuroscience, National Health and Family Planning Commission, Peking University
Ying Zhang: Key Laboratory for Neuroscience of Ministry of Education and Neuroscience, National Health and Family Planning Commission, Peking University
Jun Wang: School of Basic Medical Sciences, Peking University
Li-Ping Wang: Shenzhen Key Lab of Neuropsychiatric Modulation, CAS Center for Excellence in Brain Science, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences
Yun Wang: Key Laboratory for Neuroscience of Ministry of Education and Neuroscience, National Health and Family Planning Commission, Peking University

Nature Communications, 2015, vol. 6, issue 1, 1-16

Abstract: Abstract The medial prefrontal cortex (mPFC) is implicated in processing sensory-discriminative and affective pain. Nonetheless, the underlying mechanisms are poorly understood. Here we demonstrate a role for excitatory neurons in the prelimbic cortex (PL), a sub-region of mPFC, in the regulation of pain sensation and anxiety-like behaviours. Using a chronic inflammatory pain model, we show that lesion of the PL contralateral but not ipsilateral to the inflamed paw attenuates hyperalgesia and anxiety-like behaviours in rats. Optogenetic activation of contralateral PL excitatory neurons exerts analgesic and anxiolytic effects in mice subjected to chronic pain, whereas inhibition is anxiogenic in naive mice. The intrinsic excitability of contralateral PL excitatory neurons is decreased in chronic pain rats; knocking down cyclin-dependent kinase 5 reverses this deactivation and alleviates behavioural impairments. Together, our findings provide novel insights into the role of PL excitatory neurons in the regulation of sensory and affective pain.

Date: 2015
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DOI: 10.1038/ncomms8660

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