title: Deactivation of excitatory neurons in the prelimbic cortex via Cdk5 promotes pain sensation and anxiety.
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.
authors.affiliation: Neuroscience Research Institute and Department of Neurobiology, Key Laboratory for Neuroscience of Ministry of Education and Neuroscience, National Health and Family Planning Commission, Peking University, Beijing 100191, China.
authors.forename: Guo-Qiang
authors.initials: GQ
authors.lastname: Wang
authors.affiliation: Neuroscience Research Institute and Department of Neurobiology, Key Laboratory for Neuroscience of Ministry of Education and Neuroscience, National Health and Family Planning Commission, Peking University, Beijing 100191, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Cen
authors.affiliation: Neuroscience Research Institute and Department of Neurobiology, Key Laboratory for Neuroscience of Ministry of Education and Neuroscience, National Health and Family Planning Commission, Peking University, Beijing 100191, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Li
authors.affiliation: Neuroscience Research Institute and Department of Neurobiology, Key Laboratory for Neuroscience of Ministry of Education and Neuroscience, National Health and Family Planning Commission, Peking University, Beijing 100191, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Cao
authors.affiliation: Neuroscience Research Institute and Department of Neurobiology, Key Laboratory for Neuroscience of Ministry of Education and Neuroscience, National Health and Family Planning Commission, Peking University, Beijing 100191, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.affiliation: Shenzhen Key Lab of Neuropsychiatric Modulation, CAS Center for Excellence in Brain Science, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Shenzhen Key Lab of Neuropsychiatric Modulation, CAS Center for Excellence in Brain Science, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
authors.forename: Xue-Mei
authors.initials: XM
authors.lastname: Liu
authors.affiliation: Neuroscience Research Institute and Department of Neurobiology, Key Laboratory for Neuroscience of Ministry of Education and Neuroscience, National Health and Family Planning Commission, Peking University, Beijing 100191, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Neuroscience Research Institute and Department of Neurobiology, Key Laboratory for Neuroscience of Ministry of Education and Neuroscience, National Health and Family Planning Commission, Peking University, Beijing 100191, China.
authors.forename: Na-Xi
authors.initials: NX
authors.lastname: Tian
authors.affiliation: Neuroscience Research Institute and Department of Neurobiology, Key Laboratory for Neuroscience of Ministry of Education and Neuroscience, National Health and Family Planning Commission, Peking University, Beijing 100191, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Anatomy and Histology, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Shenzhen Key Lab of Neuropsychiatric Modulation, CAS Center for Excellence in Brain Science, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Wang
authors.affiliation: 1] Neuroscience Research Institute and Department of Neurobiology, Key Laboratory for Neuroscience of Ministry of Education and Neuroscience, National Health and Family Planning Commission, Peking University, Beijing 100191, China. [2] PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D001007:Anxiety / Q000235:genetics* / Q000378:metabolism / Q000523:psychology; D001522:Behavior, Animal; D059350:Chronic Pain / Q000235:genetics* / Q000378:metabolism / Q000523:psychology; D051360:Cyclin-Dependent Kinase 5 / Q000235:genetics*; D005106:Exploratory Behavior; D055785:Gene Knockdown Techniques; D006930:Hyperalgesia / Q000235:genetics* / Q000378:metabolism / Q000523:psychology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism*; D062308:Optogenetics; D018408:Patch-Clamp Techniques; D017397:Prefrontal Cortex / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D051360:Cyclin-Dependent Kinase 5; C495907:Cdk5 protein, rat