title: Coexistence of two forms of LTP in ACC provides a synaptic mechanism for the interactions between anxiety and chronic pain.
abstract: Chronic pain can lead to anxiety and anxiety can enhance the sensation of pain. Unfortunately, little is known about the synaptic mechanisms that mediate these re-enforcing interactions. Here we characterized two forms of long-term potentiation (LTP) in the anterior cingulate cortex (ACC); a presynaptic form (pre-LTP) that requires kainate receptors and a postsynaptic form (post-LTP) that requires N-methyl-D-aspartate receptors. Pre-LTP also involves adenylyl cyclase and protein kinase A and is expressed via a mechanism involving hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Interestingly, chronic pain and anxiety both result in selective occlusion of pre-LTP. Significantly, microinjection of the HCN blocker ZD7288 into the ACC in vivo produces both anxiolytic and analgesic effects. Our results provide a mechanism by which two forms of LTP in the ACC may converge to mediate the interaction between anxiety and chronic pain.
authors.affiliation: Center for Neuron and Disease, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China; Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors.forename: Kohei
authors.initials: K
authors.lastname: Koga
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors.forename: Giannina
authors.initials: G
authors.lastname: Descalzi
authors.affiliation: Center for Neuron and Disease, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China; Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 151-747, Korea.
authors.forename: Hyoung-Gon
authors.initials: HG
authors.lastname: Ko
authors.affiliation: Center for Neuron and Disease, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.
authors.forename: Jinshan
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors.forename: Shermaine
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 151-747, Korea.
authors.forename: Junehee
authors.initials: J
authors.lastname: Son
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 151-747, Korea.
authors.forename: TaeHyun
authors.initials: T
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 151-747, Korea.
authors.forename: Chuljung
authors.initials: C
authors.lastname: Kwak
authors.affiliation: Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Huganir
authors.affiliation: Department of Pharmacology, School of Pharmacy, The Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Ming-Gao
authors.initials: MG
authors.lastname: Zhao
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul 151-747, Korea.
authors.forename: Bong-Kiun
authors.initials: BK
authors.lastname: Kaang
authors.affiliation: Centre for Synaptic Plasticity, School of Physiology and Pharmacology, University of Bristol, Bristol, BS8 1TD, UK.
authors.forename: Graham L
authors.initials: GL
authors.lastname: Collingridge
authors.affiliation: Center for Neuron and Disease, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China; Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada. Electronic address: minzhuo10@gmail.com.
authors.forename: Min
authors.initials: M
authors.lastname: Zhuo
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001007:Anxiety / Q000378:metabolism* / Q000503:physiopathology; D059350:Chronic Pain / Q000378:metabolism* / Q000503:physiopathology; D006179:Gyrus Cinguli / Q000378:metabolism* / Q000503:physiopathology; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000502:physiology*; D051379:Mice; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D011743:Pyrimidines / Q000494:pharmacology; D018092:Kainic Acid Receptors / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D000700:Analgesics; D014151:Anti-Anxiety Agents; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D011743:Pyrimidines; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; C082246:ICI D2788