title: Bidirectional modulation of hyperalgesia via the specific control of excitatory and inhibitory neuronal activity in the ACC.
abstract: Neurons in the anterior cingulate cortex (ACC) are assumed to play important roles in the perception of nociceptive signals and the associated emotional responses. However, the neuronal types within the ACC that mediate these functions are poorly understood. In the present study, we used optogenetic techniques to selectively modulate excitatory pyramidal neurons and inhibitory interneurons in the ACC and to assess their ability to modulate peripheral mechanical hypersensitivity in freely moving mice. We found that selective activation of pyramidal neurons rapidly and acutely reduced nociceptive thresholds and that this effect was occluded in animals made hypersensitive using Freund's Complete Adjuvant (CFA). Conversely, inhibition of ACC pyramidal neurons rapidly and acutely reduced hypersensitivity induced by CFA treatment. A similar analgesic effect was induced by activation of parvalbumin (PV) expressing interneurons, whereas activation of somatostatin (SOM) expressing interneurons had no effect on pain thresholds. Our results provide direct evidence of the pivotal role of ACC excitatory neurons, and their regulation by PV expressing interneurons, in nociception.
authors.affiliation: Department of Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul, 151-746, South Korea.
authors.forename: Sukjae Joshua
authors.initials: SJ
authors.lastname: Kang
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, 151-747, South Korea.
authors.forename: Chuljung
authors.initials: C
authors.lastname: Kwak
authors.affiliation: Interdisciplinary Program in Neuroscience, College of Natural Sciences, Seoul National University, Seoul, 151-747, South Korea.
authors.forename: Jaehyun
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul, 151-746, South Korea.
authors.forename: Su-Eon
authors.initials: SE
authors.lastname: Sim
authors.affiliation: Department of Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul, 151-746, South Korea.
authors.forename: Jaehoon
authors.initials: J
authors.lastname: Shim
authors.affiliation: Interdisciplinary Program in Neuroscience, College of Natural Sciences, Seoul National University, Seoul, 151-747, South Korea.
authors.forename: Taehyuk
authors.initials: T
authors.lastname: Choi
authors.affiliation: Centre for Synaptic Plasticity, School of Physiology and Pharmacology, University of Bristol, Bristol, BS8 1TD, UK. glcollingridge@gmail.com.|Center for Neuron and Disease, Frontier Institutes of Life Science and of Science and Technology, Xi'an Jiaotong University, Xi'an, China. glcollingridge@gmail.com.|Department of Physiology, Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada. glcollingridge@gmail.com.|Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Ontario M5G 1X5, Toronto, ON, M5S 1A8, Canada. glcollingridge@gmail.com.
authors.forename: Graham L
authors.initials: GL
authors.lastname: Collingridge
authors.affiliation: Center for Neuron and Disease, Frontier Institutes of Life Science and of Science and Technology, Xi'an Jiaotong University, Xi'an, China. min.zhuo@utoronto.ca.|Department of Physiology, Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada. min.zhuo@utoronto.ca.
authors.forename: Min
authors.initials: M
authors.lastname: Zhuo
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, 151-747, South Korea. kaang@snu.ac.kr.|Center for Neuron and Disease, Frontier Institutes of Life Science and of Science and Technology, Xi'an Jiaotong University, Xi'an, China. kaang@snu.ac.kr.
authors.forename: Bong-Kiun
authors.initials: BK
authors.lastname: Kaang
mesh_terms: D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D059350:Chronic Pain / Q000473:pathology / Q000503:physiopathology; D005620:Freund's Adjuvant; D006179:Gyrus Cinguli / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D006930:Hyperalgesia / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D007249:Inflammation / Q000473:pathology; D019426:Integrases / Q000378:metabolism; D007395:Interneurons / Q000378:metabolism; D008297:Male; D051379:Mice; D009433:Neural Inhibition; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D062308:Optogenetics; D017288:Pain Threshold; D010320:Parvalbumins / Q000378:metabolism; D012243:Rhodopsin / Q000378:metabolism
chemical_list: D010320:Parvalbumins; D005620:Freund's Adjuvant; D012243:Rhodopsin; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; C045073:Cre recombinase; D019426:Integrases