title: Pavlovian fear memory induced by activation in the anterior cingulate cortex.
abstract: Identifying higher brain central region(s) that are responsible for the unpleasantness of pain is the focus of many recent studies. Here we show that direct stimulation of the anterior cingulate cortex (ACC) in mice produced fear-like freezing responses and induced long-term fear memory, including contextual and auditory fear memory. Auditory fear memory required the activation of N-methyl-D-aspartate (NMDA) receptors in the amygdala. To test the hypothesis that neuronal activity in the ACC contributes to unpleasantness, we injected a GABAA receptor agonist, muscimol bilaterally into the ACC. Both contextual and auditory memories induced by foot shock were blocked. Furthermore, activation of metabotropic glutamate receptors in the ACC enhanced behavioral escape responses in a noxious hot-plate as well as spinal nociceptive tail-flick reflex. Our results provide strong evidence that the excitatory activity in the ACC contribute to pain-related fear memory as well as descending facilitatory modulation of spinal nociception.
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Toronto Centre for the Study of Pain, University of Toronto, Medical Sciences Building, Rm 3342, 1 King's College Circle, Toronto, ON M5S 1A8, Canada. jtang@cns.neusc.bcm.tmc.edu
authors.forename: Jianrong
authors.initials: J
authors.lastname: Tang
authors.forename: Shanelle
authors.initials: S
authors.lastname: Ko
authors.forename: Hoi-Ki
authors.initials: HK
authors.lastname: Ding
authors.forename: Chang-Shen
authors.initials: CS
authors.lastname: Qiu
authors.forename: Amelita A
authors.initials: AA
authors.lastname: Calejesan
authors.forename: Min
authors.initials: M
authors.lastname: Zhuo
mesh_terms: D000818:Animals; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D058785:GABA-A Receptor Agonists; D006179:Gyrus Cinguli / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009118:Muscimol / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D058785:GABA-A Receptor Agonists; D009118:Muscimol