title: Elucidating an Affective Pain Circuit that Creates a Threat Memory.
abstract: Animals learn to avoid harmful situations by associating a neutral stimulus with a painful one, resulting in a stable threat memory. In mammals, this form of learning requires the amygdala. Although pain is the main driver of aversive learning, the mechanism that transmits pain signals to the amygdala is not well resolved. Here, we show that neurons expressing calcitonin gene-related peptide (CGRP) in the parabrachial nucleus are critical for relaying pain signals to the central nucleus of amygdala and that this pathway may transduce the affective motivational aspects of pain. Genetic silencing of CGRP neurons blocks pain responses and memory formation, whereas their optogenetic stimulation produces defensive responses and a threat memory. The pain-recipient neurons in the central amygdala expressing CGRP receptors are also critical for establishing a threat memory. The identification of the neural circuit conveying affective pain signals may be pertinent for treating pain conditions with psychiatric comorbidities.
authors.affiliation: Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
authors.forename: Sung
authors.initials: S
authors.lastname: Han
authors.affiliation: Graduate Program in Neuroscience, University of Washington, Seattle, WA 98195, USA.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Soleiman
authors.affiliation: Departments of Psychiatry and Pharmacology, University of Washington, Seattle, WA 98195, USA.
authors.forename: Marta E
authors.initials: ME
authors.lastname: Soden
authors.affiliation: Departments of Psychiatry and Pharmacology, University of Washington, Seattle, WA 98195, USA.
authors.forename: Larry S
authors.initials: LS
authors.lastname: Zweifel
authors.affiliation: Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Graduate Program in Neuroscience, University of Washington, Seattle, WA 98195, USA. Electronic address: palmiter@uw.edu.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Palmiter
mesh_terms: D000679:Amygdala / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal; D002116:Calcitonin / Q000235:genetics; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D003213:Conditioning, Psychological; D007858:Learning; D009434:Neural Pathways; D009474:Neurons / Q000502:physiology*; D010146:Pain / Q000503:physiopathology*; D065823:Parabrachial Nucleus / Q000502:physiology; D011498:Protein Precursors / Q000235:genetics
chemical_list: D011498:Protein Precursors; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide