title: Amygdala-Dependent Molecular Mechanisms of the Tac2 Pathway in Fear Learning.
abstract: Recently we determined that activation of the tachykinin 2 (Tac2) pathway in the central amygdala (CeA) is necessary and sufficient for the modulation of fear memories. The Tac2 pathway includes the Tac2 gene, which encodes the neuropeptide neurokinin B and its corresponding receptor neurokinin 3 receptor (NK3R). In this study, using Tac2-cre and Tac2-GFP mice, we applied a combination of in vivo (optogenetics) and multiple in vitro techniques to further explore the mechanisms of action within the Tac2 pathway. In transgenic mice that express ChR2 solely in Tac2 neurons, in vivo optogenetic stimulation of CeA Tac2-expressing neurons during fear acquisition enhanced fear memory consolidation and drove action potential firing in vitro. In addition, Tac2-CeA neurons were shown to co-express striatal-enriched protein tyrosine phosphatase, which may have an important role in regulating Nk3R signaling during fear conditioning. These data extend our current understanding for the underlying mechanism(s) for the role of the Tac2 pathway in the regulation of fear memory, which may serve as a new therapeutic target in the treatment of fear-related disorders.
authors.affiliation: Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, MA, USA.|Division of Behavioral Neuroscience and Psychiatric Disorders, Yerkes National Primate Research Center, Atlanta, GA, USA.|Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.|Institut de Neurociènces, Universitat Autònoma de Barcelona, Bellaterra, Spain.
authors.forename: Raül
authors.initials: R
authors.lastname: Andero
authors.affiliation: Division of Behavioral Neuroscience and Psychiatric Disorders, Yerkes National Primate Research Center, Atlanta, GA, USA.|Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Daniel
authors.affiliation: Division of Behavioral Neuroscience and Psychiatric Disorders, Yerkes National Primate Research Center, Atlanta, GA, USA.|Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Ji-Dong
authors.initials: JD
authors.lastname: Guo
authors.affiliation: Division of Behavioral Neuroscience and Psychiatric Disorders, Yerkes National Primate Research Center, Atlanta, GA, USA.|Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Bruner
authors.affiliation: Division of Behavioral Neuroscience and Psychiatric Disorders, Yerkes National Primate Research Center, Atlanta, GA, USA.|Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Shivani
authors.initials: S
authors.lastname: Seth
authors.affiliation: Department of Pharmacology and Physiology, George Washington University, Washington, DC, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Marvar
authors.affiliation: Division of Behavioral Neuroscience and Psychiatric Disorders, Yerkes National Primate Research Center, Atlanta, GA, USA.|Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Donald
authors.identifier: 0000-0003-0758-0530
authors.initials: D
authors.lastname: Rainnie
authors.affiliation: Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, MA, USA.|Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Kerry J
authors.initials: KJ
authors.lastname: Ressler
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000235:genetics; D000679:Amygdala / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D000075402:Channelrhodopsins; D003214:Conditioning, Classical / Q000502:physiology; D005239:Fear; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007858:Learning / Q000502:physiology*; D008124:Locomotion / Q000235:genetics; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010755:Organophosphates / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D011108:Polymers / Q000378:metabolism; D051745:Protein Kinase C-delta / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000235:genetics / Q000378:metabolism; D018042:Receptors, Neurokinin-3 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*; D015320:Tachykinins / Q000235:genetics* / Q000378:metabolism
chemical_list: D014150:Antipsychotic Agents; D000075402:Channelrhodopsins; D010755:Organophosphates; D010880:Piperidines; D011108:Polymers; D011498:Protein Precursors; D018042:Receptors, Neurokinin-3; D015320:Tachykinins; C044206:preprotachykinin; C542009:tyrosine polyphosphate; D049452:Green Fluorescent Proteins; D051745:Protein Kinase C-delta; D054558:Protein Tyrosine Phosphatases, Non-Receptor; C082101:Ptpn5 protein, mouse; C091554:SR 142801