Molecular characterization of Thy1 expressing fear-inhibiting neurons within the basolateral amygdala

• Type of Material: Article
• Authors: Kenneth M. McCullough, Emory University; Dennis Choi, Emory University; Jidong Guo, Emory University; Kelsey Zimmerman, University of New South Wales; Jordan Walton, Emory University; Donald Rainnie, Emory University; Kerry Ressler, Emory University
• Language: English
• Date: 2016-10-21
• Publisher: Nature Publishing Group: Nature Communications
• Publication Version: Final Published Version
• Copyright Statement: © 2016 The Author(s).
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/ncomms13149
• Title of Journal or Parent Work: Nature Communications
• ISSN: 2041-1723
• Volume: 7
• Start Page: 13149
• End Page: 13149
• Grant/Funding Information: Support was provided by NIH (T32-GM08605, R01MH108665, and R01MH096764) and by an NIH/NCRR base grant (P51RR000165) to Yerkes National Primate Research Center.
• Keywords: REMOTE-CONTROL; NEUROTENSIN RECEPTORS; Science & Technology; TRANSGENIC MICE; CIRCUITS; CONDITIONED FEAR; ADULT; Multidisciplinary Sciences; BETA-LACTOTENSIN; MECHANISMS; Science & Technology - Other Topics; BRAIN; MEMORY
• Research Categories: Biology, Neuroscience; Psychology, Psychobiology

Abstract

Molecular characterization of neuron populations, particularly those controlling threat responses, is essential for understanding the cellular basis of behaviour and identifying pharmacological agents acting selectively on fear-controlling circuitry. Here we demonstrate a comprehensive workflow for identification of pharmacologically tractable markers of behaviourally characterized cell populations. Thy1-eNpHR-, Thy1-Cre-and Thy1-eYFP-labelled neurons of the BLA consistently act as fear inhibiting or 'Fear-Off' neurons during behaviour. We use cell-type-specific optogenetics and chemogenetics (DREADDs) to modulate activity in this population during behaviour to block or enhance fear extinction. Dissociated Thy1-eYFP neurons are isolated using FACS. RNA sequencing identifies genes strongly upregulated in RNA of this population, including Ntsr2, Dkk3, Rspo2 and Wnt7a. Pharmacological manipulation of neurotensin receptor 2 confirms behavioural effects observed in optogenetic and chemogenetic experiments. These experiments identify and validate Ntsr2-expressing neurons within the BLA, as a putative 'Fear-Off' population.