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

Kenneth M. McCullough, Dennis Choi, Jidong Guo, Kelsey Zimmerman, Jordan Walton, Donald G. Rainnie and Kerry J. Ressler ()
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Kenneth M. McCullough: Behavioral Neuroscience, Emory University
Dennis Choi: Behavioral Neuroscience, Emory University
Jidong Guo: Behavioral Neuroscience, Emory University
Kelsey Zimmerman: School of Psychology, University of New South Wales
Jordan Walton: Behavioral Neuroscience, Emory University
Donald G. Rainnie: Behavioral Neuroscience, Emory University
Kerry J. Ressler: Behavioral Neuroscience, Emory University

Nature Communications, 2016, vol. 7, issue 1, 1-13

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms13149

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