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

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Listed:
  • Kenneth M. McCullough

    (Behavioral Neuroscience, Emory University
    McLean Hospital, Belmont
    Harvard Medical School, Boston)

  • 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
    McLean Hospital, Belmont
    Harvard Medical School, Boston)

  • Donald G. Rainnie

    (Behavioral Neuroscience, Emory University)

  • Kerry J. Ressler

    (Behavioral Neuroscience, Emory University
    McLean Hospital, Belmont
    Harvard Medical School, Boston)

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.

Suggested Citation

  • Kenneth M. McCullough & Dennis Choi & Jidong Guo & Kelsey Zimmerman & Jordan Walton & Donald G. Rainnie & Kerry J. Ressler, 2016. "Molecular characterization of Thy1 expressing fear-inhibiting neurons within the basolateral amygdala," Nature Communications, Nature, vol. 7(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13149
    DOI: 10.1038/ncomms13149
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