title: Molecular characterization of Thy1 expressing fear-inhibiting neurons within the basolateral amygdala.
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.
authors: Behavioral Neuroscience, Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, Georgia 30322, USA.|Division of Depression &Anxiety Disorders, McLean Hospital, Belmont, Massachusetts 02478, USA.|Department of Psychiatry, Harvard Medical School, Boston, Massachusetts 02478, USA.
authors: Kenneth M
authors: KM
authors: McCullough
authors: Behavioral Neuroscience, Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, Georgia 30322, USA.
authors: Dennis
authors: D
authors: Choi
authors: Behavioral Neuroscience, Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, Georgia 30322, USA.
authors: Jidong
authors: J
authors: Guo
authors: School of Psychology, University of New South Wales, Sydney, New South Wales 2052, Australia.
authors: Kelsey
authors: K
authors: Zimmerman
authors: Behavioral Neuroscience, Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, Georgia 30322, USA.|Division of Depression &Anxiety Disorders, McLean Hospital, Belmont, Massachusetts 02478, USA.|Department of Psychiatry, Harvard Medical School, Boston, Massachusetts 02478, USA.
authors: Jordan
authors: J
authors: Walton
authors: Behavioral Neuroscience, Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, Georgia 30322, USA.
authors: Donald G
authors: 0000-0003-0758-0530
authors: DG
authors: Rainnie
authors: Behavioral Neuroscience, Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, Georgia 30322, USA.|Division of Depression &Anxiety Disorders, McLean Hospital, Belmont, Massachusetts 02478, USA.|Department of Psychiatry, Harvard Medical School, Boston, Massachusetts 02478, USA.
authors: Kerry J
authors: KJ
authors: Ressler
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D066272:Basolateral Nuclear Complex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D003024:Clozapine / Q000031:analogs & derivatives / Q000494:pharmacology; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology*; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D007276:Injections, Intraventricular; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D009842:Oligopeptides / Q000494:pharmacology; D062308:Optogenetics / Q000379:methods; D010880:Piperidines / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018028:Receptors, Neurotensin / Q000235:genetics / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017423:Sequence Analysis, RNA; D013238:Stereotaxic Techniques; D019699:Thrombospondins / Q000235:genetics / Q000378:metabolism; D018800:Thy-1 Antigens / Q000235:genetics* / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D000098907:R-Spondins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D001426:Bacterial Proteins; D003024:Clozapine; D019426:Integrases; D036341:Intercellular Signaling Peptides and Proteins; D008164:Luminescent Proteins; D009842:Oligopeptides; D010880:Piperidines; D018028:Receptors, Neurotensin; D019699:Thrombospondins; D018800:Thy-1 Antigens; D051153:Wnt Proteins; C405061:Dkk3 protein, mouse; C490984:Ntsr2 protein, mouse; C518904:RSPO2 protein, mouse; D000098907:R-Spondins; C490508:Wnt7a protein, mouse; C102984:beta-lactotensin; C054562:yellow fluorescent protein, Bacteria; C045073:Cre recombinase; C047340:levocabastine; C079149:clozapine N-oxide