Molecular characterization of Thy1 expressing fear-inhibiting neurons within the basolateral amygdala
العنوان: | Molecular characterization of Thy1 expressing fear-inhibiting neurons within the basolateral amygdala |
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المؤلفون: | Jordan Walton, Jidong Guo, Kerry J. Ressler, Kenneth M. McCullough, Dennis C. Choi, Donald G. Rainnie, Kelsey Zimmerman |
المصدر: | Nature Communications Nature Communications, Vol 7, Iss 1, Pp 1-13 (2016) |
سنة النشر: | 2015 |
مصطلحات موضوعية: | 0301 basic medicine, General Physics and Astronomy, Bioinformatics, Extinction, Psychological, Stereotaxic Techniques, Mice, 0302 clinical medicine, Piperidines, Genes, Reporter, Receptors, Neurotensin, Clozapine, education.field_of_study, Multidisciplinary, Basolateral Nuclear Complex, Chemogenetics, Fear, medicine.anatomical_structure, Intercellular Signaling Peptides and Proteins, Oligopeptides, Neurotensin receptor 2, Sensory Receptor Cells, Science, Population, Prefrontal Cortex, Optogenetics, Biology, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Bacterial Proteins, Memory, medicine, Animals, education, Adaptor Proteins, Signal Transducing, Injections, Intraventricular, Integrases, Sequence Analysis, RNA, RNA, General Chemistry, Wnt Proteins, Luminescent Proteins, 030104 developmental biology, nervous system, Gene Expression Regulation, Stereotaxic technique, Thy-1 Antigens, Neuron, Thrombospondins, Neuroscience, 030217 neurology & neurosurgery, Basolateral amygdala |
الوصف: | 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. Activation of Thy-1 expressing neurons in the basolateral amygdala (BLA) has been shown to result in inhibition of fear. Here the authors present a comprehensive workflow to identify genes that are upregulated in this population and can be pharmacologically targeted to enable fear extinction. |
تدمد: | 2041-1723 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6b5410a99cb697ba441fd455c417c204 https://pubmed.ncbi.nlm.nih.gov/27767183 |
حقوق: | OPEN |
رقم الأكسشن: | edsair.doi.dedup.....6b5410a99cb697ba441fd455c417c204 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 20411723 |
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