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Tripartite extended amygdala - basal ganglia CRH circuit drives arousal and avoidance behaviour

Simon ChangiD, Federica FermaniiD, Chu Lan LaoiD, Lianyun HuangiD, Mira JakovcevskiiD, Rossella Di GiaimoiD, Miriam GagliardiiD, Danusa MenegaziD, Alexander Adrian Hennrich, Michael J. ZilleriD, Matthias EderiD, Rüdiger KleiniD, Na CaiiD, Jan M. DeussingiD

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Abstract

An adaptive stress response involves various mediators and circuits orchestrating a complex interplay of physiological, emotional and behavioural adjustments. We identified a population of corticotropin-releasing hormone (CRH) neurons in the lateral part of the interstitial nucleus of the anterior commissure (IPACL) - a subdivision of the extended amygdala, which exclusively innervate the substantia nigra (SN). Specific stimulation of this circuit elicits arousal and avoidance behaviour contingent on CRH receptor 1 (CRHR1) located at axon terminals in the SN, which originate from external globus pallidus (GPe) neurons. The neuronal activity prompting the observed behaviour is shaped by IPACLCRH and GPeCRHR1 neurons coalescing in the SN. These results delineate a novel tripartite CRH circuit functionally connecting extended amygdala and basal ganglia nuclei to drive arousal and avoidance behaviour. One-Sentence SummaryBrain centres involved in emotional and motor control are connected through a stress peptide promoting arousal and avoidance behaviour

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