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Tripartite extended amygdala–basal ganglia CRH circuit drives locomotor activation and avoidance behavior

Science Advances

Authors: Simon Chang, Federica Fermani, Chu-Lan Lao, Lianyun Huang, Mira Jakovcevski, Rosella Di Giaimo, Miriam Gagliardi, Danusa Menegaz, Alexandru Adrian Hennrich, Michael Ziller, Matthias Eder, Rüdiger Klein, Na Cai, and Jan M. Deussing
Publication: Science Advances
Date: November 16, 2022
Link to article: https://doi.org/10.1126/sciadv.abo1023


An adaptive stress response involves various mediators and circuits orchestrating a complex interplay of physiological, emotional, and behavioral 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 hyperactivation of the hypothalamic-pituitary-adrenal axis, locomotor activation, and avoidance behavior contingent on CRH receptor type 1 (CRHR1) located at axon terminals in the SN, which originate from external globus pallidus (GPe) neurons. The neuronal activity prompting the observed behavior is shaped by IPACLCRH and GPeCRHR1 neurons coalescing in the SN. These results delineate a previously unidentified tripartite CRH circuit functionally connecting extended amygdala and basal ganglia nuclei to drive locomotor activation and avoidance behavior.

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