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

Chang, Simon; Fermani, Federica; Lao, Chu-Lan; Huang, Lianyun; Jakovcevski, Mira; Di Giaimo, Rossella; Gagliardi, Miriam; Menegaz, Danusa et al. · Sci Adv · 2022

basic_science · Level V

Where this comes from

Abstract

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 IPACL<sup>CRH</sup> and GPe<sup>CRHR1</sup> 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.