TY - JOUR T1 - Kappa opioid receptor-dynorphin signaling in the central amygdala regulates conditioned threat discrimination and anxiety JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0370-20.2020 SP - ENEURO.0370-20.2020 AU - Madison A. Baird AU - TingTing Y. Hsu AU - Rachel Wang AU - Barbara Juarez AU - Larry S. Zweifel Y1 - 2020/12/14 UR - http://www.eneuro.org/content/early/2020/12/10/ENEURO.0370-20.2020.abstract N2 - Neuropeptides within the central nucleus of the amygdala (CeA) potently modulate neuronal excitability and have been shown to regulate conditioned threat discrimination and anxiety. Here, we investigated the role of kappa opioid receptor (KOR) and its endogenous ligand dynorphin in the CeA for regulation of conditioned threat discrimination and anxiety-like behavior in mice. We demonstrate that reduced KOR expression through genetic inactivation of the KOR encoding gene, Oprk1, in the CeA results in increased anxiety-like behavior and impaired conditioned threat discrimination. In contrast, reduction of dynorphin through genetic inactivation of the dynorphin encoding gene, Pdyn, in the CeA has no effect on anxiety or conditioned threat discrimination. However, inactivation of Pdyn from multiple sources, intrinsic and extrinsic to the CeA phenocopies Oprk1 inactivation. These findings suggest that dynorphin inputs to the CeA signal through KOR to promote threat discrimination and dampen anxiety.Significance Statement The regulation of fear and anxiety-related behavior are critically dependent on the central nucleus of the amygdala region of the brain. Here, we demonstrate that signaling through the kappa opioid receptor in the central nucleus of the amygdala regulates conditioned threat discrimination and anxiety related behavior mice. These findings have broad implications for the neural mechanisms that regulate conditioned threat and anxiety-related behavior. ER -