TY - JOUR T1 - Hypothalamic-Extended Amygdala Circuit Regulates Temporal Discounting JF - The Journal of Neuroscience JO - J. Neurosci. SP - 1928 LP - 1940 DO - 10.1523/JNEUROSCI.1836-20.2020 VL - 41 IS - 9 AU - Haofang E. Li AU - Mark A. Rossi AU - Glenn D.R. Watson AU - H. Gregory Moore AU - Min Tong Cai AU - Namsoo Kim AU - Katrina A. Vokt AU - Dongye Lu AU - Ryan A. Bartholomew AU - Ryan N. Hughes AU - Henry H. Yin Y1 - 2021/03/03 UR - http://www.jneurosci.org/content/41/9/1928.abstract N2 - Choice behavior is characterized by temporal discounting, i.e., preference for immediate rewards given a choice between immediate and delayed rewards. Agouti-related peptide (AgRP)-expressing neurons located in the arcuate nucleus of the hypothalamus (ARC) regulate food intake and energy homeostasis, yet whether AgRP neurons influence choice behavior and temporal discounting is unknown. Here, we demonstrate that motivational state potently modulates temporal discounting. Hungry mice (both male and female) strongly preferred immediate food rewards, yet sated mice were largely indifferent to reward delay. More importantly, selective optogenetic activation of AgRP-expressing neurons or their axon terminals within the posterior bed nucleus of stria terminalis (BNST) produced temporal discounting in sated mice. Furthermore, activation of neuropeptide Y (NPY) type 1 receptors (Y1Rs) within the BNST is sufficient to produce temporal discounting. These results demonstrate a profound influence of hypothalamic signaling on temporal discounting for food rewards and reveal a novel circuit that determine choice behavior.SIGNIFICANCE STATEMENT Temporal discounting is a universal phenomenon found in many species, yet the underlying neurocircuit mechanisms are still poorly understood. Our results revealed a novel neural pathway from agouti-related peptide (AgRP) neurons in the hypothalamus to the bed nucleus of stria terminalis (BNST) that regulates temporal discounting in decision-making. ER -