Modulation of innate fear by CART neuropeptide

Abstract

CART (Cocaine- and amphetamine-regulated transcript) is a key neuropeptide involved in regulating various processes like food intake and energy homeostasis, reward and addiction, and learning and memory. Studies have also implicated CART in anxiety and fear, behaviours associated with defensive survival circuits. Extensive CART involvement in various processes utilizing different conserved circuits implicates CART as a potential candidate for neuropeptide-mediated crosstalk between survival circuits. The role of CART in the interactions between threat defense and feeding circuits was studied by employing CART knockout animals and analyzing the innate fear and anxiety-like responses under different energy states. Our studies further CART as a crosstalk-mediating neuropeptide as the behavioral variations observed under the different energy states were exhibited exclusively in animals capable of CART expression. Additionally, chronic depletion of CART appears to sensitize the CART system, thereby counteracting the reduction in CART levels and enabling participation in the subsequent functions of fear and anxiety processing. The central nucleus of the amygdala (CeA) is a critical region involved in anxiety and fear that comprises and receives extensive CART-expressing neurons. Potential innervation of CART neurons from the arcuate nucleus of the hypothalamus, a key food intake regulator, to the CeA, implicates CeA as an integrative site for feeding and threat circuits, and studies to elucidate the neural mechanisms involved are underway.