CART in Modulating Memory and Risk-taking Behaviours

Abstract

Evolution demanded not only the acute ability to detect and respond to threats but also the capability to learn from these encounters. The interactions between survival circuits and energy states in the brain, including those that are less relevant to immediate survival needs, can vary depending on the energy state of the organism. CART (cocaine and amphetamine-regulated transcript) is a neuropeptide that is mainly studied in the context of appetite regulation and energy homeostasis; it is anorexic in nature. CART is robustly expressed in hypothalamic regions, which are key regulators of food intake and energy balance, such as the arcuate nucleus (Arc), paraventricular nucleus, dorsomedial nucleus, and ventromedial nucleus. It is also found in the limbic system, including the central amygdala (CeA), ventral bed nucleus of stria terminalis (vBNST); which play important roles in emotional responses, and the hippocampal regions; modulating higher cognitive functions like learning and memory. Here, we show that CART plays a role in learning and memory formation in mice using Novel object recognition test (NOR) as CART-/- mice show recognition memory impairment. Additionally, we also show that fasting has no effect on recognition memory in NOR before training and before testing. Further, we investigated the role of CART in energy state-dependent adaptive prioritisation of behaviours by optimising multiple behavioural paradigms assessing risk-taking behaviours along with chemogenetics to selectively modulate the activity of ArcCART neurons in dissecting out the role energy states have on different survival circuits.