Maintaining energy balance is of paramount importance for metabolic health and survival. It is achieved through the coordinated regulation of neuronal circuits that control a wide range of physiological processes affecting energy intake and expenditure, such as feeding, metabolic rate, locomotor activity, arousal, growth and reproduction. Neuronal populations distributed throughout the CNS but highly enriched in the mediobasal hypothalamus, sense hormonal, nutrient and neuronal signals of systemic energy status and relay this information to secondary neurons that integrate the information and regulate distinct physiological parameters in a manner that promotes energy homeostasis. To achieve this, it is critical that neuronal circuits provide information about short-term changes in nutrient availability in the larger context of long-term energy status. For example, the same signals lead to different cellular and physiological responses if delivered under fasted versus fed conditions. Thus, there is a clear need to have mechanisms that rapidly and reversibly adjust responsiveness of hypothalamic circuits to acute changes in nutrient availability.