The Role of Ghrelin in Regulating Synaptic Function and Plasticity of Feeding-Associated Circuits

Synaptic plasticity of the neuronal circuits associated with feeding behavior is regulated by peripheral signals as a response to changes in the energy status of the body. These signals include glucose, free fatty acids, leptin and ghrelin and are released into circulation, being able to reach the brain. Ghrelin, a small peptide released from the stomach, is an orexigenic hormone produced in peripheral organs, and its action regulates food intake, body weight and glucose homeostasis. Behavioral studies show that ghrelin is implicated in the regulation of both hedonic and homeostatic feeding and of cognition. Ghrelin-induced synaptic plasticity has been described in neuronal circuits associated with these behaviors. In this review, we discuss the neuromodulatory mechanisms induced by ghrelin in regulating synaptic plasticity in three main neuronal circuits previously associated with feeding behaviors, namely hypothalamic (homeostatic feeding), ventral tegmental (hedonic and motivational feeding) and hippocampal (cognitive) circuits. Given the central role of ghrelin in regulating feeding behaviors, and the altered ghrelin levels associated with metabolic disorders such as obesity and anorexia, it is of paramount relevance to understand the effects of ghrelin on synaptic plasticity of neuronal circuits associated with feeding behaviors.