Ghrelin: A link between memory and ingestive behavior

Abstract

Feeding is a highly complex behavior that is influenced by learned associations between external and internal cues. The type of excessive feeding behavior contributing to obesity onset and metabolic deficit may be based, in part, on conditioned appetitive and ingestive behaviors that occur in response to environmental and/or interoceptive cues associated with palatable food. Therefore, there is a critical need to understand the neurobiology underlying learned aspects of feeding behavior. The stomach-derived “hunger” hormone, ghrelin, stimulates appetite and food intake and may function as an important biological substrate linking mnemonic processes with feeding control. The current review highlights data supporting a role for ghrelin in mediating the cognitive and neurobiological mechanisms that underlie conditioned feeding behavior. We discuss the role of learning and memory on food intake control (with a particular focus on hippocampal-dependent memory processes) and provide an overview of conditioned cephalic endocrine responses. A neurobiological framework is provided through which conditioned cephalic ghrelin secretion signals in neurons in the hippocampus, which then engage orexigenic neural circuitry in the lateral hypothalamus to express learned feeding behavior.

Ventral hippocampal neurons inhibit postprandial energy intake

“…Although our results indicate that vHC neurons influence intake during the postprandial period, it is likely that these neurons also influence intake during the period prior to meal initiation. This possibility is supported by findings showing that the hormone ghrelin, which is released prior to intake and is considered an anticipatory signal for meal initiation (Hsu et al, ), increases intake when infused into vHC (Kanoski et al, ). Moreover, blockade of vHC ghrelin receptors decreases intake of an anticipated meal (Hsu et al, ).…”

Integration of homeostatic signaling and food reward processing in the human brain

“…Furthermore, in ghrelin receptor-deficient mice, cue potentiated feeding is disrupted and meal anticipatory behavior is reduced (63,64), highlighting the importance of ghrelin signaling for feeding driven by external food-related cues (65), which has also been observed in individuals with obesity (39). Since ghrelin influenced brain reward processing in the sated state, our results add to the notion of ghrelin as an important contributor to hedonic eating where food is consumed due to its rewarding properties and not to maintain energy homeostasis (38).…”

Ghrelin enhances food odor conditioning in healthy humans: an fMRI study

“…Both phenomena depend on ghrelin signaling in the hippocampus. For example, ghrelin, as a meal anticipatory signal, has been shown to promote cuedriven feeding via actions on the hippocampus (Hsu et al, 2016), and GHSR blockade prevents cuepotentiated feeding (Walker et al, 2012). In animals trained on a fixed meal schedule, hippocampal GHSR blockade reduces food consumption at the anticipated mealtimes (Hsu et al, 2015), presumably by decoupling the temporal context from cue reactivity.…”

“…There is also a high concentration of GHSR in the hippocampus, where ghrelin can increase spine density and improve learning and memory, possibly by modulating dopamine signaling (Diano et al, 2006;Li et al, 2013;Ribeiro et al, 2014). Conditioned feeding, which occurs in response to learned food-cue associations, is increased in rats upon ghrelin injection into the ventral hippocampus (Hsu et al, 2016;Kanoski et al, 2013). To date, the influence of ghrelin on food-related conditioning has only been tested in animals.…”