Mice lacking the ghrelin receptor (GHS-R -/-) exhibit impaired hippocampal-dependent learning.

Abstract

Ghrelin is a 28 amino acid peptide produced by epithelial cells in the stomach which increases food intake. Hypothalamic ghrelin receptors are thought to play an important role in the regulation of energy balance. However, ghrelin receptors are also expressed in several extra-hypothalamic brain regions, including the hippocampal formation. Previous work from our lab and others suggest that ghrelin is important for learning and memory. Specifically, intra-hippocampal ghrelin administration increases memory retention in a Step-Down Passive Avoidance test and ghrelin-deficient mice exhibit attenuated performance of the Novel Object Recognition task. In the current study, we utilized ghrelin receptor-deficient mice (GHS-R -/-) to confirm that ghrelin-signaling is necessary for the acquisition of a hippocampal-dependent spatial memory task. Consistent with previous reports, GHS-R -/- mice weigh less and have reduced average food intake relative to wild-type (WT) controls. GHS-R -/- and WT mice ( n 's=8/group) were trained in a Morris water maze task. GHS-R -/- mice exhibited significantly increased escape latencies relative to their WT controls, supporting the conclusion that ghrelin receptor signaling is required for the acquisition of a truly hippocampal-dependent task. Additional studies examine the role of GSH-R in the acquisition of non-hippocampal dependent tasks including learned meal-initiation and conditioned fear. Overall, these data confirm and extend out previous findings that ghrelin is a key mediator of hippocampal-dependent learning processes.