Effect of ghrelin on the regulation of dendritic spines in the rat hippocampus

Ghrelin is a 28‐amino acid orexigenic peptide. Recent evidence suggests ghrelin may promote learning and memory in the hippocampus by increasing the number of synapses on dendritic spines. However, it is not completely understood whether more synapses were expressed on existing spines or additional spines were generated to accomodate newly‐formed synapses. We hypothesized that ghrelin promoted a generation of spines. Cultured hippocampal slices were incubated in 200 nM of ghrelin for 60 min. The slices were fixed, permealized, and processed for visualization of dendritic spines using Alexa 488‐conjugated phalloidin, a mushroom toxin that has a high affinity to F‐actin. Results were quantified using a confocal microscope and IPLab imaging software. Ghrelin increased phalloidin signals. The antagonist of the ghrelin receptor, D‐Lys3‐GHSR‐6, blocked the effect of ghrelin on phallodin signals. This suggested that ghrelin increased the number of dendritic spines, and this effect was mediated by the ghrelin receptor. Our results suggest ghrelin may have a stimulating effect on the generation or remodeling of dendritic spines. Increased number of dendritic spines in hippocampal neurons can accommodate more learning and memories. Thus, ghrelin may be a key molecule for the induction and maintenance of food‐related, appetitive memories. This work is supported by NIH grant 8SC1DA029329 to MI.