The stimulating effect of ghrelin on gastric motility and firing activity of gastric‐distension‐sensitive hippocampal neurons and its underlying regulation by the hypothalamus

Abstract

New Findings r What is the central question of this study?Is there a direct pathway of ghrelin from the hypothalamic arcuate nucleus to the hippocampus? Is this pathway involved in the regulation of gastric motility and gastric afferent signalling? r What is the main finding and its importance?There exists a direct pathway of ghrelin from the hypothalamic arcuate nucleus to the hippocampus that is involved in the regulation of gastric motility. In the emotional hub hippocampus, ghrelin is involved in the regulation of gastric motility and gastric afferent signalling. These effects can be regulated by the hypothalamic arcuate nucleus. This supports and advances the theory of energy balance involving the regulation of the central and brain-gut peptides.Ghrelin is an acylated peptide originally identified in the rat stomach as the endogenous ligand for growth hormone secretagogue receptor (GHSR) that promotes gastric motility. Our aims were to explore the effects of ghrelin on gastric-distension-sensitive neurons in the hippocampus and the potential for ghrelin to regulate gastric motility through the arcuate nucleus (Arc). Single-unit discharges in the hippocampus were recorded extracellularly, and gastric motility in conscious rats was monitored. The expression of GHSR-1a in the hippocampus was determined by PCR, Western blot and fluo-immunohistochemistry staining. Retrograde tracing and fluoimmunohistochemistry staining were used to determine ghrelin neuron projection. GhrelinFluoro-Gold double-labelled neurons and GHSR-1a expression were observed in the Arc and hippocampus, respectively. There were gastric-distension-sensitive neurons in the hippocampus that could be excited by ghrelin or by electrical stimulation of the Arc. The excitatory effects could be blocked completely or partly by pretreatment with the ghrelin receptor antagonist [d-Lys-3]-GHRP-6. Gastric motility was significantly promoted by the administration of ghrelin into the hippocampus in a dose-dependent manner that could be completely abolished by [d-Lys-3]-GHRP-6. Electrical stimulation of the Arc could promote gastric motility as well. Nevertheless, these effects could be mitigated by pretreatment with [d-Lys-3]-GHRP-6. Electrical lesioning of the hippocampus diminished the excitatory effects on gastric motility that were induced by electrical stimulation the Arc. Our findings suggest that ghrelin plays an important role in

Postmeal Optogenetic Inhibition of Dorsal or Ventral Hippocampal Pyramidal Neurons Increases Future Intake

“…As ingestion-related memories contain both mnemonic components, it seems likely that both regions contribute to the memory of a meal. Moreover, both dHC and vHC neurons are anatomically positioned to form a memory of a meal because they express high concentrations of receptors for virtually every food-related signal (Lathe, 2001; Kanoski and Grill, 2015), receive neural impulses regarding energy status (e.g., taste, stomach distention; Xu et al, 2008, 2014), and project to most brain areas critical for energy regulation (Risold and Swanson, 1996; Kishi et al, 2000; Cenquizca and Swanson, 2006; Xu et al, 2014; Hsu et al, 2015b).…”

Sucrose ingestion induces glutamate AMPA receptor phosphorylation in dorsal hippocampal neurons: Increased sucrose experience prevents this effect

“…dHC neurons are critical for the cognitive processes associated with the hippocampus, namely episodic and spatial memory [10–17]. dHC neurons are anatomically poised to form a memory of a meal and control eating behavior because they receive ingestion-related neural signals from several brain regions (reviewed in [18]), express a multitude of receptors for pre- and postprandial signals (e.g., leptin [19,20], insulin [21], ghrelin [22], and melanocortins [23–25]), and project to many brain areas critical for energy regulation [26–29]. We discovered that muscimol-induced inactivation of dHC neurons after the completion of a sucrose meal when the memory of the meal would be undergoing consolidation accelerated the onset of the next meal and increased intake during that meal [30].…”

Ghrelin: Ghrelin as a Regulatory Peptide in Growth Hormone Secretion

“…As revealed by quantitative analysis of doublelabelled cells, the GHS-R are expressed in about one fourth of GHRH mRNA containing neurons in arcuate (ARC) and ventromedial nucleus (VMN) of the hypothalamus thereby suggesting that ghrelin may influence GH secretion through interaction with the GHS-R and that the release of GHRH into hypophyseal portal blood may also be influenced by ghrelin. There is a dual action of GHS and ghrelin on the hypothalamus [9]. They act by increasing the electrical activity and c-fos expression in a subpopulation of some of the GHRHproducing neurons cells in the arcuate nucleus [39].…”

“…The ghrelin receptor (GHS-R1a) is conserved across different vertebrate species of mammals, birds and fishes [5][6][7]. Transcripts for GHSR 1A are expressed at low levels in many tissues, but mostly in the arcuate and ventromedial nuclei of the hypothalamus, pituitary hippocampus and gastrointestinal tract [8,9].…”