Paper Title
Dreadd-Mediated Stimulation of Ghsr-Expressing Cells in Telencephalon Differentially Impacts Feeding Behavior

Abstract
The gastric hunger signal, ghrelin, influences feeding behavior via activation of the growth hormone secretagogue receptor (GHSR). GHSR’s are expressed in multiple brain regions, in particular thebasolateral ventral hippocampus. This region plays a critical role in the initiation and overall amount of feeding behaviors. In this study, we used a GHSR-IRES-Cre mouse line that expresses Cre directed by the GHSR promoter. Mice received Cre-dependent excitatory DREADDinto the VHPC to examine whether chemogenetic stimulation of GHSR-expressing cells within these regions would influence consumption of lab chow or a palatable high fat diet (HFD). On test days, mice were injected with clozapine-N-oxide (CNO) or vehicle solution prior to the onset of the dark cycleand given portioned access to either lab chow or HFD. CNO-evoked DREADD stimulation VHPCGHSR-expressing cells significantly enhanced lab chow but not HFD intake. To examine intake of specific macronutrients and the nature of any changes in ingestive behavior, we separately investigated fluid intake of lipid (45% corn oil), sugar (20% sucrose), and starch (20% maltodextrin) through an analysis of licking microstructure. This quantitativeapproach is capable of dissociatingoverall intake into individual components of pre-ingestive (e.g.,orosensory, palatability; via burst size) and post-ingestive (e.g., negative feedback; via burst number) variables that regulate meal intake. The chemogenetic manipulations mainly influenced short-term solution intake in VHPC mice, such that excitation of GHSR-expressing cells in this region surprisingly inhibited sucrose intake through a decrease in burst number. Conversely, DREADD activation of these cells increased the palatability of corn oil. These data provide insight into the differential role of central nervous system GHSR-expressing cells on ingestive behavior that is in partdependent on the neuronal loci in which they are expressed and the nature of the tastant being consumed. Keywords - Ghrelin, Feeding, Hippocampus, Obesity.