GHSRs in the olfactory bulb suppress food motivation and promote exploration without altering spatial memory in male mice.

The olfactory bulb (OB) is an emerging neuroendocrine centre regulating appetite, metabolism, and behaviours such as those linked to anxiety, motivation and spatial navigation. These processes are likely mediated by one or more of the many hormone receptors found in the OB. For instance, recent studies show that selective OB deletion of the receptor for ghrelin and LEAP2 (GHSR; growth hormone secretagogue receptor) increases anxiety-like behaviour and impacts peripheral glucose and energy homeostasis. As GHSR function has been linked to motivated behaviours and spatial navigation, we decided to investigate whether OB-selective GHSR (OB^GHSR) deletion affects motivation, using an operant progressive ratio schedule, and/or spatial navigation, using a Y maze and radial arm maze. In contrast to wild-type mice, our study shows that OB^GHSR deletion increased motivated sucrose seeking after a short fast, but not in ad libitum fed mice, and had a mild effect to delay extinction learning. In both Y-maze and radial arm maze studies for spatial navigation, OB^GHSR deletion reduced spatial exploration in terms of distance moved and arm entries. However, the proportion of correct and incorrect arm entries relative to the total number of entries was not affected in either the Y-maze or the radial arm maze, suggesting that spatial memory was not affected. Our study demonstrates that intact OB^GHSRs in male mice normally restrain motivated sucrose seeking in a metabolic state-dependent manner and optimise spatial navigation by increasing exploration, without affecting spatial memory.