Ghrelin infusion into the basolateral amygdala suppresses CTA memory formation in rats via the PI3K/Akt/mTOR and PLC/PKC signaling pathways

Ming Yu1, Qian-qian Zhu1, Ming-lu Niu1, Nan Li1, Bai-qing Ren1, Teng-bo Yu2, Zhi-shang Zhou3, Ji-dong Guo4, Yu Zhou1,5,6
1 Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Qingdao University, Qingdao 266071, China
2 Department of Sports Medicine, Affiliated Hospital of Qingdao University, Qingdao 266000, China
3 Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao 266071, China
4 Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA
5 Department of rehabilitation medicine, Affiliated Hospital of Qingdao University, Qingdao 266000, China
6 Institute of Brain Sciences and Related Disorders, Qingdao University, Qingdao 266071, China
Correspondence to: Teng-bo Yu:, Yu Zhou:,
DOI: 10.1038/s41401-022-00859-w
Received: 1 November 2021
Accepted: 3 January 2022
Advance online: 15 February 2022


Ghrelin is a circulating orexigenic hormone that promotes feeding behavior and regulates metabolism in humans and rodents. We previously reported that local infusion of ghrelin into the basolateral amygdala (BLA) blocked memory acquisition for conditioned taste aversion (CTA) by activating growth hormone secretagogue receptor 1a. In this study, we further explored the underlying mechanism and signaling pathways mediating ghrelin modulation of CTA memory in rats. Pharmacological agents targeting distinct signaling pathways were infused into the BLA during conditioning. We showed that preadministration of the PI3K inhibitor LY294002 abolished the repressive effect of ghrelin on CTA memory. Moreover, LY294002 pretreatment prevented ghrelin from inhibiting Arc and zif268 mRNA expression in the BLA triggered by CTA memory retrieval. Preadministration of rapamycin eliminated the repressive effect of ghrelin, while Gsk3 inhibitors failed to mimic ghrelin’s effect. In addition, PLC and PKC inhibitors microinfused in the BLA blocked ghrelin’s repression of CTA acquisition. These results demonstrate that ghrelin signaling in the BLA shapes CTA memory via the PI3K/Akt/mTOR and PLC/PKC pathways. We conducted in vivo multichannel recordings from mouse BLA neurons and found that microinjection of ghrelin (20 μM) suppressed intrinsic excitability. By means of whole-cell recordings from rat brain slices, we showed that bath application of ghrelin (200 nM) had no effect on basal synaptic transmission or synaptic plasticity of BLA pyramidal neurons. Together, this study reveals the mechanism underlying ghrelin-induced interference with CTA memory acquisition in rats, i.e., suppression of intrinsic excitability of BLA principal neurons via the PI3K/Akt/mTOR and PLC/PKC pathways.
Keywords: ghrelin; conditioned taste aversion; basolateral amygdala; memory acquisition; intrinsic excitability; electrophysiology

Article Options

Download Citation

Cited times in Scopus