Reconsolidation of a post-ingestive nutrient memory requires mTOR in the central amygdala

Abstract

The central control of feeding behavior and metabolic homeostasis has been proposed to involve a form of post-ingestive nutrient learning independent of the gustatory value of food. However, after such learning, it is unknown which brain regions or circuits are activated to retrieve the stored memory and whether this memory undergoes reconsolidation that depends on protein synthesis after its reactivation through retrieval. In the present study, using a conditioned-flavor-preference paradigm by associating flavors with intra-gastric infusion of glucose to minimize the evaluation of the taste of food, we show that retrieval of the post-ingestive nutrient-conditioned flavor memory stimulates multiple brain regions in mice, including the central nucleus of the amygdala (CeA). Moreover, memory retrieval activated the mammalian target of rapamycin complex 1 (mTORC1) in the CeA, while site-specific or systemic inhibition of mTORC1 immediately after retrieval prevented the subsequent expression of the post-ingestive nutrient-associated flavor memory, leading to a long-lasting suppression of reinstatement. Taken together, our findings suggest that the reconsolidation process of a post-ingestive nutrient memory modulates food preferences.

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Fig. 1: CFP memory retrieval recruits distributed circuits including the amygdala, lateral septum, and nucleus accumbens.
Fig. 2: Effects of rapamycin on CeA mTORC1 activity and reconsolidation of CFP memory.
Fig. 3: Systemic mTORC1 inhibition disrupts reconsolidation of CFP memory.
Fig. 4: mTORC1 inhibition in the CeA fails to affect CFP memory without reactivation.
Fig. 5: mTORC1 inhibition in the CeA fails to affect CFP memory at 6 h after reactivation.
Fig. 6: mTORC1 inhibition in the CeA after reactivation prevents relapse.

Data availability

All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Additional data available from authors upon request.

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Acknowledgements

We thank Shanghai Institute of Pediatric Translational Medicine, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine for providing us with experimental facility to this work. This study was supported by grants from the National Natural Science Foundation of China (81761128035, 81771214, 81930095, 81701334 and 81703249), the Science and Technology Commission of Shanghai Municipality (17XD1403200, 18DZ2313505, 18QA1402500, and 19410713500), the Shanghai Municipal Education Commission (Research Physician Project: 20152234), the Shanghai Municipal Health Commission (2017ZZ02026, 2017EKHWYX-02, 2018BR33, and 2020CXJQ01), the Shanghai Shen Kang Hospital Development Center (16CR2025B), the Shanghai Municipal Science and Technology Major Project (2018SHZDZX01), the Guangdong Key Project in “Development of new tools for diagnosis and treatment of Autism” (2018B030335001), the National Human Genetic Resources Sharing Service Platform (2005DKA21300), the Shanghai Clinical Key Subject Construction Project (shslczdzk02902), Xinhua Hospital Affiliated Shanghai Jiao Tong University School of Medicine (2018YJRC03), and innovative research team of high-level local universities in Shanghai.

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Yan, Y., Zhang, L., Zhu, T. et al. Reconsolidation of a post-ingestive nutrient memory requires mTOR in the central amygdala. Mol Psychiatry (2020). https://doi.org/10.1038/s41380-020-00874-5

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