@article{201901,
  author = {Christopher Zimmerman and Alejandro Pan-Vazquez and Bichan Wu and Emma Keppler and Eartha Guthman and Robert Fetcho and Scott Bolkan and Brenna McMannon and Junuk Lee and Austin Hoag and Laura Lynch and Sanjeev Janarthanan and Juan Luna and Adrian Bondy and Annegret Falkner and Samuel Wang and Ilana Witten},
  title = {A neural mechanism for learning from delayed postingestive feedback},
  abstract = {<p>Animals learn the value of foods based on their postingestive effects and thereby develop aversions to foods that are toxic1{\textendash}6 and preferences to those that are nutritious7{\textendash}14. However, it remains unclear how the brain is able to assign credit to flavors experienced during a meal with postingestive feedback signals that can arise after a substantial delay. Here, we reveal an unexpected role for postingestive reactivation of neural flavor representations in this temporal credit assignment process. To begin, we leverage the fact that mice learn to associate novel15{\textendash}18, but not familiar, flavors with delayed gastric malaise signals to investigate how the brain represents flavors that support aversive postingestive learning. Surveying cellular resolution brainwide activation patterns reveals that a network of amygdala regions is unique in being preferentially activated by novel flavors across every stage of the learning process: the initial meal, delayed malaise, and memory retrieval. By combining high-density recordings in the amygdala with optogenetic stimulation of genetically defined hindbrain malaise cells, we find that postingestive malaise signals potently and specifically reactivate amygdalar novel flavor representations from a recent meal. The degree of malaise-driven reactivation of individual neurons predicts strengthening of flavor responses upon memory retrieval, leading to stabilization of the population-level representation of the recently consumed flavor. In contrast, meals without postingestive consequences degrade neural flavor representations as flavors become familiar and safe. Thus, our findings demonstrate that interoceptive reactivation of amygdalar flavor representations provides a neural mechanism to resolve the temporal credit assignment problem inherent to postingestive learning.Competing Interest StatementThe authors have declared no competing interest.</p>},
  year = {2024},
  journal = {bioRxiv},
  publisher = {Cold Spring Harbor Laboratory},
  url = {https://www.biorxiv.org/content/early/2024/01/13/2023.10.06.561214},
  doi = {10.1101/2023.10.06.561214},
}