Journal article
A neural mechanism for learning from delayed postingestive feedback
Nature (London), Vol.642(8068), pp.700-709
06/19/2025
DOI: 10.1038/s41586-025-08828-z
PMCID: PMC12176619
PMID: 40175547
Abstract
Animals learn the value of foods on the basis of their postingestive effects and thereby develop aversions to foods that are toxic(1, 2, 3, 4, 5, 6, 7, 8, 9-10) and preferences to those that are nutritious(11, 12-13). However, it remains unclear how the brain is able to assign credit to flavours experienced during a meal with postingestive feedback signals that can arise after a substantial delay. Here we reveal an unexpected role for the postingestive reactivation of neural flavour representations in this temporal credit-assignment process. To begin, we leverage the fact that mice learn to associate novel(14,15), but not familiar, flavours with delayed gastrointestinal malaise signals to investigate how the brain represents flavours that support aversive postingestive learning. Analyses of brain-wide activation patterns reveal that a network of amygdala regions is unique in being preferentially activated by novel flavours across every stage of learning (consumption, delayed malaise and memory retrieval). By combining high-density recordings in the amygdala with optogenetic stimulation of malaise-coding hindbrain neurons, we show that delayed malaise signals selectively reactivate flavour representations in the amygdala from a recent meal. The degree of malaise-driven reactivation of individual neurons predicts the strengthening of flavour responses upon memory retrieval, which in turn leads to stabilization of the population-level representation of the recently consumed flavour. By contrast, flavour representations in the amygdala degrade in the absence of unexpected postingestive consequences. Thus, we demonstrate that postingestive reactivation and plasticity of neural flavour representations may support learning from delayed feedback.
Details
- Title: Subtitle
- A neural mechanism for learning from delayed postingestive feedback
- Creators
- Christopher A. Zimmerman - Princeton UniversityScott S. Bolkan - Princeton UniversityAlejandro Pan-Vazquez - Princeton UniversityBichan Wu - Princeton UniversityEmma F. Keppler - Princeton UniversityJordan B. Meares-Garcia - Princeton UniversityEartha Mae Guthman - Princeton UniversityRobert N. Fetcho - Princeton UniversityBrenna McMannon - Princeton UniversityJunuk Lee - Princeton UniversityAustin T. Hoag - Princeton UniversityLaura A. Lynch - Princeton UniversitySanjeev R. Janarthanan - Princeton UniversityJuan F. Lopez Luna - Princeton UniversityAdrian G. Bondy - Princeton UniversityAnnegret L. Falkner - Princeton UniversitySamuel S. -H. Wang - Princeton UniversityIlana B. Witten - Princeton University
- Resource Type
- Journal article
- Publication Details
- Nature (London), Vol.642(8068), pp.700-709
- DOI
- 10.1038/s41586-025-08828-z
- PMID
- 40175547
- PMCID
- PMC12176619
- NLM abbreviation
- Nature
- ISSN
- 0028-0836
- eISSN
- 1476-4687
- Publisher
- NATURE PORTFOLIO
- Number of pages
- 38
- Grant note
- K99-DA059957; P50-MH136296; U19-NS123716; DP1-MH136573; U19-NS104648; RF1-MH128776 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Brain Research Foundation Helen Hay Whitney Foundation Howard Hughes Medical Institute Simons Collaboration on the Global Brain
- Language
- English
- Date published
- 06/19/2025
- Academic Unit
- Psychological and Brain Sciences
- Record Identifier
- 9984944741002771
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