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  • Cellular coding of ingestion in the caudal brainstem. bioRxiv : the preprint server for biology Ly, T., Yi, X., Lee, G. R., Grove, J. C., Sibih, Y. E., Oh, J. Y., Qiu, L., Sivakumar, N., Knight, Z. A. 2026

    Abstract

    The passage of food through the alimentary canal generates a series of feedback signals that are sensed by the brain and used to control behavior. Many of these signals converge on the caudal nucleus of the solitary tract (cNTS), a brainstem structure that is the direct target of the vagal sensory neurons that innervate the throat, stomach and intestines1-4 and detect ingested food5-8. These vagal neurons are thought to transmit key gut-brain signals that trigger meal termination9-14, but how this information is represented in the cNTS, and used to control behavior, is largely unknown. Here, we have used a preparation for single-cell imaging in the cNTS of behaving animals15 to characterize how food ingestion is encoded in the caudal brainstem. We find that when food is delivered directly to the stomach, thereby bypassing the oral cavity, cNTS neurons exhibit ramping activation that occurs over many minutes and depends on canonical gut-brain pathways. However, when the same food is consumed by mouth, most cNTS neurons exhibit phasic, seconds-timescale responses that are time-locked to oral contact of food or cues that predict food delivery. We show that this rapid feedback is due to a combination of mechanical, gustatory and nutritive signals from the mouth and throat and does not require canonical gut-brain pathways, including gut-innervating vagal afferents, although GI feedback modulates the duration of these pregastric responses. We show that one source of this rapid input is descending projections from the paraventricular hypothalamus, which track ingestion dynamics and are required for proper meal termination. These findings reveal that the caudal brainstem makes extensive use of pregastric signals that track the dynamics of ingestion for the rapid control of food consumption.

    View details for DOI 10.64898/2025.11.30.691333

    View details for PubMedID 41542647

    View details for PubMedCentralID PMC12802400