Sequential appetite suppression by oral and visceral feedback to the brainstem

Truong Ly, Jun Y. Oh, Nilla Sivakumar, Sarah Shehata, Naymalis La Santa Medina, Heidi Huang, Zhengya Liu, Wendy Fang, Chris Barnes, Naz Dundar, Brooke C. Jarvie, Anagh Ravi, Olivia K. Barnhill, Chelsea Li, Grace R. Lee, Jaewon Choi, Heeun Jang and Zachary A. Knight ()
Additional contact information
Truong Ly: University of California, San Francisco
Jun Y. Oh: University of California, San Francisco
Nilla Sivakumar: University of California, San Francisco
Sarah Shehata: University of California, San Francisco
Naymalis La Santa Medina: University of California, San Francisco
Heidi Huang: University of California, San Francisco
Zhengya Liu: University of California, San Francisco
Wendy Fang: University of California, San Francisco
Chris Barnes: University of California, San Francisco
Naz Dundar: University of California, San Francisco
Brooke C. Jarvie: University of California, San Francisco
Anagh Ravi: University of California, San Francisco
Olivia K. Barnhill: University of California, San Francisco
Chelsea Li: University of California, San Francisco
Grace R. Lee: University of California, San Francisco
Jaewon Choi: University of California, San Francisco
Heeun Jang: University of California, San Francisco
Zachary A. Knight: University of California, San Francisco

Nature, 2023, vol. 624, issue 7990, 130-137

Abstract: Abstract The termination of a meal is controlled by dedicated neural circuits in the caudal brainstem. A key challenge is to understand how these circuits transform the sensory signals generated during feeding into dynamic control of behaviour. The caudal nucleus of the solitary tract (cNTS) is the first site in the brain where many meal-related signals are sensed and integrated1–4, but how the cNTS processes ingestive feedback during behaviour is unknown. Here we describe how prolactin-releasing hormone (PRLH) and GCG neurons, two principal cNTS cell types that promote non-aversive satiety, are regulated during ingestion. PRLH neurons showed sustained activation by visceral feedback when nutrients were infused into the stomach, but these sustained responses were substantially reduced during oral consumption. Instead, PRLH neurons shifted to a phasic activity pattern that was time-locked to ingestion and linked to the taste of food. Optogenetic manipulations revealed that PRLH neurons control the duration of seconds-timescale feeding bursts, revealing a mechanism by which orosensory signals feed back to restrain the pace of ingestion. By contrast, GCG neurons were activated by mechanical feedback from the gut, tracked the amount of food consumed and promoted satiety that lasted for tens of minutes. These findings reveal that sequential negative feedback signals from the mouth and gut engage distinct circuits in the caudal brainstem, which in turn control elements of feeding behaviour operating on short and long timescales.

Date: 2023
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DOI: 10.1038/s41586-023-06758-2

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