Ingestion-activated CGRP neurons control learning but not satiety.

Calcitonin Gene-Related Peptide (CGRP) neurons in the parabrachial nucleus are critical for sickness and malaise but have also been proposed to control non-aversive (rewarding) satiation. How one cell type can coordinate these opposing processes has not been explained. Here we reinvestigate the function of these cells using single-cell imaging and optical manipulations. Contrary to current models, we show that CGRP neurons do not track cumulative food consumption, and their activity is not necessary for meal termination or satiety. Instead, we identify two distinct populations of CGRP cells, one of which responds rapidly to appetitive signals during ingestion and the other of which responds slowly to aversive visceral cues. Surprisingly, the ingestion-activated CGRP neurons are important for learning about post-ingestive effects but do not control ongoing food consumption. This reveals two populations of CGRP neurons that are sequentially engaged during, and responsible for, the distinct stages of post-ingestive, aversive learning.