Fig. 6 |. Novel flavor consumption triggers PKA activity in the amygdala, providing a potential biochemical eligibility trace for reactivation by postingestive CGRP neuron activity.

a, Simplified schematic of the biochemical pathway that has been proposed to recruit a subset of amygdala neurons into the CTA memory retrieval ensemble (“memory engram”)^{76–79,83–86}. b, Schematic for recording PKA activity in the CEA across familiarization using the AKAR2 sensor⁸⁷. c, Example AKAR2 expression in the CEA. d, PKA activity in the CEA in response to consumption of a novel or familiar flavor (Port A; red) and to water (Port B; blue) across four consecutive days (n = 13 mice). Points and error bars at the top of each plot indicate the timing of the next reward consumption. e, PKA activity for individual mice in response to novel or familiar flavor and to water consumption. Mice are sorted by novel flavor response (Day 1). f, Summary of PKA activity in response to novel or familiar flavor and to water consumption (n = 13 mice). g, PKA activity in response to novel flavor (left) and water (right) consumption on Day 1 for individual mice aligned to the Allen CCF (n = 13 mice). h, Schematic of a putative hypothesis linking biochemistry with neural activity during CTA, with novel flavor-dependent increases in PKA in amygdala neurons leading to increased reactivation by delayed CGRP neuron inputs and recruitment into the CTA memory retrieval ensemble. P-values in f are from GLMM marginal effect z-tests corrected for multiple comparisons across days. Error bars and shaded areas represent mean ± s.e.m. *P ≤ 0.05, ****P ≤ 0.0001, NS, not significant (P > 0.05).