Fig. 5 |. Postingestive CGRP neuron activity induces plasticity to stabilize novel flavor representations in the amygdala upon memory retrieval.
a, Spike waveforms, autocorrelograms, and flavor response rasters for one example neuron tracked across conditioning and retrieval days. b, Heatmap showing the average spiking of all recorded neurons (n = 939 neurons from 8 mice) to novel flavor and water consumption during the consumption period (left) and during the delay and CGRP neuron stimulation periods (middle) on conditioning day, and the responses of the same neurons to flavor and water consumption on retrieval day. Neurons are grouped by their novel flavor/water preference on pairing day and then sorted by CGRP response magnitude. c, Left: Trial-average spiking of the novel flavor-preferring population (n = 265 neurons) during flavor consumption on conditioning day (black) and retrieval day (red). Middle/Right: Trial-average spiking of the novel-preferring neurons with the highest 10% of CGRP response magnitudes (High CGRP response; middle) and of the remaining novel-preferring neurons (Low CGRP response; right) on conditioning day and retrieval day. The insets show the average CGRP neuron stimulation response profile of each subpopulation. d, Correlation between each neuron’s change (Retrieval – Conditioning) in flavor response (top) or selectivity (bottom) during the consumption period to its average response during the CGRP neuron stimulation period. The novel flavor-preferring (left; n = 265 neurons), water-preferring (middle; n = 123 neurons), and non-selective (right; n = 551 neurons) populations are shown separately. e, Analogous to d, but for mice with CGRPCEA projection stimulation rather than cell-body stimulation (n = 286 novel flavor-preferring neurons from 8 mice). See Extended Data Fig. 10c–e for additional analysis. f, Left: Schematic for the flavor familiarization experiment. Right: Trial-average spiking of the initially flavor-preferring population (n = 201 neurons from 7 mice; classified on novel day) during flavor consumption on novel day (black) and familiar day (blue). The inset quantifies the average response on each day. See Extended Data Fig. 10h–k for additional analysis. g, Illustration of a neural mechanism for learning from delayed postingestive feedback using malaise-driven reactivation and stabilization of amygdala novel flavor representations. P-values in d,e are from Pearson correlation t-tests. P-value in f is from a Wilcoxon signed-rank test. Error bars represent mean ± s.e.m. Shaded areas in c,f represent mean ± s.e.m. and in d,e represent 95% confidence interval for linear fit. *P ≤ 0.05, ***P ≤ 0.001, ****P ≤ 0.0001, NS, not significant (P > 0.05).