Fig. 8. The AWCOFF neuron stores the information in the parental trained generation and in their F1 descendants. In both, serotonin mediates the systemic stress response.
A Light activation of either the AWCOFF or the AWCON neurons induced the stress response in the trained P0 generation. However, in the F1 generation, light activation of the AWCOFF neuron, but not of the AWCON, induced the stress response. Exclusive inhibition of the AWCOFF neuron during IAA exposure abolished induction of the stress response in both the parental trained generation and in their F1 progeny. His, histamine added 30 min before challenging the animals with the CS IAA. B Benzaldehyde, also sensed by the AWC neurons, can be used to induce the stress response in P0 animals as well as in their F1 progeny. The P0 animals were trained to associate starvation with IAA. C Serotonin mediates the systemic stress response in trained animals and in their F1 progeny following odor-induced stress response. Exposure to exogenous serotonin (without odor) induced DAF-16/FOXO nuclear translocation. Similarly, light activation of the serotonergic neurons (ADF, NSM and HSN) induced a rapid systemic stress response in both the trained P0 worms and in their F1 descendants. In all panels, shown are the means ± SEM of N = 3–4 biologically independent experimental repeats, each scoring ∼50 animals. Significance comparisons are between trained and mock-trained animals. ***p < 0.0005. P-values from left to right: A 1.8E−15, 0.8, 3.3E−5, 1.6E−6, 7.8E−11, 0.7, 1.1E−8, 0.5 B 6.8E−8, 4.8E−6 C 0.34, 2.3E−26, 0.54, 3.4E−8, 2.8E−24, 9.2E−15 (two-sided proportion test, after Bonferroni correction). D A proposed model for inheritance of the acquired cellular changes. In the trained P0 generation, the stress response may be induced by the exclusive activation of either the AWCON or AWCOFF chemosensory neurons, suggesting that these neurons are part of the information-storing ensemble. Neuropeptides, small RNAs, and histone methylation (H3K9 and H3K36) work in concert to modulate the sperm state, and by this, transmit the acquired cellular changes to the somatic cells of the next generation. Notably, while these genes and pathways play a role in the inheritance process, these epigenetic factors are not required for acquiring and activating the cellular changes in the parental trained generation. Source data is provided as a Source Data file.