A05 will exploit natural inter-individual variability of resilience by comparing transcriptomes and genome-wide chromatin accessibility of hippocampus, nucleus accumbens and prefrontal cortex between resilient and non-resilient mice. Next, we will apply specific inhibitors of distinct epigenetic regulators to different groups of mice at the time of stress and compare their later behavioral outcomes with non-drug treated control groups subjected to identical stress. For mice treated with the inhibitor that showed the strongest resilience-promoting effects, we will then determine transcriptomes, genome-wide chromatin accessibility and associated epigenetic marks of the above mentioned brain regions.
Domingo-Rodriguez L, Ruiz de Azua I, Dominguez E, Senabre E, Serra I, Kummer S, Navandar M, Baddenhausen S, Hofmann C, Andero R, Gerber S, Navarrete M, Dierssen M, Lutz B, Martín-García E, Maldonado R (2020) A specific prelimbic-nucleus accumbens pathway controls resilience versus vulnerability to food addiction. Nat Comm 11(1):782. doi: 10.1038/s41467-020-14458-y