Guanhua Sun, James Hazelden, Ruby Kim, Daniel B Forger
Wild type mice displayed pronounced diet-dependent adaptations that were largely missing in transgenic mice. In the brainstem, a high-fat diet increased the epigenetic age and induced a loss of DNA methylation of neuronal genes involved in protein degradation and mitochondrial metabolism-changes that were largely driven by DNA hydroxymethylation and absent in transgenic mice. Integration of methylation and gene expression data further revealed shared, and brain region-specific interaction networks implicated in metabolism, proteostatis, and neuronal pathways showing molecular adaptation specifically in wild type mice upon high-fat diet.
Traveling waves are ubiquitous in neuronal systems across different spatial scales. While microscopic and mesoscopic waves are relatively well studied, the emergence of macroscopic traveling waves remains less understood. Here, by modeling the mouse cortex using spatial transcriptomic and connectivity data, we show that realistic cortical connectivity can generate a significantly higher level of macroscopic traveling waves than artificial local and uniform connectivity across multiple oscillation frequency bands, with the strongest advantage appearing in the theta, alpha, and beta frequency bands. By probing the model in different dynamic regimes, we find that macroscopic wave activity depends on both network connectivity and excitatory coupling strength, with a non-monotonic dependence on coupling. Together, our work shows how flexible macroscopic traveling waves can emerge in the mouse cortex and offers a computational framework to further study traveling waves in the mouse brain at the single-cell level.