Neuroplasticity serves as the foundation of learning and memory formation, which are indispensable to our lives. Its deficits give rise to an array of disorders, including dementia and post-traumatic stress disorder (PTSD). We will tackle on fundamental questions regarding the epigenetic and transcriptional basis of memory-encoding neuronal ensemble (e.g., engram) formation. To this end, we will employ a multidisciplinary approach that encompasses genomics, mouse genetics, circuit analysis and bioinformatics.
Our laboratory is built upon two main pillars.
We will leverage high-end epigenomics and genomics sequencing technologies to uncover molecular basis of memory-encoding neuronal ensemble formation. We will employ gene KD/OE, as well as optogenetics technologies, to evaluate functional relevance of our findings based on genomics profiles.
We will develop novel high-throughput sequencing technologies, such as whole genome history tracing, which will overcome the critical limitations of existing snapshot-type technologies. These advanced methodologies will enable us to gain insights into how heterogeneity of neuronal ensemble is generated.
Please also see our research vision regarding the ERC-StG grant (MemoPlasticGenomics).
Epigenetic and transcriptional mechanism regulating IEG inducibility in sensory neurons. t-SNE representation (left) and genome browser view (right) of epigenetic chromatin organization in neuronal activity-response genes at pre-sensory stage (E14.5). In sensory neurons, prior to sensory activity-dependent induction, immediate early genes (IEGs, e.g., Fos, Egr1) are embedded into a unique ‘bipartite' Polycomb chromatin signature. Namely, IEGs carry an active H3K27ac mark on promoters, but a repressive Polycomb-H3K27me3 mark on gene bodies, which is clearly distinct from classic Polycomb bivalent organization that is preferentially found in activity late-response genes (LRGs). Adapted from Kitazawa et al., Nature Genetics 2021.