In his ground-breaking book The Origin of Species, Darwin argued that struggle-for-life (e.g. prey capture and predator avoidance) is the basic form for species to adapt to their environment. Dissecting the brain circuits that initiate the innate struggle-for-life behaviors would be a critical step to understand how animals survive in the environment and how natural selection proceeds in evolution. In a series of recent studies, we identified a set of Ying-Yang circuit modules in the superior colliculus (SC) of midbrain to initiate prey capture and predator avoidance behaviors in mice (Shang et al., 2015; Shang & Chen et al., 2018; Shang, Liu, Li & Xie et al., 2019). Moreover, by using single-cell RNA-Seq technology (in collaboration with Dr. Xiaoqun Wang), we analyzed the gene expression profiles of SC neurons and identified the unique genetic markers of these circuit modules (unpublished). Such information would help us further reveal how the genes regulate the formation of hard-wired circuit modules and how the genes realize the genetically-encoded innate struggle-for-life behaviors.

In this part of research, we focus on the development of genetic mouse tools to visualize hallmarks of neurodegeneration in living animals. By combining single-cell analysis approaches with these mouse tools, we will be able to dissect the pathological effects of neurodegeneration on cell-type-specific brain circuits on single-cell level. Moreover, miniscope-aided long-term imaging of the living cells labeled by neurodegeneration tools enables us to read out how neurodegeneration progressively exerts pathological effects on brain circuits. These mouse tools will of course be shared with other laboratories in the field of neurodegeneration.