Function and Evolution of Molecular Cell Types in the Superior Colliculus

The superior colliculus (SC) is a prominent sensorimotor hub that detects visual information, integrates multisensory signals, and transforms them into motor commands to drive reflexive and cognitive behaviors. Its superficial layer (sSC) manifests various visual responses such as direction selectivity, orientation selectivity, and motion. Traditionally, neurons in the sSC were categorized into distinct functional, morphological, connectivity types based on their similarities. Recently, with the development of single cell genomic approach, more diverse transcriptomic cell types were demonstrated in the sSC. However, it remains unclear how diverse functions are delegated among collicular transcriptomic types. Here, we identified ~30 neuronal subtypes in the mouse sSC and revealed their spatial distribution in a laminae-specific pattern. Then we developed a multi-modal approach to link functional and transcriptomic types by imaging calcium dynamics of single sSC neurons in vivo during visual stimulation and mapping marker gene transcripts onto the same neurons ex vivo. Our results revealed an inhibitory subtype that accounts for about half of the sSC’s direction selective cells, suggesting a genetic logic for the functional organization of the sSC. In addition, our studies provide a comprehensive molecular atlas of sSC neuron subtypes and a multimodal mapping method that will facilitate investigation of their respective function, connectivity, and development. The SC is well known for its conservation at the level of organization, connectivity, function, and cellular morphology, but how its gene expression and molecular cell type have evolved remain largely unknown. Using single-nucleus transcriptomics, we compared the SC’s molecular and cellular organization across mice, tree shrews, and humans. Our findings suggested that the SC has evolved by (1) harboring ~30 molecularly conserved cell types, (2) maintaining synaptic gene expression and circuitry, (3) diverging a subset of inhibitory neurons via changing its gene expression associated with synapse, and (4) enhancing the role of the primary cilium in neuronal signaling. Together, our results demonstrate that the SC evolved through distinct mechanisms compared to the neocortex, in which synaptic gene expression is the most divergent. Our results also shed light on how SC have diversified cellularly and molecularly, revealing inhibitory neuron subtypes which diverged highly during evolution and an enrichment of transcripts related to primary cilium function in higher order species.