Connectivity of single neurons classifies cell subtypes in mouse brains

Abstract

Classification of single neurons at a brain-wide scale is a way to characterize the structural and functional organization of brains. Here we acquired and standardized a large morphology database of 20,158 mouse neurons and generated a potential connectivity map of single neurons based on their dendritic and axonal arbors. With such an anatomy–morphology–connectivity mapping, we defined neuron connectivity subtypes for neurons in 31 brain regions. We found that cell types defined by connectivity show distinct separation from each other. Within this context, we were able to characterize the diversity in secondary motor cortical neurons, and subtype connectivity patterns in thalamocortical pathways. Our findings underscore the importance of connectivity in characterizing the modularity of brain anatomy at the single-cell level. These results highlight that connectivity subtypes supplement conventionally recognized transcriptomic cell types, electrophysiological cell types and morphological cell types as factors to classify cell classes and their identities. This Resource presents a method to define connectivity types of neurons based on a spatially registered large database containing more than 20,000 neuronal reconstructions. A brain connectivity map is also generated using such connectivity features.