A transcriptomic atlas of mouse cerebellar cortex reveals novel cell types

The cerebellar cortex is a well-studied brain structure with diverse roles in motor learning, coordination, cognition, and autonomic regulation. Nonetheless, a complete inventory of cerebellar cell types is presently lacking. We used high-throughput transcriptional profiling to profile more than 600,000 nuclei and molecularly define cell types across individual lobules of the adult mouse cerebellum. Purkinje neurons showed considerable regional specialization, with the greatest diversity occurring in the posterior lobules. For multiple types of cerebellar interneurons, the molecular variation within each type was more continuous, rather than discrete. For the unipolar brush cells (UBCs)—an interneuron population previously subdivided into discrete populations—the continuous variation in gene expression was associated with a graded continuum of electrophysiological properties. Most surprisingly, we found that molecular layer interneurons (MLIs) were composed of two molecularly and functionally distinct types. Both show a continuum of morphological variation through the thickness of the molecular layer, but electrophysiological recordings revealed marked differences between the two types in spontaneous firing, excitability, and electrical coupling. Together, these findings provide the first comprehensive cellular atlas of the cerebellar cortex, and outline a methodological and conceptual framework for the integration of molecular, morphological, and physiological ontologies for defining brain cell types. Overall design: Characterization and annotation of single nuclei transcriptomes from adult and developing mouse cerebella. Nuclei suspensions for adult mouse cerebellum profiles were generated from 2 female and 4 male adult mice (60 days old), from individual dissections across 16 regions. Nuclei suspensions for developing mouse cerebellum profiles were generated from 2 E18 mice, 2 P0 (newborn) mice, 2 P4 (4 days old) mice, 2 P8, 2 male P12 and 2 male P16 mice. >>>Raw data are unavailable for human samples due to patient privacy concerns<<<