RT Journal Article
SR Electronic
T1 A transcriptomic atlas of the mouse cerebellum reveals regional specializations and novel cell types
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.03.04.976407
DO 10.1101/2020.03.04.976407
A1 Velina Kozareva
A1 Caroline Martin
A1 Tomas Osorno
A1 Stephanie Rudolph
A1 Chong Guo
A1 Charles Vanderburg
A1 Naeem Nadaf
A1 Aviv Regev
A1 Wade Regehr
A1 Evan Macosko
YR 2020
UL http://biorxiv.org/content/early/2020/03/05/2020.03.04.976407.abstract
AB The cerebellum 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 molecularly define cell types across individual lobules of the adult mouse cerebellum. Purkinje and granule 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 two 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.