A transcriptomic atlas of mouse cerebellar cortex comprehensively defines cell types

Velina Kozareva, Caroline Martin, Tomas Osorno, Stephanie Rudolph, Chong Guo, Charles Vanderburg, Naeem Nadaf, Aviv Regev, Wade G. Regehr and Evan Macosko ()
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Velina Kozareva: Stanley Center for Psychiatric Research
Caroline Martin: Stanley Center for Psychiatric Research
Tomas Osorno: Harvard Medical School
Stephanie Rudolph: Harvard Medical School
Chong Guo: Harvard Medical School
Charles Vanderburg: Stanley Center for Psychiatric Research
Naeem Nadaf: Stanley Center for Psychiatric Research
Aviv Regev: Stanley Center for Psychiatric Research
Wade G. Regehr: Harvard Medical School
Evan Macosko: Stanley Center for Psychiatric Research

Nature, 2021, vol. 598, issue 7879, 214-219

Abstract: Abstract The cerebellar cortex is a well-studied brain structure with diverse roles in motor learning, coordination, cognition and autonomic regulation. However, a complete inventory of cerebellar cell types is currently lacking. Here, using recent advances in high-throughput transcriptional profiling1–3, we 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 several types of cerebellar interneuron, the molecular variation within each type was more continuous, rather than discrete. In particular, for the unipolar brush cells—an interneuron population previously subdivided into discrete populations—the continuous variation in gene expression was associated with a graded continuum of electrophysiological properties. Notably, we found that molecular layer interneurons were composed of two molecularly and functionally distinct types. Both types 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 a 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.

Date: 2021
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DOI: 10.1038/s41586-021-03220-z

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