bims-climfi 2021-10-10 papers

Issue of 2021–10–10
three papers selected by
Jun Maruta, Mount Sinai Health System

Nature. 2021 Oct;598(7879): 214-219

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, Evan Macosko.

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.

DOI: https://doi.org/10.1038/s41586-021-03220-z

Nat Commun. 2021 Oct 07. 12(1): 5491

Graded heterogeneity of metabotropic signaling underlies a continuum of cell-intrinsic temporal responses in unipolar brush cells.

Chong Guo, Vincent Huson, Evan Z Macosko, Wade G Regehr.

Many neuron types consist of populations with continuously varying molecular properties. Here, we show a continuum of postsynaptic molecular properties in three types of neurons and assess the functional correlates in cerebellar unipolar brush cells (UBCs). While UBCs are generally thought to form discrete functional subtypes, with mossy fiber (MF) activation increasing firing in ON-UBCs and suppressing firing in OFF-UBCs, recent work also points to a heterogeneity of response profiles. Indeed, we find a continuum of response profiles that reflect the graded and inversely correlated expression of excitatory mGluR1 and inhibitory mGluR2/3 pathways. MFs coactivate mGluR2/3 and mGluR1 in many UBCs, leading to sequential inhibition-excitation because mGluR2/3-currents are faster. Additionally, we show that DAG-kinase controls mGluR1 response duration, and that graded DAG kinase levels correlate with systematic variation of response duration over two orders of magnitude. These results demonstrate that continuous variations in metabotropic signaling can generate a stable cell-autonomous basis for temporal integration and learning over multiple time scales.

DOI: https://doi.org/10.1038/s41467-021-22893-8

Front Syst Neurosci. 2021 ;15 752719

Editorial: Information Processing in the Cerebellum.

Conor Houghton, Philippe Isope, Richard Apps, Nadia L Cerminara.

Keywords: cerebellar circuitry; cerebellar learning; cerebellum; complex spike; computational modeling; forward model; oscillations; timing

DOI: https://doi.org/10.3389/fnsys.2021.752719